US20180228214A1 - Container containing a nicotine solution - Google Patents

Container containing a nicotine solution Download PDF

Info

Publication number
US20180228214A1
US20180228214A1 US15/525,163 US201515525163A US2018228214A1 US 20180228214 A1 US20180228214 A1 US 20180228214A1 US 201515525163 A US201515525163 A US 201515525163A US 2018228214 A1 US2018228214 A1 US 2018228214A1
Authority
US
United States
Prior art keywords
nicotine
acid
solution
protonated
container
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.)
Pending
Application number
US15/525,163
Other languages
English (en)
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 Trading 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=US20180228214(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Nicoventures Holdings Ltd filed Critical Nicoventures Holdings Ltd
Assigned to NICOVENTURES HOLDINGS LIMITED reassignment NICOVENTURES HOLDINGS LIMITED ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BRUTON, Connor, MCADAM, KEVIN GERARD, TRANI, MARINA
Publication of US20180228214A1 publication Critical patent/US20180228214A1/en
Assigned to Nicoventures Trading Limited reassignment Nicoventures Trading Limited ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: NICOVENTURES HOLDINGS LIMITED
Pending legal-status Critical Current

Links

Images

Classifications

    • A24F47/008—
    • 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 vapor provision systems such as electronic nicotine delivery systems (e.g. e-cigarettes) incorporating such containers.
  • electronic nicotine delivery systems e.g. e-cigarettes
  • Electronic vapor provision systems such as e-cigarettes generally contain a reservoir of liquid which is to be vaporized, typically containing nicotine.
  • a heater is activated to vaporize a small amount of liquid, which is therefore inhaled by the user.
  • the liquid to be vaporized in e-cigarettes is typically a solution containing nicotine.
  • the solvent may be, for example, glycerol.
  • the vaporizing 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: (i) a container; and (ii) a nicotine solution contained within the container, 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.
  • an electronic vapor provision system comprising: a vaporizer for vaporizing liquid for inhalation by a user of the electronic vapor provision system; a power supply comprising a cell or battery for supplying power to the vaporizer; 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 stabilizing a nicotine solution comprising: protonating the nicotine present in the solution such that at least 5 wt % of the nicotine present in the solution is in protonated form.
  • FIG. 1 shows a graph
  • the present disclosure relates to a container which may be used in an electronic vapor provision system, such as an e-cigarette.
  • an electronic vapor provision system such as an e-cigarette.
  • e-cigarette is used; however, this term may be used interchangeably with electronic vapor provision system.
  • 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 disclosure 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.
  • Nicotine 3-(1-methylpyrrolidin-2-yl) pyridine
  • pKa 3.12 for the pyridine ring
  • 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:
  • Determination of pKa values of nicotine solutions may be was carried out using the basic approach described in “Spectroscopic investigations into the acid-base properties of nicotine at different temperatures”, Peter M. Clayton, Carl A. Vas, Tam T. T. Bui, Alex F. Drake and Kevin McAdam, .Anal. Methods, 2013, 5, 81-88. This method is summarized below.
  • polycarbonate 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 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. In one aspect the majority of the container which is in contact with the nicotine solution is formed from polypropylene. In one aspect all the container which is in contact with the nicotine solution is formed from polypropylene. In one aspect 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. In one aspect all the container which is in contact with the nicotine solution is formed from polycarbonate, polypropylene or a combination thereof. In one aspect the container is formed entirely from polycarbonate, polypropylene or a combination thereof.
  • the container of the present disclosure 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 cartomizer which comprises a reservoir of nicotine solution, a wick material and a heating element for vaporizing the nicotine.
  • the container is a cartomizer or is part of a cartomizer.
  • the container is not a cartomizer or part of a cartomizer 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 disclosure provides an electronic vapor provision system comprising: a vaporizer for vaporizing liquid for inhalation by a user of the electronic vapor provision system; a power supply comprising a cell or battery for supplying power to the vaporizer; 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.
  • At least 35 wt % of the nicotine present in the solution is in protonated form. In one aspect 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.
  • 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. In one aspect 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.
  • 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.
  • 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.
  • 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. As discussed herein we have found that by protonating at least some of the nicotine present in a solution, the stability of the nicotine solution may be enhanced. We have found that solutions of nicotine when stored for significant periods suffer loss of nicotine content. Although problems of stability are particularly observed when nicotine solution is stored in contact with polycarbonate or polypropylene, the problems are not exclusive to those materials.
  • the present disclosure therefore provides a novel process for stabilizing a nicotine solution.
  • the present disclosure provides a process for stabilizing 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. In one aspect the process provides for storage of the nicotine solution in contact with polycarbonate or polypropylene for a period of at least 14 days. In one aspect the process provides for storage of the nicotine solution in contact with polycarbonate or polypropylene for a period of at least 21 days. In one aspect the process provides for storage of the nicotine solution in contact with polycarbonate or polypropylene for a period of at least 28 days. In one aspect the process provides for storage of the nicotine solution in contact with polycarbonate or polypropylene for a period of at least 2 months.
  • 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 disclosure further provides a novel use for stabilizing a nicotine solution.
  • the present disclosure provides use of protonation of nicotine for stabilizing a nicotine solution.
  • the present disclosure provides use of protonation of nicotine for improving storage stability of a nicotine solution.
  • the present disclosure provides use of protonation of nicotine for reducing evaporative loss of nicotine from a nicotine solution.
  • the present disclosure provides use of protonated nicotine for stabilizing a solution containing nicotine free base. In one aspect the present disclosure provides use of protonated nicotine for improving storage stability of a solution containing nicotine free base. In one aspect the present disclosure 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 disclosure provides use of an acid for stabilizing a nicotine solution. In one aspect the present disclosure 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 disclosure the acid is a carboxylic acid. In one aspect of use in accordance with the present disclosure 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 disclosure provides use of an acid for stabilizing a nicotine solution, wherein the acid is selected from the group consisting of benzoic acid, levulinic acid, and mixtures thereof.
  • the present disclosure 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 disclosure 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 disclosure provides use of protonation of nicotine for stabilizing a nicotine solution with respect to polycarbonate or polypropylene. In one aspect the present disclosure provides use of protonation of nicotine for improving storage stability of a nicotine solution with respect to polycarbonate or polypropylene.
  • UV absorbance & CD spectra were measured between 300-200 nm region, with various pathlengths depending upon the nicotine concentration of the solution—10 mm, 5 mm, 2 mm, 1 mm, 0.5 mm, 0.1 mm and 0.01 mm pathlengths.
  • the instrument was flushed continuously with pure evaporated nitrogen throughout the measurements. Throughout measurements spectra were recorded with a 0.5 nm step size, a 1 s measurement time-per-point and a spectral bandwidth of 2 nm. Where possible, all CD spectra were smoothed with a window factor of 4 using the Savitzky-Golay method for better presentation.
  • Solutions of S-Nicotine in glycerol/water were pH titrated at 23° C. The pH of these solutions was raised towards alkaline by adding small aliquots of NaOH ( ⁇ pH10) and then lowered to pH2 by adding small aliquots of HCl. A series of 0.1M, 0.5M, 1M, 5M and 10M of HCl and NaOH solutions were used during the pH titration. pHs were measured at 23° C. using a Corning pH105 pH meter with a RMS pH electrode. The p s K a2 values changed systematically with nicotine concentration ( FIG. 1 ) and therefore values for p s K a2 were calculated at each nicotine concentration level (Table 1).
  • Use of this p s K a2 value with the Henderson-Hasselbalch equation allows calculation of the degree of nicotine protonationm at any pH value.
  • Example 1 The materials were formulated as described and the pH determined as described in 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.
  • 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.
  • 5 g of a nicotine solution comprising 3.7 wt % nicotine, 9% water and 87.3% glycerol was loaded into 40m1 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 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.
  • the e-cigarettes were puffed on a 20-channel linear smoking machine (SM450) compliant with ISO 3308, but using the following puffing parameters: 80 ml 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.

Landscapes

  • 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)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pulmonology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Toxicology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Manufacture Of Tobacco Products (AREA)
  • Filling, Topping-Up Batteries (AREA)
US15/525,163 2014-11-07 2015-11-06 Container containing a nicotine solution Pending US20180228214A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB1419866.7A GB2532062A (en) 2014-11-07 2014-11-07 Container
GB1419866.7 2014-11-07
PCT/GB2015/053369 WO2016071706A1 (en) 2014-11-07 2015-11-06 Container containing a nicotine solution

Publications (1)

Publication Number Publication Date
US20180228214A1 true US20180228214A1 (en) 2018-08-16

Family

ID=52118166

Family Applications (1)

Application Number Title Priority Date Filing Date
US15/525,163 Pending US20180228214A1 (en) 2014-11-07 2015-11-06 Container containing a nicotine solution

Country Status (20)

Country Link
US (1) US20180228214A1 (pl)
EP (3) EP3491941B1 (pl)
JP (1) JP6450002B2 (pl)
KR (2) KR101984834B1 (pl)
CN (2) CN109965357B (pl)
AR (2) AR102579A1 (pl)
AU (1) AU2015341517B2 (pl)
BR (1) BR112017009258B1 (pl)
CA (1) CA2964829C (pl)
CL (1) CL2017001137A1 (pl)
ES (2) ES2718222T3 (pl)
GB (1) GB2532062A (pl)
HU (2) HUE044286T2 (pl)
MX (2) MX2017005939A (pl)
MY (1) MY198202A (pl)
PH (1) PH12017500837B1 (pl)
PL (2) PL3214957T3 (pl)
RU (2) RU2677847C2 (pl)
TR (1) TR201904005T4 (pl)
WO (1) WO2016071706A1 (pl)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021035103A1 (en) * 2019-02-15 2021-02-25 Bn Intellectual Properties, Inc. Nicotine formulation for active mesh nebulizer
WO2022180491A1 (en) * 2021-02-24 2022-09-01 Rai Strategic Holdings, Inc. Aerosol precursor formulations
US11588287B2 (en) 2018-10-12 2023-02-21 Rai Strategic Holdings, Inc. Aerosol delivery device with improved connectivity, airflow, and aerosol paths
US11583003B2 (en) 2018-10-12 2023-02-21 Rai Strategic Holdings, Inc. Connectors for forming electrical and mechanical connections between interchangeable units in an aerosol delivery system
US11678700B2 (en) 2018-10-12 2023-06-20 Rai Strategic Holdings, Inc. Aerosol delivery device with visible indicator
US11974603B2 (en) 2018-10-12 2024-05-07 Rai Strategic Holdings, Inc. Aerosol delivery device with visible indicator

Families Citing this family (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10244793B2 (en) 2005-07-19 2019-04-02 Juul Labs, Inc. Devices for vaporization of a substance
US8991402B2 (en) 2007-12-18 2015-03-31 Pax Labs, Inc. Aerosol devices and methods for inhaling a substance and uses thereof
US10279934B2 (en) 2013-03-15 2019-05-07 Juul Labs, Inc. Fillable vaporizer cartridge and method of filling
CN114223928A (zh) 2013-05-06 2022-03-25 尤尔实验室有限公司 用于气溶胶装置的烟碱盐调配物及其方法
KR102328024B1 (ko) 2013-12-05 2021-11-17 쥴 랩스, 인크. 에어로졸 장치를 위한 니코틴 액제 및 그 방법
US20160366947A1 (en) 2013-12-23 2016-12-22 James Monsees Vaporizer apparatus
US10076139B2 (en) 2013-12-23 2018-09-18 Juul Labs, Inc. Vaporizer apparatus
US10159282B2 (en) 2013-12-23 2018-12-25 Juul Labs, Inc. Cartridge for use with a vaporizer device
USD825102S1 (en) 2016-07-28 2018-08-07 Juul Labs, Inc. Vaporizer device with cartridge
US10058129B2 (en) 2013-12-23 2018-08-28 Juul Labs, Inc. Vaporization device systems and methods
USD842536S1 (en) 2016-07-28 2019-03-05 Juul Labs, Inc. Vaporizer cartridge
CN110638109B (zh) 2013-12-23 2023-08-18 尤尔实验室有限公司 蒸发装置系统和方法
US9549573B2 (en) 2013-12-23 2017-01-24 Pax Labs, Inc. Vaporization device systems and methods
CA2948851A1 (en) 2014-05-16 2015-11-19 Pax Labs, Inc. Systems and methods for aerosolizing a smokeable material
CN113754634A (zh) 2014-05-27 2021-12-07 R.J.雷诺兹烟草公司 烟碱盐、共晶体和盐共晶体络合物
US9896429B2 (en) 2014-05-27 2018-02-20 R.J. Reynolds Tobacco Company Nicotine salts, co-crystals, and salt co-crystal complexes
US10508096B2 (en) 2014-05-27 2019-12-17 R.J. Reynolds Tobacco Company Nicotine salts, co-crystals, and salt co-crystal complexes
GB2535427A (en) 2014-11-07 2016-08-24 Nicoventures Holdings Ltd Solution
GB2532062A (en) 2014-11-07 2016-05-11 Nicoventures Holdings Ltd Container
CN112155255A (zh) 2014-12-05 2021-01-01 尤尔实验室有限公司 校正剂量控制
CO2018009342A2 (es) 2016-02-11 2018-09-20 Juul Labs Inc Cartuchos de fijación segura para dispositivos vaporizadores
SG11201806793TA (en) 2016-02-11 2018-09-27 Juul Labs Inc Fillable vaporizer cartridge and method of filling
US10405582B2 (en) 2016-03-10 2019-09-10 Pax Labs, Inc. Vaporization device with lip sensing
USD849996S1 (en) 2016-06-16 2019-05-28 Pax Labs, Inc. Vaporizer cartridge
USD848057S1 (en) 2016-06-23 2019-05-07 Pax Labs, Inc. Lid for a vaporizer
USD836541S1 (en) 2016-06-23 2018-12-25 Pax Labs, Inc. Charging device
USD851830S1 (en) 2016-06-23 2019-06-18 Pax Labs, Inc. Combined vaporizer tamp and pick tool
US11660403B2 (en) 2016-09-22 2023-05-30 Juul Labs, Inc. Leak-resistant vaporizer device
USD887632S1 (en) 2017-09-14 2020-06-16 Pax Labs, Inc. Vaporizer cartridge
CN109171010A (zh) * 2018-09-10 2019-01-11 深圳市新宜康科技股份有限公司 液态尼古丁盐及其制备方法
GB201817861D0 (en) * 2018-11-01 2018-12-19 Nicoventures Trading Ltd Gel and crystalline powder
BR112021010614A2 (pt) * 2018-12-31 2021-08-24 Philip Morris Products S.A. Formulação de nicotina líquida compreendendo um solvente parcialmente solúvel em água
JP2022534009A (ja) * 2019-05-31 2022-07-27 ジェイティー インターナショナル エス．エイ． ニコチン液体製剤

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004076289A2 (en) * 2003-02-28 2004-09-10 Pfizer Health Ab A container comprising nicotine and the use and manufacture thereof
EP1618803A1 (en) * 2003-04-29 2006-01-25 Lik Hon A flameless electronic atomizing cigarette
US20060018840A1 (en) * 2004-06-28 2006-01-26 Nektar Therapeutics Aerosolizable formulation comprising nicotine
US20140345635A1 (en) * 2013-05-22 2014-11-27 Njoy, Inc. Compositions, devices, and methods for nicotine aerosol delivery

Family Cites Families (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1502132A (en) * 1975-05-27 1978-02-22 Ici Ltd Smoking materials
GB2133691B (en) * 1983-01-21 1986-05-21 Leo Ab Smoking substitutes for nasal administration
GB8301659D0 (en) * 1983-01-21 1983-02-23 Leo Ab Smoking substitutes
US4597961A (en) 1985-01-23 1986-07-01 Etscorn Frank T Transcutaneous application of nicotine
US4800903A (en) * 1985-05-24 1989-01-31 Ray Jon P Nicotine dispenser with polymeric reservoir of nicotine
DE3884246T2 (de) * 1987-02-10 1994-03-03 Reynolds Tobacco Co R Zigarette.
US5031646A (en) * 1990-01-16 1991-07-16 R. J. Reynolds Tobacco Company Cigarette
ATE246909T1 (de) 1994-03-07 2003-08-15 Theratech Inc Medikament enthaltende, adhesive, zusammenbaubare,transdermale abgabevorrichtung
SE9900215D0 (sv) * 1999-01-26 1999-01-26 Pharmacia & Upjohn Ab New use
US8256433B2 (en) 1999-07-16 2012-09-04 Aradigm Corporation Systems and methods for effecting cessation of tobacco use
CA2427283A1 (en) * 2000-11-03 2002-05-16 Recovery Pharmaceuticals, Inc. Device and method for the cessation of smoking
JP2003024036A (ja) * 2001-07-18 2003-01-28 Ikeda Denki Seisakusho:Kk 禁煙具
SE0201669D0 (sv) * 2002-06-03 2002-06-03 Pharmacia Ab New formulation and use thereof
US7767698B2 (en) * 2002-06-03 2010-08-03 Mcneil Ab Formulation and use thereof
US20040182403A1 (en) 2003-02-28 2004-09-23 Sven-Borje Andersson Container comprising nicotine and the use and manufacture thereof
CN2719043Y (zh) 2004-04-14 2005-08-24 韩力 雾化电子烟
CN101437497A (zh) * 2006-03-16 2009-05-20 尼科诺瓦姆股份公司 提供迅速释放尼古丁的口香糖组合物
US8657843B2 (en) 2006-05-03 2014-02-25 Applied Medical Resources Corporation Shield lockout for bladed obturator and trocars
CN201067079Y (zh) 2006-05-16 2008-06-04 韩力 仿真气溶胶吸入器
US7726320B2 (en) * 2006-10-18 2010-06-01 R. J. Reynolds Tobacco Company Tobacco-containing smoking article
US8991402B2 (en) * 2007-12-18 2015-03-31 Pax Labs, Inc. Aerosol devices and methods for inhaling a substance and uses thereof
CN102612361B (zh) * 2009-09-16 2014-11-05 菲利普莫里斯生产公司 传送药物的改良装置和方法
AT509046B1 (de) * 2010-03-10 2011-06-15 Helmut Dr Buchberger Flächiger verdampfer
SE535587C2 (sv) 2011-03-29 2012-10-02 Chill Of Sweden Ab Produkt innehållande ett fritt nikotinsalt och en ej vattenlöslig påse
US9351522B2 (en) 2011-09-29 2016-05-31 Robert Safari Cartomizer e-cigarette
US9854839B2 (en) 2012-01-31 2018-01-02 Altria Client Services Llc Electronic vaping device and method
US10004259B2 (en) 2012-06-28 2018-06-26 Rai Strategic Holdings, Inc. Reservoir and heater system for controllable delivery of multiple aerosolizable materials in an electronic smoking article
US20140261486A1 (en) * 2013-03-12 2014-09-18 R.J. Reynolds Tobacco Company Electronic smoking article having a vapor-enhancing apparatus and associated method
WO2014150245A1 (en) 2013-03-15 2014-09-25 Aradigm Corporation Methods for inhalation of smoke-free nicotine
US10799548B2 (en) 2013-03-15 2020-10-13 Altria Client Services Llc Modifying taste and sensory irritation of smokeless tobacco and non-tobacco products
GB2513637A (en) 2013-05-02 2014-11-05 Nicoventures Holdings Ltd Electronic cigarette
CN114223928A (zh) 2013-05-06 2022-03-25 尤尔实验室有限公司 用于气溶胶装置的烟碱盐调配物及其方法
US11013872B2 (en) 2013-12-19 2021-05-25 Philip Morris Products S.A. Aerosol-generating system for generating and controlling the quantity of nicotine salt particles
US9955726B2 (en) 2014-05-23 2018-05-01 Rai Strategic Holdings, Inc. Sealed cartridge for an aerosol delivery device and related assembly method
GB2535427A (en) 2014-11-07 2016-08-24 Nicoventures Holdings Ltd Solution
GB2532062A (en) 2014-11-07 2016-05-11 Nicoventures Holdings Ltd Container

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004076289A2 (en) * 2003-02-28 2004-09-10 Pfizer Health Ab A container comprising nicotine and the use and manufacture thereof
EP1618803A1 (en) * 2003-04-29 2006-01-25 Lik Hon A flameless electronic atomizing cigarette
US20060018840A1 (en) * 2004-06-28 2006-01-26 Nektar Therapeutics Aerosolizable formulation comprising nicotine
US20140345635A1 (en) * 2013-05-22 2014-11-27 Njoy, Inc. Compositions, devices, and methods for nicotine aerosol delivery

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11588287B2 (en) 2018-10-12 2023-02-21 Rai Strategic Holdings, Inc. Aerosol delivery device with improved connectivity, airflow, and aerosol paths
US11583003B2 (en) 2018-10-12 2023-02-21 Rai Strategic Holdings, Inc. Connectors for forming electrical and mechanical connections between interchangeable units in an aerosol delivery system
US11677201B2 (en) 2018-10-12 2023-06-13 Rai Strategic Holdings, Inc. Aerosol delivery device with improved connectivity, airflow, and aerosol paths
US11678700B2 (en) 2018-10-12 2023-06-20 Rai Strategic Holdings, Inc. Aerosol delivery device with visible indicator
US11856988B2 (en) 2018-10-12 2024-01-02 Rai Strategic Holdings, Inc. Connectors for forming electrical and mechanical connections between interchangeable units in an aerosol delivery system
US11967793B2 (en) 2018-10-12 2024-04-23 Rai Strategic Holdings, Inc. Aerosol delivery device with improved connectivity, airflow, and aerosol paths
US11974603B2 (en) 2018-10-12 2024-05-07 Rai Strategic Holdings, Inc. Aerosol delivery device with visible indicator
WO2021035103A1 (en) * 2019-02-15 2021-02-25 Bn Intellectual Properties, Inc. Nicotine formulation for active mesh nebulizer
WO2022180491A1 (en) * 2021-02-24 2022-09-01 Rai Strategic Holdings, Inc. Aerosol precursor formulations

Also Published As

Publication number Publication date
CN107072287A (zh) 2017-08-18
ES2832751T3 (es) 2021-06-11
MX2017005939A (es) 2017-07-19
EP3214957A1 (en) 2017-09-13
RU2695839C2 (ru) 2019-07-29
CA2964829C (en) 2024-04-02
BR112017009258A2 (pt) 2018-01-30
RU2019100397A3 (pl) 2019-05-22
PL3491941T3 (pl) 2021-06-14
KR20190058719A (ko) 2019-05-29
GB2532062A (en) 2016-05-11
RU2017115501A (ru) 2018-11-06
AR118187A2 (es) 2021-09-22
EP3738447A1 (en) 2020-11-18
CL2017001137A1 (es) 2018-01-05
KR101984834B1 (ko) 2019-05-31
GB201419866D0 (en) 2014-12-24
CN109965357B (zh) 2022-09-30
RU2017115501A3 (pl) 2018-11-06
PH12017500837A1 (en) 2017-10-30
ES2718222T3 (es) 2019-06-28
TR201904005T4 (tr) 2019-04-22
CA2964829A1 (en) 2016-05-12
AR102579A1 (es) 2017-03-08
AU2015341517A1 (en) 2017-05-04
AU2015341517B2 (en) 2018-01-18
MX2023011896A (es) 2023-10-18
EP3491941B1 (en) 2020-08-12
EP3491941A1 (en) 2019-06-05
CN107072287B (zh) 2019-02-26
CN109965357A (zh) 2019-07-05
EP3214957B1 (en) 2019-02-13
MY198202A (en) 2023-08-11
BR112017009258B1 (pt) 2022-05-03
WO2016071706A1 (en) 2016-05-12
HUE051844T2 (hu) 2021-03-29
PL3214957T3 (pl) 2019-07-31
JP6450002B2 (ja) 2019-01-09
PH12017500837B1 (en) 2017-10-30
KR102035196B1 (ko) 2019-10-22
KR20170066568A (ko) 2017-06-14
JP2017532968A (ja) 2017-11-09
HUE044286T2 (hu) 2019-10-28
RU2019100397A (ru) 2019-02-05
RU2677847C2 (ru) 2019-01-21

Similar Documents

Publication Publication Date Title
US20180228214A1 (en) Container containing a nicotine solution
US20210045428A1 (en) Solution comprising nicotine in unprotonated form and protonated form

Legal Events

Date Code Title Description
AS Assignment

Owner name: NICOVENTURES HOLDINGS LIMITED, UNITED KINGDOM

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:MCADAM, KEVIN GERARD;BRUTON, CONNOR;TRANI, MARINA;SIGNING DATES FROM 20170523 TO 20170524;REEL/FRAME:045875/0771

STPP Information on status: patent application and granting procedure in general

Free format text: FINAL REJECTION MAILED

STPP Information on status: patent application and granting procedure in general

Free format text: DOCKETED NEW CASE - READY FOR EXAMINATION

STPP Information on status: patent application and granting procedure in general

Free format text: NON FINAL ACTION MAILED

STPP Information on status: patent application and granting procedure in general

Free format text: RESPONSE TO NON-FINAL OFFICE ACTION ENTERED AND FORWARDED TO EXAMINER

STPP Information on status: patent application and granting procedure in general

Free format text: FINAL REJECTION MAILED

STPP Information on status: patent application and granting procedure in general

Free format text: DOCKETED NEW CASE - READY FOR EXAMINATION

STPP Information on status: patent application and granting procedure in general

Free format text: NON FINAL ACTION MAILED

AS Assignment

Owner name: NICOVENTURES TRADING LIMITED, UNITED KINGDOM

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:NICOVENTURES HOLDINGS LIMITED;REEL/FRAME:055424/0056

Effective date: 20200305

STPP Information on status: patent application and granting procedure in general

Free format text: RESPONSE TO NON-FINAL OFFICE ACTION ENTERED AND FORWARDED TO EXAMINER

STPP Information on status: patent application and granting procedure in general

Free format text: FINAL REJECTION MAILED

STPP Information on status: patent application and granting procedure in general

Free format text: DOCKETED NEW CASE - READY FOR EXAMINATION

STPP Information on status: patent application and granting procedure in general

Free format text: FINAL REJECTION MAILED

STPP Information on status: patent application and granting procedure in general

Free format text: DOCKETED NEW CASE - READY FOR EXAMINATION

STPP Information on status: patent application and granting procedure in general

Free format text: NON FINAL ACTION MAILED

STPP Information on status: patent application and granting procedure in general

Free format text: RESPONSE TO NON-FINAL OFFICE ACTION ENTERED AND FORWARDED TO EXAMINER

STPP Information on status: patent application and granting procedure in general

Free format text: FINAL REJECTION MAILED

STPP Information on status: patent application and granting procedure in general

Free format text: NON FINAL ACTION MAILED

STPP Information on status: patent application and granting procedure in general

Free format text: FINAL REJECTION MAILED

STCV Information on status: appeal procedure

Free format text: NOTICE OF APPEAL FILED

STCV Information on status: appeal procedure

Free format text: APPEAL BRIEF (OR SUPPLEMENTAL BRIEF) ENTERED AND FORWARDED TO EXAMINER

STCV Information on status: appeal procedure

Free format text: EXAMINER'S ANSWER TO APPEAL BRIEF MAILED