WO2015101760A1 - Use of a composition containing 1,3-propanediol as an e-liquid - Google Patents

Abstract

The invention relates to the use of a composition containing 1, 3-propanediol as an electronic cigarette liquid. The invention also relates to a liquid composition for electronic cigarettes comprising 1, 3-propanediol, as well as at least one compound selected from nicotine, a nicotine substitute and an aroma. The invention also relates to an electronic cigarette containing said composition.

Description

 Use of a composition containing

 1,3-propanediol as e-liquid

TECHNICAL AREA

 The present invention relates to the use of a composition containing 1,3-propanediol as an electronic cigarette liquid. It also relates to an electronic cigarette liquid composition comprising 1,3-propanediol, as well as nicotine and / or at least one flavor, and an electronic cigarette containing this composition.

 BACKGROUND OF THE INVENTION

 The e-cigarette market is currently developing significantly as it allows the consumer to maintain the ritual associated with the use of cigarettes without suffering the deleterious effects of the harmful substances it contains.

 The electronic cigarette or e-cigarette runs on electricity without burning. It produces a mist of fine particles, commonly called vapor or artificial smoke, visually resembling the smoke produced by burning tobacco. This vapor can be flavored (aroma of tobacco, mint, fruit, chocolate, etc.) and contain or not nicotine. In properly manufactured and used e-cigarettes, the aerosol contains, according to the available data, far fewer deleterious substances to health than tobacco smoke, in particular no solid particles, tar, other carcinogens, or monoxide. of carbon (CO).

 The e-cigarette has three main parts contained in a plastic or metallic envelope:

- a battery, a cartridge or reservoir containing a liquid called "e-liquid", and

 - an atomizer.

 The battery is most of the time the largest part of the e-cigarette on the disposables. Reusable cigarettes are "low voltage" batteries (accumulators), rechargeable by USB cable or charger. In reusable e-cigarettes, the tube housing the battery is screwed onto the cartridge containing the liquid. On some models, an indicator light usually a red or blue diode - is placed at the other end of the battery tube.

 The e-liquid storage device may take the form of a cartridge (generally made of silicone, PMMA or stainless metal) or a tank (in particular PMMA / polyethylene, borosilicate glass or stainless metal) optionally supplemented with a device for collecting the liquid by capillarity (in particular silica, fiberglass, ceramic metal fabric, nylon thread or borosilicate fiber) in contact with the vaporization system. The atomizer makes it possible to convert the e-liquid into fog simulating smoke. It consists of a spiral or wire mesh that forms a heating resistor. It is more and more often integrated in the refillable cartridge. A micro-valve sensitive to depression caused by inspiration or a manually triggered contactor allows the battery to feed the atomizer. The e-cigarette can be single-use or reusable.

 The e-liquids used are mainly composed of the following constituents:

 - synthetic propylene glycol (approximately 65%)

 - glycerol (about 25%)

- water (5 to 10%) - aromas and colors (2 to 5%)

 - nicotine (0 to 20 mg / ml)

 Some e-liquids may also contain significant amounts of ethanol (> 1%).

 Some products may be free of synthetic propylene glycol. The objective is in this case to be able to claim products of exclusively vegetable origin. This objective is achieved, however, to the detriment of the longevity of heating resistors, which clog very quickly. In addition, the quality of the emitted smoke is far from adequate in terms of vapor density, and the organoleptic properties of the liquids are strongly modified, since the release of the flavors in the absence of propylene glycol is made less immediate. Moreover, the exclusive use of glycerol forces to load the product with water, in order to reduce the viscosity of the e-liquid and thus facilitate the filling of the e-cigarette. But, again, the impact of a high water content radically changes the quality of the vapor emitted and leads to excessive corrosion of the materials as well as rapid and excessive consumption of the e-liquid (faster vaporization). Finally, another problem related to the exclusive use of glycerol lies in the fact that this compound is significantly less vaporizable than propylene glycol, so that its vaporization requires a significantly higher heating temperature, which can lead to its degradation and the formation of unwanted by-products such as acrolein.

Therefore, the use of synthetic propylene glycol in a larger quantity than glycerol is most often preferred, which does not allow manufacturers to claim a natural origin of their products. In addition, propylene glycol is obtained according to one of the most energy-consuming processes in the world. petrochemical and de facto has a strong environmental footprint (Eissen & al, Angew Chem Int, Ed., 2002, 41, 414-436) which results in high energy consumption and high production of volatile organic compounds (VOCs). ) and waste. In addition, the synthetic propylene glycol is obtained from propylene oxide according to a continuous hydration process, according to the following scheme: + poigïycois

 The production of propylene glycol is accompanied by the formation of secondary products (di-, and tri- and tetrapropylene glycols) and unconverted propylene oxide (Petrochemical Processes: Major Oxygenated, Chlorinated and Nitrated Derivatives - Alain Chauvel, Gilles Lefebvre - TECHNIP Editions - p26), horn illustrated below:

HC CH ₂ + .CH CH * ^■ .CH C .CH

 / \ / y \ y \

H ₃ C HO ^' CH ₂ HO CH ₂ CH ₂ OH

 Pi¾ & ytetie Prcpyiene Diprapytene

 Oxide Gt coi G! Yoot

Therefore, after purification, the minor and recurrent organic impurities of propylene glycol are di- and tripropylene glycol, as well as propylene oxide whose residual content according to the producers is of the order of 5 to 10 ppm ( Propylene Glycol - CIR Expert Panel, June 28-29, 2010 - Draft Report). However, propylene oxide is classified by North American and European environmental agencies as a carcinogenic compound and mutagenic in animals and as a probable carcinogen in humans. Therefore, it is important to limit exposure to this compound. Also, the Report and Expert Opinion on the e-Cigarette published by the French Office for Tobacco Prevention (OFT) in May 2013 stresses the need to ensure the absence of carcinogenic contaminants in e-liquids. In fact, it is necessary to avoid the presence of a toxic compound such as propylene oxide and, to a lesser extent, the presence of organic impurities belonging to the family that is strongly criticized from the toxicological point of view of glycol ethers, which alter the quality of e-liquids, like di- and tripropylene glycols.

 A solution to the aforementioned problems has been proposed in the application WO 2013/088230. It consists of substituting propylene glycol of plant origin for synthetic propylene glycol, obtained by catalytic hydrogenation of sorbitol, itself derived from corn. Propylene glycol is combined with glycerol of plant origin, nicotine that can be extracted from tobacco leaves and possibly with aromas of natural origin, to obtain an e-liquid of entirely vegetable origin.

While this solution effectively overcomes the disadvantages associated with the use of synthetic propylene glycol, it has now been demonstrated that the vapor density and the aromatic power produced by these e-liquids of vegetable origin could be improved by replacing propylene glycol with 1,3-propanediol (PDO) and that this effect was particularly pronounced in the absence of glycerin or in a low glycerine e-liquid composition. By eliminating glycerol, the use of PDO also contributes to protecting the heating device of electronic cigarettes by suppressing the phenomenon rapid fouling observed in the presence of glycerine. Another advantage related to the absence of glycerine is that the steam produced is freed from toxic and carcinogenic impurities resulting from the thermal decomposition of glycerol.

It has furthermore been observed that PDO makes it possible to obtain e-liquids devoid of nicotine recreating the tingle throat (or "throat hit") typically experienced by the user of a conventional cigarette, during the passage of the nicotine in the mouth. Until now, this effect, much sought after by e-liquid users, was achieved only by adding a few drops of a product based on propylene glycol, glycerin and flavors to the e-liquid (E-Liquid Flash ^® by FLAVOR ART). However, the latter has all the disadvantages mentioned above, related to the use of propylene glycol and glycerine.

 PDO of plant origin is today produced industrially by fermentation of glucose. It is currently used as an intermediate resin synthesis, as a solvent, humectant, preservative in the food industry, cosmetics, pharmaceuticals and personal care products, and as a component of hydraulic fluids, antifreezes, brake fluids, coolants, as a component of cleaning liquids, detergents, co-solvent paints, and solvents in the printing ink industry. Also, to the knowledge of the Applicant, the PDO has never been described as constituting e-liquids.

 SUMMARY OF THE INVENTION

The present invention thus relates to the use of a composition containing 1,3-propanediol and at least one additive selected from the group consisting of glycerine, nicotine, a substitute of nicotine and aroma as an electronic cigarette liquid.

 It also relates to an electronic cigarette liquid composition comprising 1,3-propanediol, as well as at least one compound selected from nicotine, a nicotine substitute and a flavor.

 It also relates to an electronic cigarette containing this composition.

 It also relates to the use of 1,3-propanediol in an electronic cigarette liquid containing or not nicotine, to improve the tingling of the groove felt by a user of said liquid and / or the ease of aspiration of the vapor produced by said liquid and use of 1,3-propanediol in an electronic cigarette liquid containing nicotine, to improve the bioavailability of nicotine.

 It also relates to a use of 1,3-propanediol, optionally in the presence of glycerin, in an electronic cigarette liquid to enhance the aromatic power and a use of 1,3-propanediol, optionally in the presence of glycerin, in a liquid of electronic cigarette to limit or to suppress the formation of thermolysis co-products.

 Finally, it relates to the use of 1,3-propanediol, optionally in the presence of glycerin, in an electronic cigarette liquid containing nicotine, to deliver nicotine steadily.

 DETAILED DESCRIPTION OF EMBODIMENTS

In the present application, the term "electronic cigarette" means all devices equipped with electrical means producing steam and delivering nicotine and / or aroma. This definition therefore includes, in particular, personal vaporizers (VPs), nicotine delivery systems (ENDS for "Electronic Nicotine Delivery System", or ENDD for "Electronic Nicotine Delivery Device"), as well as electronic cigars, electronic pipes and electronic shisha, tobacco-based cigarettes that are heated or contain a flavor of tobacco obtained by maceration.

 By "plant-based" compound is meant a compound comprising at least 95% biobased carbon, as determined by ASTM standard D6866-12 (Standard Test Methods for Determining the Biobase Content of Solid, Liquid, and Gaseous Samples Using Radiocarhon Analysis).

 As indicated above, the invention relates to the use of a composition containing PDO as an electronic cigarette liquid (hereinafter, "e-liquid"). The PDO can be synthetic or, according to a preferred embodiment of the invention, it can be obtained from vegetable raw materials and referred to herein as "PDO of plant origin".

 According to one embodiment, the PDO of plant origin is obtained by fermentation.

The PDO of plant origin can be obtained by fermentation of glucose, in the presence of a native bacterium or genetically modified, selected in particular from strains of Klebsiella (including pneumoniae), Clostridium (including butyricum), Citrobacter (including freundii), Serratia and Escherichia coli, preferably Escherichia coli, and more preferably Escherichia coli K-12. An example of a genetically modified strain is described in US application 2012/258521. The bio-based glucose used to produce PDO is usually derived from sugar or starchy plants such as sugar cane, maize, wheat, potato, sugar beet, rice, or sorghum. Preferably, the glucose is derived from non-genetically modified plant varieties, such as sugar cane or beet. Better still, glucose is derived from non-food lignocellulosic biomasses such as wood, straw, palm bunchees, bagasse, and non-genetically modified maize stalks. The product of the fermentation can be recovered, and the PDO purified, by membrane filtration, electrodialysis, concentration or rectification, for example, or by a combination of these techniques. The PDO can in particular be purified by distillation, an operation which makes it possible to reach a purity of 99.8%. The impurities present at 0.2% are water and propanol-1 (Chatterjee et al., Glycerol to Propylene Glycol / Department of Chemical & Biomolecular Engineering Senior Design Reports (CEE), University of Pennsylvania - April 12, 2011 ), a compound devoid of toxicity. The PDO may represent from 50 to 99% by weight, preferably from 60 to 95% by weight, more preferably from 70 to 90% by weight, relative to the total weight of the composition.

 The composition used according to the invention may also contain propylene glycol. The latter may be of synthetic or vegetable origin (that is to say obtained from vegetable raw materials). In the latter case, which is preferred, the propylene glycol may in particular be obtained by hydrogenolysis of sorbitol or vegetable glycerol (New and Future Developments in Catalysis: Catalytic Biomass Chemistry - S. Suib Editor / Elsevier - 2013, pp 13-17 or by hydrogenation of vegetable lactic acid (J. Van Haveren & others Bulk Chemicals from Biomass, BioFPR, november 1, 2007. pp 41-57).

The biosourced glycerol used to produce propylene glycol may be of animal or plant origin, preferably plant-based. Vegetable glycerol is derived from the hydrolysis (acidic or basic) of vegetable oils or their alcoholysis (transesterification). These oils belong in a non-limiting manner to the group of oils of soya, palm, palm kernel, copra, rapeseed, sunflower, corn germ, cotton, olive, sesame, rice bran, flax, castor oil, avocado, peanut, safflower, grapeseed, or tall oil. It is preferred to use glycerol from non-genetically modified plant varieties, such as palm, rapeseed, sunflower, or copra oils.

 The sorbitol or biosourced lactic acid used to produce propylene glycol of plant origin is generally derived from sugar or starchy plants such as sugar cane, corn, wheat, potato, sugar beet, rice, or sorghum. Preferably, sorbitol or lactic acid from non-genetically modified plant varieties such as sugar cane or beet is used. Better yet, sorbitol or lactic acid is obtained from non-food lignocellulosic biomasses such as wood, straw, palm bunchees, bagasse, and non-genetically modified maize stalks.

 It should be noted that the aforementioned methods make it possible to obtain not only propylene glycol, but also PDO as a co-product, the proportions of which can be adjusted by appropriately selecting the reaction conditions (Nur Dyana bt Saar - Dissertation submitted in Partial fulfillment of the requirements for the Bachelor of Engineering (Hons) Chemical Engineering, Universiti Teknologi PETRONAS, May 2013).

The propylene glycol may represent from 2 to 50% by weight, preferably from 10 to 40% by weight, more preferably from 20 to 30% by weight, relative to the total weight of the composition. According to the invention, it is preferred that the composition used as e-liquid contains no or little glycerin, that is to say it contains from 0 to 40% by weight of glycerol, preferably from 0 to 20% by weight. by weight, for example from 0 to 5% by weight of glycerin or from 5 to 20% by weight of glycerin. It has indeed been observed, as indicated above, that the absence of glycerine makes it possible to avoid the formation of undesirable by-products when heating the glycerine. It has been found that at the temperature reached by the resistance of an electronic cigarette, glycerol decomposes to acrolein (Cordoba et al Proceedings of COBEM 2011 - 21st Brazilian Congress of Mechanical Engineering, 24-28 October 2011, Natal RN, Brazil Metzger Brian; Glycerol Combustion - thesis 1 University of North Carolina, ¹ August 2007), a highly toxic compound at very low concentration (Goniewicz et al Levels of Selected Carcinogens and Toxicants in Vapor from Electronic Cigarettes -. TC Online First, published on March 6, 2013 under 10.1136 / tobaccocontrol- 2012-050859). Surprisingly, it was also noted that the absence of glycerine significantly increased the vapor density and aromatic power of the electronic cigarette. Advantageously, when it is present, the glycerin is of vegetable origin and obtained according to the methods described above.

 Apart from the abovementioned constituents, the composition used according to the invention may additionally contain at least one compound chosen from nicotine, a nicotine substitute (typically a non-addictive molecule but with a sensory effect close to that of nicotine) and an aroma.

Nicotine can be of synthetic or plant origin and should preferably meet the criteria of purity described in the US Pharmacopoeia (USP) and European (PE) in force. It can in particular be extracted from tobacco leaves or obtained by chemical synthesis. The nicotine concentration in the composition according to the invention may range from 0 to 50 mg / ml, preferably from 2 to 20 mg / ml.

 According to one embodiment, the composition used according to the invention has an aroma content of less than 10% by weight.

Flavorings may also be flavor of plant or synthetic origin such as those registered in the food and / or pharmaceutical, especially those listed in Regulation EU No 872/2012 of ¹ October 2012 and in the US Pharmacopoeia ( USP) and European (PE) in force. The concentration of flavors can range from 0 to 30% by weight, preferably from 1 to 8% by weight, more preferably from 2 to 5% by weight, relative to the total weight of the composition.

 The composition used according to the invention may also comprise water and / or an alcohol such as ethanol and / or at least one dye. The water and the alcohol may each represent from 0 to 20% by weight, preferably from 1 to 10% by weight, relative to the total weight of the composition. The dyes may be dyes of vegetable or synthetic origin, such as those approved in the food and / or pharmaceutical fields and in particular those listed in the EU Regulation No. 1331/2008 and in the US and European Pharmacopoeias (USP) ( PE) in force. The concentration of flavors can range from 0 to 30% by weight, preferably from 1 to 8% by weight, more preferably from 2 to 5% by weight, relative to the total weight of the composition.

However, it is preferred according to the invention that the composition does not comprise ethanol and / or does not comprise no water, except that possibly contained in the raw materials that the composition contains. Indeed, water can promote the development of pathogenic microorganisms of microbial origin and its use generally requires the use of preservatives or the production of a sterilizing microfiltration. In addition, the addition of water to e-liquids induces a transformation of nicotine base into protonated nicotine. However, it is known to those skilled in the art that the protonated form of nicotine is significantly less ^bio¬¬ assimilable, and in fact less addictive, than nicotine base. Thus, 1,3-propanediol makes it possible to formulate very fluid e-liquids without having to add osmosis water, in which the nicotine is present in base form and in its highly bioavailable form, which clearly improves the control. delivery of nicotine, especially during smoking cessation.

 Advantageously, the composition according to the invention has a kinematic viscosity at 20 ° C. of less than 200 mPas / s, preferably less than 100 mPa.s, more preferably less than 75 mPa.s, better still less than 60 mPa.s. said viscosity being greater than 30 mPa.s, preferably greater than 40 mPa.s and more preferably greater than 50 mPa. s.

 The invention also relates to an electronic cigarette containing the composition as described above. This is generally arranged in a cartridge secured to a receptacle housing a power supply system connected to a device for atomizing the composition.

It still relates to the use of 1,3-propanediol in an electronic cigarette liquid containing or not nicotine, to improve the tingling of the throat felt by a user of said liquid and / or the ease of suction of the vapor produced by said liquid.

 It also relates to the use of 1,3-propanediol, optionally in the presence of glycerine, in an electronic cigarette liquid to enhance the aromatic power.

 It also relates to the use of 1,3-propanediol, optionally in the presence of glycerin, in an electronic cigarette liquid to limit or to suppress the formation of thermolysis coproducts.

 It also relates to the use of 1,3-propanediol in an electronic cigarette liquid containing nicotine, to improve the bioavailability of nicotine.

 Finally, it relates to the use of 1,3-propanediol, optionally in the presence of glycerin, in an electronic cigarette liquid containing nicotine, to deliver nicotine steadily.

 The invention will be better understood in the light of the following examples, which are given for purely illustrative purposes and are not intended to limit the scope of the invention, defined by the appended claims.

 EXAMPLES

 Example 1 (Comparative) Preparation and Analysis of a Composition Based on Propylene Glycol of Plant Origin

In a glass mixer equipped with a mechanical stirring precisely mixing 10.00 kg of propylene glycol vegetable (rapeseed) marketed by the company under the Oléon Radianol Reference ^® 4710, USP Pharmacopoeia grade), 1.00 kg of vegetable glycerin (marketed by the company Oléon under the reference Glycerin 4810, Pharmacopoeia USP and PE grade), 450.0 g of fruity apple flavor (marketed by Safisis under the reference PT 128) and 114.50 nicotine plant (marketed by Nicobrand under the reference Nicotine Free Base, Pharmaceutical grade Nicotine> 99%). Stirring of the mixture (50 rpm) is maintained for 20 minutes. A 500g sample is taken for analysis.

 The mixture is analyzed by gas chromatography coupled to mass spectrometry according to the method described in the publication by Cao et al. (Cao XL, Corriveau J. An isotope dilution headspace method with gas chromatography-mass spectrometry for determination of propylene oxide in Food Addit Contam Part A Chem Anal Control Expo Risk Assessment 2009 Apr; 26 (4): 482-6.

 At the same time, an analysis is done to determine the biosourced carbon content according to ASTM D6866-12.

 Results:

 Under the conditions of analysis (sensitivity 0.5 ng / g), no trace of propylene oxide or di- and tripropylene glycols is detected.

 The biobased carbon content of the mixture is equal to

99.8%.

 Example 2 Preparation and Analysis of a Composition Based on PDO

The procedure is identical to Example 1, but replacing propylene glycol vegetable by the 1, 3-propanediol provided by DuPont Tate & Lyle & LLC under reference Zemea ^® propanediol.

 Results:

 Under the conditions of analysis (sensitivity 0.5 ng / g), no trace of propylene oxide or di- and tripropylene glycols is detected.

 The biobased carbon content of the mixture is equal to

99.7%. Example 3 (Comparative) Preparation and Analysis of a Composition Based on Synthetic Propylene Glycol

The procedure is identical to Example 1, but substituting propylene glycol plant with synthetic propylene glycol supplied by Dow under the reference Dow ^® Propylene glycol, USP grade.

 Results:

 Under the conditions of analysis (sensitivity 0.5 ng / g), no trace of di- and tripropylene glycols is detected. On the other hand, the content of free propylene oxide is 2.5 mg / kg.

 The biobased carbon content of the mixture is equal to

9.2%.

 These results show that the synthetic propylene glycol contains undesirable impurities that are not contained in the PDO of plant origin, as illustrated in Example 2.

 Example 4 Preparation and Analysis of a Composition Free of Glycerin

 The procedure is identical to Example 1, but replacing the propylene glycol and the glycerol of vegetable origin with PDO of plant origin according to Example 2.

 Results:

 Under the conditions of analysis (sensitivity 0.5 ng / g), no trace of propylene oxide or di- and tripropylene glycols is detected.

 The biobased carbon content of the mixture is equal to

99.8%.

 Example 5: Evaluation of the effectiveness of different e-liquids

The e-liquid compositions prepared in Examples 1 to 4 are evaluated by a trained panel of 10 persons equipped with a Joytech ™ brand cigarette and eCab ™ model (December 2013 model). Each tank is filled with an identical amount of e-liquid (1 ml).

 Also, each panelist blinds a test on the basis of 8 successive puffs spaced 20 seconds and each induced by heating 2 seconds. The evaluation is based on the rating, on a scale of 1 to 10, of the criteria of vapor density and aromatic power felt. The passage from one product to another is done by each panelist as follows: 5 minutes after the last aspiration, the panelist rinses his mouth with 2 glasses of water of 100 ml then quenches with 50 ml of water. A rest period between each assessment is set at 10 minutes.

 The averaged results obtained are collated in the following table:

It is clear that propylene glycol of plant origin (Example 1) has substantially the same properties as synthetic propylene glycol (Example 3). In contrast, PDO (Example 2) has a significantly higher vapor density and aromatic power, which is further increased in the absence of glycerin (Example 4). Compared with synthetic propylene glycol, it also makes it possible to produce e-liquid compositions having a small footprint environmental and free of undesirable impurities such as propylene oxide and its derivatives, or even acrolein.

 Example 6 Influence of the Nature of the Solvent on the Viscosity and Nicotine Concentration Base in E-Liquid Formulations

In a glass mixer equipped with a mechanical stirring precisely mixing 6.00 kg of propylene glycol vegetable (rapeseed) marketed by the company under the Oléon Radianol Reference ^® 4710, USP Pharmacopoeia grade), 4.00 kg of vegetable glycerin (marketed by Oléon under the reference Glycerin 4810, Pharmacopoeial grade USP and PE) and 16.26 g of plant nicotine (marketed by Nicobrand under the reference Nicotine Free Base, Pharmaceutical grade Nicotine> 99%). Stirring of the mixture (50 rpm) is maintained for 20 minutes. Product A is then obtained. A sample of 200 g of A is made for analysis.

 The product A is then similarly carried out to prepare the product B corresponding to a mixture consisting of 5.50 kg of propylene glycol, 4.00 kg of glycerin, 50 g of osmosis water and 162.6 g of nicotine. A sample of 200g of B is made for analysis.

The procedure is identical in the product A to prepare the product C_correspondant to a mixture consisting of 9 837.4 g of 1, 3-propanediol supplied by DuPont & Tate & Lyle LLC under the reference Zemea ^® Propanediol and 162.6 g of vegetable nicotine (marketed by Nicobrand under the reference Nicotine Free Base, Pharmaceutical grade Nicotine> 99%). A sample of 200g of C is made for analysis. The product is finally D consists only of 1,3-propanediol provided by DuPont Tate & Lyle & LLC under reference Zemea ^® propanediol.

 The kinematic viscosity of products A, B, C and D is then measured.

Furthermore, a proton NMR spectrum (Nuclear Magnetic Resonance) is taken on an Avance Brucker brand apparatus (500 MHz), products A, B, C, D previously dissolved in D ₂ 0 (deuterated water). . The goal is to measure the percentage of protonated nicotine in the products. This NMR quantification of the proton is carried out on the basis of a calibration curve covering the protonated nicotine concentration range of between 5 and 95%.

 The results are summarized in the following table:

It appears from these tests that 1,3-propanediol product C, in which no addition of osmosis water has been made, has a very advantageous viscosity (<60 mPa / s), resulting in a fluidity making it easy to fill an electronic cigarette tank.

 On the other hand, the product A has a very high viscosity, greater than 400 mPa / s. This type of viscous solution is not usable as e-liquid since it can not be poured at room temperature into the tank body of an electronic cigarette.

By comparison, thanks to the presence of water, product B has a fluidity comparable to that of products C and D. It corresponds to the currently commercial solutions present on the e-liquid market.

 Therefore, it is clear that 1,3-propanediol makes it possible very advantageously to prepare very fluid e-liquids without having to add osmosis water, thus without preservatives or without having to engage a sterilizing microfiltration.

 In addition, by making it possible to formulate e-liquids without water, 1,3-propanediol ensures the delivery of nicotine in base form (non-protonated) and thus in highly bioavailable form.

 Example 7 Influence of the nature of the solvent on the sensory properties of the e-liquid and the ease of suction of the vapor

 The e-liquid compositions B, C and D prepared in Example 6 are evaluated by a trained panel of 40 persons (male, age between 25 and 49 years), equipped with a Joytech ™ brand cigarette and eCab ™ model (December 2013 model). Each tank is filled with an identical amount of e-liquid (1 ml).

 Also, each panelist performs a blind test on the basis of 8 successive puffs spaced 20 seconds and each induced by heating 2 seconds. The passage from one product to another is done by each panelist as follows: 5 minutes after the last aspiration, the panelist rinses his mouth with 2 glasses of water of 100 ml then quenches with 50 ml of water. A rest period between each assessment is set at 10 minutes. The evaluation is based on the rating, on a scale of 1 to 10, of the following criteria:

1) the feeling of "throat hit", that is to say the effect of internal tingling of the throat classically obtained when a smoker inhales a puff of cigarette, which is also felt when an electronic cigarette user sucks a vapor of e-liquid rich in nicotine,

 2) the ease of aspiration of the e-liquid vapor.

 The averaged results obtained are collated in the following table:

II apparaît clairement que le 1,3 propanediol associé à la nicotine (produit C) induit un « throat hit » supérieur à un produit classique constitué de glycérine, de propylène glycol, d'eau et de nicotine (Produit B) . Enfin, il est très intéressant de souligner que le 1 , 3-propanediol seul (produit D) induit un « throat hit » significatif en absence de nicotine et significativement supérieur au produit B.

It is clear that 1,3-propanediol associated with nicotine (product C) induces a throat hit superior to a conventional product consisting of glycerine, propylene glycol, water and nicotine (Product B). Finally, it is very interesting to note that 1,3-propanediol alone (product D) induces a significant "throat hit" in the absence of nicotine and significantly greater than product B.

 With regard to the ease of aspiration of the induced vapor, again the e-liquids C and D prove to be superior to the product B.

 Example 8: Olfactory and gustative evaluation of 1,3-propanediol formulations with or without nicotine and without glycerol

A formulation based on nicotine and 1,3 propanediol containing 15 mg / ml of nicotine is prepared. This formulation and a formulation comprising 1,3 propanediol are blinded to an evaluation. olfactory by an expert oenologist specialized in tasting and olfactory characterization of beverages and alcohols. The assessment includes several distinct techniques, such as those used in the context of the evaluations of large scale alcohols:

 Phase 1: tasting in the mouth in a neutral tulip glass

 In a first phase, both products were tested in a tulip glass usually used for tasting cognac. For each product, we note the so-called first nose notes and the notes that appear after each evaluation. We then conclude with an evaluation of the notes present in the empty glass.

 On a practical level, each product is left in the glass. First time: the product is poured into the glass and then felt. Second time: the glass is covered with a neutral paper and we feel the glass 12 hours after being left to rest. Third step: the paper is removed from the glass for two days (this operation is carried out when one sips brandies to observe the degradations related to the penetration of the air which generally leads to degradations).

 - Phase 2: tasting on the nose in the palm of your hand

The test product is placed in the palm of the hand. Before this phase, the hands are rinsed with demineralised water so as not to have recurring tastes (skin odor, saponic taste associated with a classic wash or rinsing with tap water to have bleach notes). Then the product is felt, and in a second time the product is heated by a massage action in the palm of the hand - Phase 3: tasting on the tip of the finger and in the mouth.

 A large drop of each product is worn on the finger, then on the tongue. During this phase of work, important shades of taste are observed. This essential step, allows to characterize the product.

 Phase 4: tasting aerosols from the vaporization of products consumed using an electronic cigarette. The equipment used meets the following characteristics:

 BCC clearomizer equipped with a 2.2 ohm resistor,

 - variable voltage battery set at 3.2 V,

 - power output 5.7 watt.

 Each product is tasted in a new clearomizer. At first, it is the notes of pleasure that appear then those of degradation. Then, in a second time, the sensations, in particular the sensations greedy and pleasure are observed. Finally, the evolutions during the vaping phase were also observed, in particular in order to measure if, during different phases of drawing, any differences appear, in particular with a view to measuring a possible degradation of the products during heating.

The results are summarized in the table below:

Conclusions: These olfactory evaluation tests, carried out blindly, show the following points:

 major differences in the same product appear according to the tasting method (nose, mouth and vaping);

 - if 1,3-propanediol is rather mild and round in the mouth, it becomes rather bitter to vaping.

 if the addition of nicotine to 1, 3-propanediol, up to 15 mg / ml, is not detected in the nose, the notes delivered in the mouth and vaping are on the other hand, totally different from those observed with 1, 3- non-nicotine propanediol.

 - Whatever the type of formulation, nicotine or not, the notes detected in the nose or mouth do not predict the heartbeat notes detected during the vaping of the product.

 Example 9 Evaluation of the Thermal Stability of 1,3-propanediol-based Formulations with or Without Nicotine and Glycerol-Free

As part of these tests, the thermal stability of propylene glycol, glycerol, 1,3-propanediol, nicotine and their mixture (formulation containing 15 mg / ml of nicotine) was evaluated. The stability of the products and the possible interaction between nicotine and 1,3-propanediol were evaluated by thermogravimetric (TGA) and differential thermal (DTA) analysis on a Q600 TA Instrument. Thermogravimetric analysis is a method of thermal analysis in which changes in the physical and chemical properties of materials are measured as a function of temperature. ATG can provide information on physical phenomena, such as vaporization or combustion. Similarly, information on chemical phenomena such as dehydration or decomposition can be obtained. By differential thermal analysis (DTA), the study material and an inert reference undergo identical thermal cycles. During the analysis, the temperature difference between the sample and the reference is recorded. These temperature differences followed as a function of time with respect to the inert reference, provide information on the thermal phenomena experienced by the sample, or exothermic or endothermic. The ATD analysis gives, by integration of the Heat Flow curve, the enthalpy values that are called endothermic when there is an energy absorption, or exothermic when there is a release of energy in the form of heat. . The endothermic nature is related to a change of state of the compound (eg vaporization) whereas the exothermic character is induced by decomposition reactions or intra- and intermolecular chemical reactions.

 TA IMPUMENT's Q600 Thermogravimetric Analyzer was used to jointly determine product vaporization temperatures, enthalpy values, and non-vaporized product rates at 350 ° C. The conditions of analysis are as follows:

 - test portion: 50 mg

- open crucible under flow of air 100 ml / min

- heating ramp 10 ° C / min

temperature range: 25 to 350 ° C (temperature conditions representative of normal use as well as misuse of an electronic cigarette). Between each analysis, the apparatus is cleaned by heating at 600 ° C under air flow, to remove any traces of residue. vaporized and deposited on the crucible, the balance arms or the walls of the oven.

The results obtained are shown in the table below:

 (1) endothermic peak

 (2) exothermic peak (reaction and / or decomposition)

Conclusions:

 glycerol vaporizes at 260 ° C with 27.3% uncharacterized residue formation (possibly related to a thermal decomposition product);

 propylene glycol vaporizes at a temperature of 174 ° C. without any thermal decomposition;

 1,3-propanediol vaporizes at a temperature of 189 ° C. without any thermal decomposition;

 the nicotine is vaporized at a temperature of 190 ° C., producing a residue after evaporation of 1.08%, related to the presence in the nicotine of a non-vaporizable heavy compound;

 in a mixture, the 1,3-propanediol and the nicotine vaporize simultaneously at 202 ° C. (1 single peak of vaporization observed in ATD) without giving rise to decomposition and / or without reacting with each other.

It is clear that the total vaporization temperature of glycerol is very far from that of nicotine. Similarly, the evaporation temperature of the propylene glycol is 16 ° C lower than that of nicotine.

 In contrast, the vaporization temperatures of 1,3-propanediol and nicotine alone are almost equivalent. Therefore, a formulation based on 1,3-propanediol and nicotine is perfectly suited to ensure a constant delivery of nicotine in aerosol form unlike glycerol or propylene glycol based formulations or their mixture.

 Finally, 1,3-propanediol is a thermally stable solvent for nicotine that vaporizes without interacting with nicotine.

 Thus, the thermal stability of 1,3-propanediol as well as its absence of hot reaction with nicotine, demonstrate its interest as a basis for the formulation of liquids for personal vaporizers.

Example 10 (Comparative): Evaluation of nicotine stabilization in nicotine base form by RN ^Χ Η It is clearly demonstrated in the literature that the most vaporizable form of nicotine is the nicotine base form, i.e. an unprotected nicotine. Nicotine is indeed a molecule that is very sensitive to the acid-base conditions of its environment. Thus, at acidic pH to neutral, it is present in one or more protonated forms that are difficult to vaporize. On the other hand, at basic pH, nicotine is stabilized in base form easily vaporizable and therefore more suitable to be administered in aerosol form.

Also, in this test, the stabilization of nicotine was evaluated by comparing a nicotine formulation as presently on the market, ie formulated in a propylene glycol mixture. and glycerine to a 1,3-propanediol formulation.

The method employed is based on the use of proton magnetic resonance spectrometry ( ¹ R NMR) analysis. This technique makes it possible to identify the hydrogen atoms in a molecule. The signals obtained are partly a function of the environment in which the hydrogen atoms are considered. Also, this technique was previously used by chemists to characterize matrices containing nicotine, including tobacco. However, these studies were still focused on a portion of the protons of the pyrrolidine ring of nicotine, particularly the methyl group. The latter gives in NMR a characteristic signal whose chemical shift is a function of the acidic or basic pH of the formulation. In this test, the evaluation was extended to other hydrogen atoms characteristic of nicotine and whose chemical shifts are also a function of the pH: in this case the 3 hydrogen atoms of the methyl group, the 3 atoms of hydrogen of the pyrrolidine group (Figure 1, a, b, c) and the 4 hydrogen atoms of the pyridine ring (Figure 1, d, e, f, g).

 Figure 1: target hydrogen atoms of nicotine

The NMR analyzes are carried out using a BRUKER spectrometer of 400 MgHz (Ultrashield Plus magnet) equipped with an Avance III console and a BBOF (broadband + fluorine) probe. In a first step, a calibration was carried out by measuring the chemical shifts of the target hydrogen atoms of nicotine solutions at different pHs of between 1 and 10. For this, deuterated solutions (D ₂ 0) of nicotine 0.5 mg / ml, buffered. For this, place 0.5 ml of the nicotine solution in an NMR tube to which is added 0.2 ml of buffer solution (pH 1 = HCl, pH 7 = phosphate, other pHs = citrate). This calibration allows us to determine the chemical shifts of the target hydrogen atoms over the entire pH range.

 Then the NMR analysis of the following two formulations is carried out:

 - Formulation A: 1,3-propanediol (98.2%) + Nicotine

(1.8%)

 - Formulation B: propylene glycol (53.3%) + glycerol (40.0%) + water (4.9%) + Nicotine (1.8%)

 The results obtained are summarized in the table below:

Formulation Chemical shifts of target protons

 Ha Hb Hc H Hd He Hf Hg

 methyl

 Formulation 3.18 3.02 2.26 2.00 8.34 8.34 7.73 7.33 A

 Formulation 3.28 3.12 2.37 2.09 8.43 8.40 7.81 7.42 B

 Nicotine pH 3, 65 3.29 2.66 2.26 8.42 8.39 7.80 7.38 7

 Nicotine pH 3.38 3.14 2.44 2.18 8.37 8.35 7.75 7.35 8

Nicotine pH 3.17 3.02 2.26 1.99 8.34 8.31 7.72 7.33 10 Conclusions:

 It is clear that the nicotine formulated in 1,3-propanediol exhibits chemical shifts that are almost identical to a nicotine at pH 10, that is, present in unprotonated nicotine base form;

 - Formulated in propylene glycol and glycerine, the nicotine is in an environment with a pH of less than 8, rather between 7 and 8. In fact, at this pH value, the basic and mono-protonated nicotine forms coexist.

 Therefore, the nicotine formulated in 1,3-propanediol is essentially present in its most vaporizable form and is therefore most easily delivered by a personal vaporizer.

 Example 11 (Comparative): Evaluation of the aromatic power and throat hit of flavored and nicotinated formulations based on 1,3-propanediol or propylene glycol.

 2 formulations having the following characteristics are prepared:

 - Formulation A:

 1,3-propanediol: 93.5%

 Aroma of mint provided by the company Charabot under the reference "Mint Green" (reference 8711347): 5%

 Nicotine USP supplied by Alchem: 1.5%

- Formulation B:

 Propylene glycol (synthetic): 93.5%

 Aroma of mint provided by the company Charabot under the reference "Mint Green" (reference 8711347): 5%

 Nicotine USP supplied by Alchem: 1.5%

The e-liquid compositions A and B are evaluated by a trained panel of 20 people (male, age between 25 and 49 years), equipped with an electronic cigarette consisting of i) a tank-atomizer of brand Aspire ™ model Nautilus (tank-atomizer: Pyrex tank associated with a BDC atomizer of 1.6 Ohm, air inlet of variable diameter 0.9 / 1.1 / 1.4 / 1.8 mm) and ii) an Eleaf ™ brand battery, model iStick (2200 mA / h capacity) and variable voltage (3.0 to 5.0 V). As part of the test, the conditions of use are as follows:

 - Formulation volume: 2 ml

 - Voltage: 3.5 V

 - Air inlet diameter: 1.4 mm

 Each panelist blinds a test on the basis of 3 sets of puffs spaced one minute apart, consisting of 4 successive puffs spaced 5 seconds apart and each induced by heating for 2 seconds. The evaluation is based on scoring, on a scale of 1 to 10, the criteria of aromatic power and throat hit. The passage from one product to another is done by each panelist as follows: 5 minutes after the last aspiration, the panelist rinses his mouth with 2 glasses of water of 100 ml then quenches with 50 ml of water. A rest period between each assessment is set at 10 minutes. The key points to evaluate are:

 1) the sensation of throat hit throat, that is to say the effect of internal tingling of the throat classically obtained when a smoker inhales a puff of conventional cigarette. Effect also felt when an electronic cigarette user craves a nicotine-rich aerosol.

 2) the aromatic power felt that reflects the intensity of the aroma cleared and perceived.

The averaged results obtained are collated in the following table: Aromatic Power Feeling Composition

 "Throat Hit" felt

 (Notes 1-10) (Notes 1-10)

Formulation A 8.8 ± 0.9 9.1 ± 0.8

 Formulation B 6.1 ± 1.1 6.5 ± 1.1

Conclusions:

 The nicotine formulation based on 1, 3-propanediol is clearly superior in terms of feeling of throat tingling and aromatic power to a formulation based on propylene glycol;

 These results show that 1,3-propanediol allows a better delivery of nicotine and a potentiating effect of aromas. Thus, 1,3-propanediol advantageously allows in terms of safety and cost, to consider lightened formulations in aroma and nicotine.

 Example 12 (comparative): Evaluation of the thermal stability of glycerinated compositions based on 1,3-propanediol or propylene glycol

 In order to evaluate the possible chemical interactions at high temperatures between the various solvent constituents of the nicotine formulations, the thermal stability of various mixtures based on 1,3-propanediol or propylene glycol, with a variable glycerol content, was evaluated. by ATD-ATG. Thus, these tests were carried out under conditions identical to those of Example 2.

The results obtained are presented below: Formulation (3) ATD ATD Temperature ATG Residue Temperature transformation no

 Vaporization (° C) (2) evaporated at (° C) (1) 350 ° C (%)

20% GV + 80% PG 162-209 301 0.65

 40% GV + 60% PG 162-233 303 1.64

 50% GV + 50% PG 166-239 304 0.85

 60% GV + 40% PG 162-243 303 1.19

 20% GV + 80% PDO 194 ND 0.01

40% GV + 60% PDO 192-235 ND 0.29

50% GV + 50% PDO 195-244 ND 0.15

60% GV + 40% PDO 203-247 ND 0.20

 (1) pic end othermic

 (2) exothermic peak (reaction and / or decomposition)

(3) PG = propylene glycol (synthetic), GV = vegetable glycerol, PDO = 1,3-propanediol

 Conclusions:

 With the exception of the 20% GV-40% PDO mixture, all the mixtures lead to two distinct peaks of vaporization, corresponding to the evaporation of the diol and glycerol;

 the 20% GV-40% PDO mixture leads to a co-vaporization of 1,3-propanediol and glycerol, which constitutes an advantage in terms of homogeneity of the aerosol produced by this mixture;

The set of propylene glycol-based formulations leads to the appearance in ATD of exothermic peaks characteristic of intermolecular reactions. There is therefore hot chemical interaction (303-304 ° C) between the constituents of the formulation. These results are similar to those of Jensen et al (R. Paul Jensen, BS Wentai Luo, J. Pankow, RM Strongin, DH Peyton, Hidden Formaldehyde in E-cigarettes Aerosols, New England Journal of Medicine, 372; 392-3.93, January 22,2015) and Bekki et al (K. Bekki, S. Uchiyama, K Ohta, Y. Inaba, H. Nakagome, N. Kunugita, Carbonyl Compounds Generated from Electronic Cigarettes, Int J, Res Public Health 2014 , 11, 11192-11200) which explain the formation of these by-products. Indeed, the thermolysis of propylene glycol and glycerine leads to the formation of volatile aldehydes such as formaldehyde, acetaldehyde and acrolein, which react in situ with the glycols present in the e-liquids (propylene glycol and glycerol) to form heavy acetal compounds;

 The set of propylene glycol-based formulations leads to the presence of non-vaporizable residues at 350 ° C. corresponding to the formation of heavy secondary compounds whose content is between 0.6 and 1.7%;

 On the other hand, all 1,3-propanediol-based formulations do not lead to exothermic reactions. The constituents of the formulations are therefore stable at high temperature. Unlike propylene glycol, 1,3-propanediol stabilizes glycerol;

 The formulations based on 1,3-propanediol have very low levels of non-vaporizable residues at 350 ° C, between 0.01 and 0.3%.

 In terms of thermal stability, 1,3-propanediol-glycerol formulations are stable unlike propylene glycol-glycerol formulations, which lead to the formation of heavy secondary compounds. As a reminder, the thermal stability of the formulations is an essential pre-requisite of the formulations intended for personal vaporizers, with a view to guaranteeing their innocuity under the conditions of use and misuse of these devices.

Therefore, these results clearly indicate that 1,3-propanediol-associated formulations or no to glycerol, avoid the formation by thermolysis of secondary products such as heavy compounds and volatile toxic aldehydes (acrolein, formaldehyde, acetaldehyde).

Claims

Use of a composition comprising 1,3-propanediol and at least one additive selected from the group consisting of glycerine, nicotine, a nicotine substitute and flavor as an electronic cigarette liquid. 2. Use according to claim 1, characterized in that the composition contains from 0 to 40% by weight, preferably from 0 to 20% by weight, for example from 0 to 5% by weight or from 5 to 20% by weight. of glycerin. 3. Use according to claim 1 or 2, characterized in that the composition has an aroma content of less than or equal to 10% by weight. 4. Use according to any one of claims 1 to 3, characterized in that the composition also contains propylene glycol. 5. Use according to claim 4, characterized in that the propylene glycol is obtained from vegetable raw materials. 6. Use according to any one of claims 1 to 5, characterized in that 1,3-propanediol is obtained from vegetable raw materials. An electronic cigarette liquid composition comprising 1,3-propanediol, as well as at least one compound selected from: nicotine, a nicotine substitute and a flavor. 8. Composition according to claim 7, characterized in that it is free of glycerine. 9. Composition according to claim 7 or 8, characterized in that it also contains propylene glycol, preferably of plant origin. 10. Composition according to any one of claims 7 to 9, characterized in that 1,3-propanediol is obtained from vegetable raw materials. 11. Composition according to any one of claims 7 to 10, characterized in that it does not contain water and / or ethanol. 12. Composition according to any one of claims 7 to 11, characterized in that it has a kinematic viscosity at 20 ° C of less than 200 mPas / s, preferably less than 100 mPa.s, more preferably less than 75 mPa. .s, better, less than 60 mPa.s, said viscosity being greater than 30 mPa.s, preferably greater than 40 mPa.s and more preferably greater than 50 mPa. s. An electronic cigarette containing a composition as claimed in any one of claims 7 to 12. 14. Use of 1,3-propanediol in an electronic cigarette liquid containing or not nicotine, to improve the tingling of the throat felt by a user of said liquid and / or the ease of aspiration of the vapor produced by said liquid . 15. Use of 1,3-propanediol, optionally in the presence of glycerin, in an electronic cigarette liquid to enhance the aromatic potency. 16. Use of 1,3-propanediol, optionally in the presence of glycerine, in an electronic cigarette liquid to limit or suppress the formation of thermolysis co-products. 17. Use of 1,3-propanediol in an electronic cigarette liquid containing nicotine to improve the bioavailability of nicotine. 18. Use of 1,3-propanediol, optionally in the presence of glycerine, in a nicotine-containing electronic cigarette liquid to consistently deliver the nicotine.