EP4011219A1 - Composition liquide pour inhalation pour cigarettes électroniques à cytotoxicité réduite - Google Patents

Composition liquide pour inhalation pour cigarettes électroniques à cytotoxicité réduite Download PDF

Info

Publication number
EP4011219A1
EP4011219A1 EP21210563.9A EP21210563A EP4011219A1 EP 4011219 A1 EP4011219 A1 EP 4011219A1 EP 21210563 A EP21210563 A EP 21210563A EP 4011219 A1 EP4011219 A1 EP 4011219A1
Authority
EP
European Patent Office
Prior art keywords
percentage
volume
equal
composition
optionally
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
EP21210563.9A
Other languages
German (de)
English (en)
Other versions
EP4011219C0 (fr
EP4011219B1 (fr
Inventor
Gianluca GIORGETTI
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.)
Vaporart Srl
Original Assignee
Vaporart Srl
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 Vaporart Srl filed Critical Vaporart Srl
Publication of EP4011219A1 publication Critical patent/EP4011219A1/fr
Application granted granted Critical
Publication of EP4011219C0 publication Critical patent/EP4011219C0/fr
Publication of EP4011219B1 publication Critical patent/EP4011219B1/fr
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • 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
    • A24B15/42—Treatment of tobacco products or tobacco substitutes by chemical substances by organic and inorganic substances

Definitions

  • the present invention relates to a liquid inhalation composition for electronic cigarettes with reduced cytotoxicity.
  • the heated-tobacco inhalation systems are those which are most similar to traditional smoking for smokers, both in terms of the flavoring of the tobacco and of consumption methods and times, similar to those of a cigarette.
  • some toxic substances contained in tobacco are formed even before the combustion thereof, such as, in addition to nicotine, nitrosamines. These substances are therefore not eliminated by reducing the combustion temperature to no more than 350°C.
  • compositions for electronic cigarettes do not contain such toxic or carcinogenic substances, apart from a controlled amount of nicotine, which is essential to make the inhalation of the composition pleasant by the traditional smoker. Furthermore, the possibility of flavoring the composition in various manners forms a further attraction.
  • the base composition which consists for the most part of a mixture of propylene glycol and glycerol in a volume ratio of 50:50, or for a denser vapor of 30:70, has an inherent toxicity, albeit much more reduced than that of a traditional cigarette and the heated-tobacco system described above.
  • the present invention relates to a composition for inhalation by means of an electronic cigarette comprising:
  • the invention also relates to a base composition
  • a base composition comprising:
  • the invention still further relates to a kit comprising:
  • the present invention is directed to a composition for inhalation by means of electronic cigarettes comprising:
  • the glycerol/propylene glycol mixture is at a volume ratio between 50:50 and 70:30.
  • the percentage by volume of the glycerol/propylene glycol mixture will not be greater than 90%.
  • the glycerol is preferably vegetable glycerol.
  • the percentage of nicotine optionally present in the composition should not be greater than the amount allowed by current legislation, in particular it should be less than or equal to 20 mg/ml.
  • the water is preferably demineralized water.
  • the flavorings can be of any type normally used for electronic cigarettes, such as fruit flavorings, tobacco flavorings, mentholates or mixtures thereof.
  • the flavorings can be added to a base composition which does not contain them directly by the smoker. In this case, glycol-based flavorings are available to add to the composition as desired.
  • the invention further relates to a base composition
  • a base composition comprising
  • the pH adjuster is preferably an organic or inorganic acid, more preferably selected from orthophosphoric acid, lactic acid and citric acid.
  • the weight percentage of the pH adjuster in the composition depends on both the nature of the pH adjuster and the percentage of the various components used in the composition. For example, in a composition containing about 90% by volume of 50:50 glycerol/propylene glycol mixture, about 5% water, about 10% flavorings (apple/kiwi), nicotine 8 mg/ml, orthophosphoric acid in a weight percentage of 0.1% adjusted the pH of the composition to 7.5.
  • the pH is preferably between 7.2 and 7.6, more preferably between 7.3 and 7.6 or between 7.4 and 7.6 or is of about 7.5.
  • the invention still further relates to a kit comprising:
  • the present invention originates from the evidence that the known compositions for electronic cigarettes have a basic pH.
  • the present Applicant has conducted experiments and has verified that such a basic pH is responsible for a certain cytotoxicity towards lung cells (human lung fibroblasts).
  • the Applicant has also discovered that by lowering the pH of the composition to a pH between 7 and 7.6, such toxicity is substantially reduced if not eliminated.
  • cytotoxicity of a composition according to the invention towards compositions of the prior art was evaluated through the MTT test: cell survival test with human fibroblasts of pulmonary origin grown in monolayer for the evaluation of the biocompatibility of smoke with mucous membranes.
  • the test aims at evaluating the cytotoxicity of the smoke condensate obtained with electronic cigarettes with pH correction to neutrality according to the invention on a cell culture of human lung fibroblasts, as described in the UNI EN ISO 10993-5 and ISO 4387:2019 standards related to the biological evaluation of medical devices, appropriately modified for the purpose.
  • the cytotoxicity of the condensate obtained by simulating the exposure to which the user of the electronic cigarette is subjected is an indicator of the safe use of the device in hand and the overall toxicity thereof towards the respiratory epithelium.
  • the method used is that of MTT, which is simple and reproducible, originally developed by Mossman.
  • An increase or decrease in viable cells results in a concomitant change in absorbance which can be regarded as an indicator of the degree of cytotoxicity caused by exposure to the test substances.
  • the cells are also examined under a microscope after contact with the sample to evaluate any changes in the morphology thereof, membrane integrity or any lysis phenomena.
  • HPF Human Lung Fibroblasts
  • Cigarette smoke is sampled using a smoke machine consisting of a vacuum system and a 100 ml flask connected to an electronic cigarette.
  • the electronic cigarette is positioned vertically on an inert plastic fitting. The positioning allows the metal resistance inside the tank and used to heat the liquid to always remain in contact with the liquid itself, as indicated by the manufacturer.
  • the electronic cigarette loaded with the appropriate liquid was left to rest about 20 minutes before aspiration, so that the cotton inside the tank was correctly moistened with liquid, after which the first 2/3 puffs were discarded.
  • the flask is connected by silicone tubes to a flow meter inside the instrument, which is in turn connected to a vacuum pump and to a PC with control software.
  • the presence of a flow meter allows the constant setting of the aspiration flow.
  • 30 ml of sterile medium were used for the preparation of the condensates.
  • An aspiration/inhalation simulation is performed with a duration of 3" with a pause lasting 45" between one aspiration and the other, to facilitate the collection of the condensate in the medium, keeping the flask constantly under stirring during the experiment, in accordance with ISO 4387:2019.
  • the aspiration flow is regulated at 1 L/min. 150 aspiration/inhalation cycles are performed, equal to 25 traditional cigarettes.
  • the smoke from the electronic cigarette, loaded with the special liquid at the beginning of the session, is continuously sampled for the expected number of cycles.
  • the medium with the condensate obtained from such an experiment was brought to pH 7.5 with lactic acid and subjected to cytotoxicity tests.
  • Human lung cells were seeded in 96-well plates and allowed to grow for 24h at 37°C and 5% CO 2 . On the second day, the medium was removed and replaced by the freshly prepared condensate from the cigarette to be tested.
  • the tested concentrations are the condensate as is and the subsequent serial 1:2 dilutions thereof in medium.
  • the cytotoxicity test (MTT) was then performed to evaluate the cell survival percentage.
  • the culture medium is aspirated and the cells incubated in 100 ⁇ l/well of a 1 mg/ml solution of MTT, for 2 hours at 37°C.
  • the solution is removed and replaced by 200 ⁇ l/well of DMSO with subsequent 30' of incubation at room temperature and stirring at medium speed.
  • the absorbance at 570 nm is read with a colorimeter (Tecan INFINITE F200) provided with a plate reader by subtracting the background reading at 650 nm.
  • % of cell viability OD 570 nm ⁇ 650 nm product tested / OD 570 nm ⁇ 650 nm white ⁇ 100 .
  • IC 50 Inhibiting Concentration 50
  • Conc > 50 first concentration which gave a cell viability above 50%
  • Conc ⁇ 50 first concentration which gave a cell viability less than 50%
  • a reduction in cell viability > 30% is considered a cytotoxic effect.
  • Figure 1 shows the graph of cell viability vs concentration for the positive control (SLS).
  • Figure 2 shows the graph of cell viability vs concentration for the composition of the invention at pH 7.5.
  • Figure 3 shows the graph of cell viability vs concentration for the electronic cigarette composition of the prior art (pH 8.9).
  • Figure 4 shows the graph of cell viability vs concentration for the HEETS Turquoise selection heated-tobacco cigarette.
  • composition for electronic cigarettes according to the invention is much less cytotoxic than both the composition of the prior art without acidity adjuster and, to an even greater extent, the heated-tobacco cigarette.
  • the invention further relates to a pH adjuster acid for use in preventing pulmonary cytotoxicity in subjects intaking vapors by means of electronic cigarettes, in which said pH adjuster acid is added to an electronic cigarette composition comprising a glycerol/propylene glycol mixture in a percentage by volume between 80% and 99%, optionally water in a percentage by volume less than or equal to 6%, preferably less than or equal to 5%, optionally nicotine in a percentage by weight/volume not exceeding 0.2%, optionally flavorings in a percentage by volume less than or equal to 15%, preferably less than or equal to 10%, and in which said pH adjuster acid gives said composition a pH between 7.0 and 7.6.
  • Said pH adjuster acid is preferably selected from orthophosphoric acid, lactic acid and citric acid and the composition for electronic cigarettes is preferably as defined above.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Toxicology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
EP21210563.9A 2020-12-09 2021-11-25 Composition liquide pour inhalation pour cigarettes électroniques à cytotoxicité réduite Active EP4011219B1 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
IT102020000030173A IT202000030173A1 (it) 2020-12-09 2020-12-09 Composizione liquida da inalazione per sigarette elettroniche a citotossicità ridotta

Publications (3)

Publication Number Publication Date
EP4011219A1 true EP4011219A1 (fr) 2022-06-15
EP4011219C0 EP4011219C0 (fr) 2025-05-07
EP4011219B1 EP4011219B1 (fr) 2025-05-07

Family

ID=74669409

Family Applications (1)

Application Number Title Priority Date Filing Date
EP21210563.9A Active EP4011219B1 (fr) 2020-12-09 2021-11-25 Composition liquide pour inhalation pour cigarettes électroniques à cytotoxicité réduite

Country Status (2)

Country Link
EP (1) EP4011219B1 (fr)
IT (1) IT202000030173A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118266629A (zh) * 2023-07-13 2024-07-02 比亚迪精密制造有限公司 猕猴桃味香精和电子烟烟油及其制备方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130255702A1 (en) * 2012-03-28 2013-10-03 R.J. Reynolds Tobacco Company Smoking article incorporating a conductive substrate
US20140096781A1 (en) * 2012-10-08 2014-04-10 R. J. Reynolds Tobacco Company Electronic smoking article and associated method
WO2014190079A2 (fr) * 2013-05-22 2014-11-27 Njoy, Inc. Compositions, dispositifs, et procédés pour administration d'aérosols de nicotine
CN110558605A (zh) * 2019-09-27 2019-12-13 深圳雾芯科技有限公司 电子烟液
WO2020239907A1 (fr) * 2019-05-31 2020-12-03 Jt International S.A. Formulation liquide de nicotine

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130255702A1 (en) * 2012-03-28 2013-10-03 R.J. Reynolds Tobacco Company Smoking article incorporating a conductive substrate
US20140096781A1 (en) * 2012-10-08 2014-04-10 R. J. Reynolds Tobacco Company Electronic smoking article and associated method
WO2014190079A2 (fr) * 2013-05-22 2014-11-27 Njoy, Inc. Compositions, dispositifs, et procédés pour administration d'aérosols de nicotine
WO2020239907A1 (fr) * 2019-05-31 2020-12-03 Jt International S.A. Formulation liquide de nicotine
CN110558605A (zh) * 2019-09-27 2019-12-13 深圳雾芯科技有限公司 电子烟液

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118266629A (zh) * 2023-07-13 2024-07-02 比亚迪精密制造有限公司 猕猴桃味香精和电子烟烟油及其制备方法

Also Published As

Publication number Publication date
EP4011219C0 (fr) 2025-05-07
IT202000030173A1 (it) 2022-06-09
EP4011219B1 (fr) 2025-05-07

Similar Documents

Publication Publication Date Title
JP6030255B2 (ja) 電子喫煙装置のためのタバコ抽出物を調製する方法
Tangerman et al. Extra-oral halitosis: an overview
Armitage et al. The effect of inhalation volume and breath-hold duration on the retention of nicotine and solanesol in the human respiratory tract and on subsequent plasma nicotine concentrations during cigarette smoking
RU2745735C1 (ru) Продукт
FI83019C (fi) Foerfarande foer tillsaettande av aromaemnen i tobak.
Dalhamn et al. Mouth absorption of various compounds in cigarette smoke
Wheeler et al. Does the burning of moxa (Artemisia vulgaris) in traditional Chinese medicine constitute a health hazard?
JP2005503819A (ja) タバコ主流煙からｐ−ベンゾセミキノンを減少させる活性炭フィルタ
EP4011219A1 (fr) Composition liquide pour inhalation pour cigarettes électroniques à cytotoxicité réduite
Bozhilova et al. Optimization of aqueous aerosol extract (AqE) generation from e-cigarettes and tobacco heating products for in vitro cytotoxicity testing
Watson et al. Determination of tar, nicotine, and carbon monoxide yields in the smoke of bidi cigarettes
BR0309909B1 (pt) Processo de redução de teor de TSNA em folha de tabaco
CN106556691B (zh) 一种检测电子烟制品对细胞过氧化氢酶酶活力影响的方法
Fukano et al. Heme oxygenase-1 gene expression in human alveolar epithelial cells (A549) following exposure to whole cigarette smoke on a direct in vitro exposure system
Lee et al. Comparative genotoxicity testing of mainstream whole smoke from cigarettes which burn or heat tobacco
JPH0662824A (ja) タバコ煙からのフリ−ラジカルの除去法
Popa et al. CO2 laser-photoacoustic study of exhaled breath produced by electronic vs. traditional cigarettes
CN101238911B (zh) 一种卷烟成品后处理方法
US12239957B2 (en) Flow-through aerosol capture device
Moldoveanu et al. Determination of hydroxybenzenes in exhaled cigarette smoke
CN107807233A (zh) 检测电子烟气溶胶水提物对细胞超氧化物歧化酶活性影响的方法
CN117156984A (zh) 用于供电子烟吸入的液体组合物
Alkalidy The effect of using electronic cigarettes on the blood gases in the blood of people addicted to smoking electronic cigarettes.
United States. Public Health Service. Office of the Surgeon General How tobacco smoke causes disease: the biology and behavioral basis for smoking-attributable disease: a report of the Surgeon General
CN102221597A (zh) 一种卷烟风格特征一致性感官检验方法

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN PUBLISHED

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20221012

RBV Designated contracting states (corrected)

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: EXAMINATION IS IN PROGRESS

17Q First examination report despatched

Effective date: 20240419

REG Reference to a national code

Ref country code: DE

Ref legal event code: R079

Ref document number: 602021030343

Country of ref document: DE

Free format text: PREVIOUS MAIN CLASS: A24B0015167000

Ipc: A24B0015420000

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: GRANT OF PATENT IS INTENDED

INTG Intention to grant announced

Effective date: 20240705

RIC1 Information provided on ipc code assigned before grant

Ipc: A24B 15/167 20200101ALI20240628BHEP

Ipc: A24B 15/42 20060101AFI20240628BHEP

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE PATENT HAS BEEN GRANTED

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 602021030343

Country of ref document: DE

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

U01 Request for unitary effect filed

Effective date: 20250604

U07 Unitary effect registered

Designated state(s): AT BE BG DE DK EE FI FR IT LT LU LV MT NL PT RO SE SI

Effective date: 20250612

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: ES

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20250507

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20250808

Ref country code: NO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20250807

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: PL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20250507

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: HR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20250507

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: RS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20250807

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20250907

U20 Renewal fee for the european patent with unitary effect paid

Year of fee payment: 5

Effective date: 20251020

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SM

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20250507

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20250507

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20250507

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

REG Reference to a national code

Ref country code: CH

Ref legal event code: L10

Free format text: ST27 STATUS EVENT CODE: U-0-0-L10-L00 (AS PROVIDED BY THE NATIONAL OFFICE)

Effective date: 20260318

26N No opposition filed

Effective date: 20260210