WO2016071706A1 - Container containing a nicotine solution - Google Patents

Container containing a nicotine solution Download PDF

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Publication number
WO2016071706A1
WO2016071706A1 PCT/GB2015/053369 GB2015053369W WO2016071706A1 WO 2016071706 A1 WO2016071706 A1 WO 2016071706A1 GB 2015053369 W GB2015053369 W GB 2015053369W WO 2016071706 A1 WO2016071706 A1 WO 2016071706A1
Authority
WO
WIPO (PCT)
Prior art keywords
nicotine
acid
solution
container
protonated
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.)
Ceased
Application number
PCT/GB2015/053369
Other languages
English (en)
French (fr)
Inventor
Kevin Gerard Mcadam
Connor BRUTON
Marina Trani
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.)
Nicoventures Holdings Ltd
Original Assignee
Nicoventures Holdings Ltd
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=52118166&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2016071706(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority to MYPI2017701451A priority Critical patent/MY198202A/en
Priority to EP20183945.3A priority patent/EP3738447B1/en
Priority to KR1020197014770A priority patent/KR102035196B1/ko
Priority to BR112017009258-1A priority patent/BR112017009258B1/pt
Priority to US15/525,163 priority patent/US20180228214A1/en
Priority to CA2964829A priority patent/CA2964829C/en
Priority to RU2017115501A priority patent/RU2677847C2/ru
Priority to AU2015341517A priority patent/AU2015341517B2/en
Priority to MX2017005939A priority patent/MX2017005939A/es
Priority to KR1020177012228A priority patent/KR101984834B1/ko
Priority to EP24192713.6A priority patent/EP4430961A3/en
Application filed by Nicoventures Holdings Ltd filed Critical Nicoventures Holdings Ltd
Priority to ES15794254T priority patent/ES2718222T3/es
Priority to CN201580060720.XA priority patent/CN107072287B/zh
Priority to CN201910110391.5A priority patent/CN109965357B/zh
Priority to JP2017523310A priority patent/JP6450002B2/ja
Priority to EP18212381.0A priority patent/EP3491941B1/en
Priority to EP15794254.1A priority patent/EP3214957B1/en
Priority to PL15794254T priority patent/PL3214957T3/pl
Priority to PH1/2020/500540A priority patent/PH12020500540A1/en
Priority to UAA201704357A priority patent/UA122864C2/uk
Priority to PL18212381T priority patent/PL3491941T3/pl
Publication of WO2016071706A1 publication Critical patent/WO2016071706A1/en
Priority to PH12017500837A priority patent/PH12017500837A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24F—SMOKERS' REQUISITES; MATCH BOXES; SIMULATED SMOKING DEVICES
    • A24F40/00—Electrically operated smoking devices; Component parts thereof; Manufacture thereof; Maintenance or testing thereof; Charging means specially adapted therefor
    • A24F40/40—Constructional details, e.g. connection of cartridges and battery parts
    • A24F40/42—Cartridges or containers for inhalable precursors
    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
    • A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
    • A24B15/10—Chemical features of tobacco products or tobacco substitutes
    • A24B15/16—Chemical features of tobacco products or tobacco substitutes of tobacco substitutes
    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
    • A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
    • A24B15/10—Chemical features of tobacco products or tobacco substitutes
    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
    • A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
    • A24B15/10—Chemical features of tobacco products or tobacco substitutes
    • A24B15/16—Chemical features of tobacco products or tobacco substitutes of tobacco substitutes
    • A24B15/167—Chemical features of tobacco products or tobacco substitutes of tobacco substitutes in liquid or vaporisable form, e.g. liquid compositions for electronic cigarettes
    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
    • A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
    • A24B15/18—Treatment of tobacco products or tobacco substitutes
    • A24B15/28—Treatment of tobacco products or tobacco substitutes by chemical substances
    • A24B15/30—Treatment of tobacco products or tobacco substitutes by chemical substances by organic substances
    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24F—SMOKERS' REQUISITES; MATCH BOXES; SIMULATED SMOKING DEVICES
    • A24F40/00—Electrically operated smoking devices; Component parts thereof; Manufacture thereof; Maintenance or testing thereof; Charging means specially adapted therefor
    • A24F40/10—Devices using liquid inhalable precursors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/465—Nicotine; Derivatives thereof
    • 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
    • A61M15/06—Inhaling appliances shaped like cigars, cigarettes or pipes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2023/00—Use of polyalkenes or derivatives thereof as moulding material
    • B29K2023/10—Polymers of propylene
    • B29K2023/12—PP, i.e. polypropylene
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2069/00—Use of PC, i.e. polycarbonates or derivatives thereof, as moulding material
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29L—INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES
    • B29L2031/00—Other particular articles
    • B29L2031/712—Containers; Packaging elements or accessories, Packages
    • B29L2031/7142—Aerosol containers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29L—INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES
    • B29L2031/00—Other particular articles
    • B29L2031/7414—Smokers'' requisites, e.g. pipe cleaners
    • B29L2031/7416—Smokers'' requisites, e.g. pipe cleaners for cigars or cigarettes

Definitions

  • the present disclosure relates to containers which contain a nicotine solution and to electronic vapour provision systems such as electronic nicotine delivery systems (e.g. e- cigarettes) incorporating such containers.
  • electronic nicotine delivery systems e.g. e- cigarettes
  • Electronic vapour provision systems such as e-cigarettes generally contain a reservoir of liquid which is to be vaporised, typically containing nicotine.
  • a heater is activated to vaporise a small amount of liquid, which is therefore inhaled by the user.
  • the liquid to be vaporised in e-cigarettes is typically a solution containing nicotine.
  • the solvent may be, for example, glycerol.
  • the vaporising part of the device is often designed for multiple uses, although single use devices do exist. In multiple and single use devices a container holding the nicotine solution is present. The container is stored for significant periods from the time of filling until use. This period includes the time of distribution, stocking by a retailer and storage by the end user before use. During this storage period, loss of nicotine content may occur.
  • a contained nicotine solution comprising
  • the container in contact with the nicotine solution is formed from polycarbonate or polypropylene.
  • an electronic vapour provision system comprising:
  • a vaporiser for vaporising liquid for inhalation by a user of the electronic vapour provision system
  • a power supply comprising a cell or battery for supplying power to the vaporiser a container in which is contained a nicotine solution, wherein at least 5 wt% of the nicotine present in the solution is in protonated form, and wherein at least a portion of the container in contact with the nicotine solution is formed from polycarbonate or polypropylene.
  • a process for stabilising a nicotine solution comprising the steps of protonating the nicotine present in the solution such that at least 5 wt% of the nicotine present in the solution is in protonated form.
  • the present disclosure relates to a container which may be used in an electronic vapour provision system, such as an e-cigarette.
  • an electronic vapour provision system such as an e-cigarette.
  • nicotine may exist in free base form, monoprotonated form or diprotonated form.
  • monoprotonated form may exist in free base form, monoprotonated form or diprotonated form.
  • the structures of each of these forms are given below.
  • Reference in the specification to protonated form means both monoprotonated nicotine and diprotonated nicotine. Reference in the specification to amounts in the protonated form means the combined amount of monoprotonated nicotine and diprotonated nicotine.
  • the present invention provides a container in which is contained a nicotine solution, wherein at least 5 wt% of the nicotine present in the solution is in protonated form, wherein at least a portion of the container in contact with the nicotine solution is formed from polycarbonate or polypropylene.
  • a nicotine solution wherein at least 5 wt% of the nicotine present in the solution is in protonated form, wherein at least a portion of the container in contact with the nicotine solution is formed from polycarbonate or polypropylene.
  • the relevant amounts of nicotine which are present in the solution in protonated form are specified herein. These amounts may be readily calculated by one skilled in the art.
  • Nicotine 3-(1-methylpyrrolidin-2-yl) pyridine, is a diprotic base with pKa of 3.12 for the pyridine ring and 8.02 for the pyrrolidine ring. It can exist in pH-dependent protonated (mono- and di-) and non-protonated forms which have different bioavailability.
  • the fraction of non-protonated nicotine will be predominant at high pH levels whilst a decrease in the pH will see an increase of the fraction of protonated nicotine (mono- or di- depending on the pH). If the relative fraction of protonated nicotine and the total amount of nicotine in the sample are known, the absolute amount of protonated nicotine can be calculated.
  • the relative fraction of protonated nicotine in solution can be calculated by using the Henderson-Hasselbalch equation, which describes the pH as a derivation of the acid dissociation constant equation, and it is extensively employed in chemical and biological systems.
  • [B] is the amount of non-protonated nicotine (i.e. free base)
  • [BH+] the amount of protonated nicotine (i.e. conjugate acid)
  • the relative fraction of protonated nicotine can be derived from the alpha value of the non-protonated nicotine calculated from the Henderson-Hasselbalch equation as:
  • At least a portion of the container in contact with the nicotine solution is formed from polycarbonate. In one aspect the majority of the container which is in contact with the nicotine solution is formed from polycarbonate. In one aspect all the container which is in contact with the nicotine solution is formed from polycarbonate. In one aspect the container is formed entirely from polycarbonate.
  • polypropylene it is meant a polymer containing the following repeating unit
  • At least a portion of the container in contact with the nicotine solution is formed from polypropylene.
  • the majority of the container which is in contact with the nicotine solution is formed from polypropylene.
  • all the container which is in contact with the nicotine solution is formed from polypropylene.
  • the container is formed entirely from polypropylene.
  • the majority of the container which is in contact with the nicotine solution is formed from polycarbonate, polypropylene or a combination thereof.
  • all the container which is in contact with the nicotine solution is formed from polycarbonate, polypropylene or a combination thereof.
  • the container is formed entirely from polycarbonate, polypropylene or a combination thereof.
  • the container of the present invention is typically provided for the delivery of nicotine solution to or within an e-cigarette.
  • the nicotine solution may be held within an e-cigarette or may be sold as a separate container for subsequent use with or in an e-cigarette.
  • e-cigarettes typically contain a unit known as a cartomiser which comprises a reservoir of nicotine solution, a wick material and a heating element for vaporising the nicotine.
  • the container is a cartomiser or is part of a cartomiser.
  • the container is not a cartomiser or part of a cartomiser and is a container, such as a tank, bottle or the like, which may be used to deliver nicotine solution to or within an e-cigarette.
  • the container is part of an e-cigarette. Therefore in a further aspect the present invention provides an electronic vapour provision system comprising: a vaporiser for vaporising liquid for inhalation by a user of the electronic vapour provision system; a power supply comprising a cell or battery for supplying power to the vaporiser; a container in which is contained a nicotine solution, wherein at least 5 wt% of the nicotine present in the solution is in protonated form, and wherein at least a portion of the container in contact with the nicotine solution is formed from polycarbonate or polypropylene.
  • contact may occur between the container and the nicotine solution by any means. Provided the body of the container is contacted with nicotine solution then the container and solution are in contact. It is envisaged that the nicotine solution could be 'free' in the sense that it is a liquid in direct contact with the walls of the container. In also envisaged, that the nicotine solution may be held within a matrix (such as a foam) and the foam is in contact with the body of the container.
  • a matrix such as a foam
  • the nicotine present in the solution is in protonated form. In one aspect at least 15 wt% of the nicotine present in the solution is in protonated form. In one aspect at least 20 wt% of the nicotine present in the solution is in protonated form. In one aspect at least 25 wt% of the nicotine present in the solution is in protonated form. In one aspect at least 30 wt% of the nicotine present in the solution is in protonated form. In one aspect at least 35 wt% of the nicotine present in the solution is in protonated form.
  • At least 40 wt% of the nicotine present in the solution is in protonated form. In one aspect at least 45 wt% of the nicotine present in the solution is in protonated form. In one aspect at least 50 wt% of the nicotine present in the solution is in protonated form. In one aspect at least 55 wt% of the nicotine present in the solution is in protonated form. In one aspect at least 60 wt% of the nicotine present in the solution is in protonated form. In one aspect at least 65 wt% of the nicotine present in the solution is in protonated form. In one aspect at least 70 wt% of the nicotine present in the solution is in protonated form. In one aspect at least 75 wt% of the nicotine present in the solution is in protonated form.
  • At least 80 wt% of the nicotine present in the solution is in protonated form. In one aspect at least 85 wt% of the nicotine present in the solution is in protonated form. In one aspect at least 90 wt% of the nicotine present in the solution is in protonated form. In one aspect at least 95 wt% of the nicotine present in the solution is in protonated form. In one aspect at least 99 wt% of the nicotine present in the solution is in protonated form.
  • the nicotine protonation may be provided in such a manner to achieve the desired degree of protonation of nicotine.
  • the nicotine is protonated by an organic acid.
  • the nicotine is protonated by a carboxylic acid.
  • the carboxylic acid may be any suitable carboxylic acid.
  • the nicotine is protonated by a mono-carboxylic acid. In one aspect the nicotine is protonated by an acid selected from the group consisting of acetic acid, lactic acid, formic acid, citric acid, benzoic acid, pyruvic acid, levulinic acid, succinic acid, tartaric acid, oleic acid, sorbic acid, propionic acid, phenylacetic acid, and mixtures thereof. In one aspect the nicotine is protonated by an acid selected from the group consisting of benzoic acid, levulinic acid, and mixtures thereof. In one aspect the nicotine is protonated by levulinic acid. In one aspect the nicotine is protonated by benzoic acid. In one aspect the nicotine is protonated by a mixture of levulinic acid and benzoic acid. Nicotine may exist in free base form, monoprotonated form or diprotonated form.
  • the present invention therefore provides a novel process for stabilising a nicotine solution.
  • the present invention provides a process for stabilising a nicotine solution, the process comprising the steps of protonating the nicotine present in the solution such that at least 5 wt% of the nicotine present in the solution is in protonated form.
  • the nicotine solution may be in contact with polycarbonate or polypropylene.
  • the process provides for storage of the nicotine solution in contact with polycarbonate or polypropylene for a period of at least 7 days.
  • the process provides for storage of the nicotine solution in contact with polycarbonate or polypropylene for a period of at least 14 days.
  • the process provides for storage of the nicotine solution in contact with polycarbonate or polypropylene for a period of at least 21 days.
  • the process provides for storage of the nicotine solution in contact with polycarbonate or polypropylene for a period of at least 28 days.
  • the process provides for storage of the nicotine solution in contact with polycarbonate or polypropylene for a period of at least 2 months. In one aspect the process provides for storage of the nicotine solution in contact with polycarbonate or polypropylene for a period of at least 3 months. In one aspect the process provides for storage of the nicotine solution in contact with polycarbonate or polypropylene for a period of at least 4 months. In one aspect the process provides for storage of the nicotine solution in contact with polycarbonate or polypropylene for a period of at least 5 months. In one aspect the process provides for storage of the nicotine solution in contact with polycarbonate or polypropylene for a period of at least 6 months.
  • the present invention further provides a novel use for stabilising a nicotine solution.
  • the present invention provides use of protonation of nicotine for stabilising a nicotine solution.
  • the present invention provides use of protonation of nicotine for improving storage stability of a nicotine solution.
  • the present invention provides use of protonation of nicotine for reducing evaporative loss of nicotine from a nicotine solution.
  • the present invention provides use of protonated nicotine for stabilising a solution containing nicotine free base. In one aspect the present invention provides use of protonated nicotine for improving storage stability of a solution containing nicotine free base. In one aspect the present invention provides use of protonated nicotine for reducing evaporative loss of nicotine from a nicotine free base solution. It will be understood that by 'nicotine free base solution' it may be meant a solution containing nicotine free base and protonated nicotine in an amount as described herein.
  • the present invention provides use of an acid for stabilising a nicotine solution. In one aspect the present invention provides use of an acid for improving storage stability of a nicotine solution.
  • the acid is an organic acid. In one aspect of use in accordance with the present invention the acid is a carboxylic acid. In one aspect of use in accordance with the present invention the acid is a mono-carboxylic acid.
  • the acid is selected from the group consisting of acetic acid, lactic acid, formic acid, citric acid, benzoic acid, pyruvic acid, levulinic acid, succinic acid, tartaric acid, oleic acid, sorbic acid, propionic acid, phenylacetic acid, and mixtures thereof.
  • the acid is selected from the group consisting of benzoic acid, levulinic acid, and mixtures thereof.
  • the acid is levulinic acid.
  • the acid is benzoic acid.
  • the acid is a mixture of levulinic acid and benzoic acid.
  • the present invention provides use of an acid for stabilising a nicotine solution, wherein the acid is selected from the group consisting of benzoic acid, levulinic acid, and mixtures thereof.
  • the present invention provides use of an acid for improving storage stability of a nicotine solution, wherein the acid is selected from the group consisting of benzoic acid, levulinic acid, and mixtures thereof.
  • the present invention provides use of an acid for reducing evaporative loss of nicotine from a nicotine solution, wherein the acid is selected from the group consisting of benzoic acid, levulinic acid, and mixtures thereof.
  • At least 5 wt% of the nicotine present in the nicotine solution may be in protonated form.
  • the present invention provides use of protonation of nicotine for stabilising a nicotine solution with respect to polycarbonate or polypropylene. In one aspect the present invention provides use of protonation of nicotine for improving storage stability of a nicotine solution with respect to polycarbonate or polypropylene.
  • Figure 1 shows a graph
  • a range of glycerol/water/nicotine solutions were prepared, with the water concentration fixed at 9%, the nicotine concentration varying from 30 ⁇ g/ml to 3mg/ml; and the glycerol content comprising the remainder of the solutions.
  • Simultaneous UV & CD spectra of glycerol/s-nicotine/water solutions were measured on the Applied Photophysics Ltd (Leatherhead, UK) Chiracsan Plus spectrometer. The UV absorbance & CD spectra were measured between 300-200 nm region, with various pathlengths depending upon the nicotine concentration of the solution - 10mm, 5mm, 2mm, 1 mm, 0.5mm, 0.1mm and 0.01 mm pathlengths.
  • Example 1 Based on the pKa of 7.26 determined in Example 1 , the percentage of nicotine that was protonated was calculated using the Henderson-Hasselbalch equation. The results obtained are tabulated below.
  • N/N-H Nicotine/Protonated nicotine PG: propylene glycol
  • the absorption of nicotine by a number of materials suitable for use in e-cigarettes was studied. The objective of this study was to determine whether there was any absorption of nicotine from a liquid formulation into a variety of materials occurring over time. 5g of a nicotine solution comprising 3.7 wt% nicotine, 9% water and 87.3% glycerol was loaded into 40ml amber glass vials. Pieces of polypropylene and polycarbonate were added to solutions (except for control samples), the vials were sealed with screw caps and stored in an at ambient temperatures or at 40°C in an oven for a period of eight weeks. Sampling was performed on day 1 , then at 1 week, 2 weeks, 4 weeks and 8 weeks.
  • polypropylene (PP) and polycarbonate (PC) both of which are desirable materials for use in e-cigarettes were found to result in significant loss of nicotine when stored in contact with a nicotine solution containing nicotine only in free base form.
  • the effect on storage stability of protonating nicotine was studied by examining 3 nicotine solutions loaded into cartomizer e-cigarettes ("Device") containing PP and PC.
  • the three nicotine solutions were an acid free nicotine solution and two protonated solutions, one protonated with 1.0 Molar equivalent levulinic acid and one protonated with 1.0 Molar equivalent benzoic acid.
  • a 2.5% w/w nicotine amount was used, together with 9% water and sufficient glycerol to make the solution to 100%.
  • the stability protocol incorporated filling a series of e-cigarettes for each formulation, as well as loading a number of sealed glass vials (used as control samples) to understand the source of any observed nicotine losses.
  • e-liquids approximately 100 ⁇ liquid was extracted into 20 ml extraction solvent and analysed as described for aerosol determination.
  • the e-cigarettes were puffed on a 20-channel linear smoking machine (SM450) compliant with ISO 3308, but using the following puffing parameters: 80ml puff volume, 3 second puff duration and 30 second interpuff interval.
  • SM450 20-channel linear smoking machine
  • Each port of the smoking engine was fitted with a holder containing a Cambridge filter (CF) pad to trap particulate matter.
  • TPM was determined as the weight difference of the CF before and after puffing, in accordance with ISO 4387.
  • the CF pad containing trapped aerosol was extracted into 20 ml high purity propan-2-ol containing appropriate internal standards. Nicotine and water were determined by GC analysis containing combined FID/TCD detectors. The data below reports the nicotine levels measured.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Epidemiology (AREA)
  • Toxicology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Feeding, Discharge, Calcimining, Fusing, And Gas-Generation Devices (AREA)
  • Filling, Topping-Up Batteries (AREA)
  • Manufacture Of Tobacco Products (AREA)
PCT/GB2015/053369 2014-11-07 2015-11-06 Container containing a nicotine solution Ceased WO2016071706A1 (en)

Priority Applications (22)

Application Number Priority Date Filing Date Title
CN201580060720.XA CN107072287B (zh) 2014-11-07 2015-11-06 盛装尼古丁溶液的容器
ES15794254T ES2718222T3 (es) 2014-11-07 2015-11-06 Recipiente que contiene una solución de nicotina
KR1020197014770A KR102035196B1 (ko) 2014-11-07 2015-11-06 전자 증기 공급 시스템
BR112017009258-1A BR112017009258B1 (pt) 2014-11-07 2015-11-06 Sistema eletrônico de fornecimento de vapor e cartomizador para o mesmo
US15/525,163 US20180228214A1 (en) 2014-11-07 2015-11-06 Container containing a nicotine solution
CA2964829A CA2964829C (en) 2014-11-07 2015-11-06 Electronic vapour provision system and cartomiser therefor having a container of protonated nicotine solution
RU2017115501A RU2677847C2 (ru) 2014-11-07 2015-11-06 Контейнер, содержащий раствор никотина
AU2015341517A AU2015341517B2 (en) 2014-11-07 2015-11-06 Container containing a nicotine solution
MX2017005939A MX2017005939A (es) 2014-11-07 2015-11-06 Recipiente.
KR1020177012228A KR101984834B1 (ko) 2014-11-07 2015-11-06 니코틴 용액을 함유하는 용기
EP24192713.6A EP4430961A3 (en) 2014-11-07 2015-11-06 Electronic vapour provision system
MYPI2017701451A MY198202A (en) 2014-11-07 2015-11-06 Container containing a nicotine solution
PH1/2020/500540A PH12020500540A1 (en) 2014-11-07 2015-11-06 Electronic vapour provision system
PL18212381T PL3491941T3 (pl) 2014-11-07 2015-11-06 Elektroniczny układ dostarczania pary
PL15794254T PL3214957T3 (pl) 2014-11-07 2015-11-06 Pojemnik zawierający roztwór nikotyny
JP2017523310A JP6450002B2 (ja) 2014-11-07 2015-11-06 ニコチン溶液を含む容器
EP18212381.0A EP3491941B1 (en) 2014-11-07 2015-11-06 Electronic vapour provision system
EP15794254.1A EP3214957B1 (en) 2014-11-07 2015-11-06 Container containng a nicotine solution
CN201910110391.5A CN109965357B (zh) 2014-11-07 2015-11-06 电子蒸汽提供系统
EP20183945.3A EP3738447B1 (en) 2014-11-07 2015-11-06 Electronic vapour provision system
UAA201704357A UA122864C2 (uk) 2014-11-07 2015-11-06 Контейнер, що містить розчин нікотину
PH12017500837A PH12017500837A1 (en) 2014-11-07 2017-05-05 Container containing a nicotine solution

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