LIQUID COMPOSITION FOR INHALATION FOR ELECTRONIC CIGARETTES

Abstract

A liquid composition is for inhalation for electronic cigarettes. A composition for inhalation by electronic cigarette includes the following components: a) water 25-40% by weight, b) 1,3-propanediol 30-50% by weight, c) glycerol 20-30% by weight, d) a preservative 0.1-5% by weight, e) optionally, nicotine 0.2-6% by weight, 0 optionally, a flavouring 0-10% by weight, g) optionally, at least a cycl ? dextrin 0.1-5% by weight.

Claims

1. A composition for inhalation by electronic cigarette that does not contain propylene glycol and that comprises the following components: TABLE-US-00005 a) water 25-40% by weight; b) 1,3-propanediol 30-50% by weight; c) glycerol 20-30% by weight; d) a preservative 0.1-5% by weight

2. The composition according to claim 1, wherein the preservative is sodium benzoate.

3. The composition according to claim 1, wherein the flavourings are chosen from fruit, tobacco, mentholated aromas or mixtures thereof.

4. The composition according to claim 1, comprising cyclodextrins.

5. A composition for inhalation by electronic cigarette that does not contain propylene glycol, comprising the following components: TABLE-US-00006 a) water 29-33% by weight; b) 1,3-propanediol 38-43% by weight; c) glycerol 22-28% by weight; d) a preservative 0.1-5% by weight

6. A kit comprising one or more doses of the composition according to claim 1 and one or more doses of flavourings.

7. An inhalation device containing one or more doses of the composition according to claim 1 with or without doses of flavourings.

8. The composition according to claim 1, comprising one or more of: TABLE-US-00007 e) nicotine 0.2-6% by weight; f) a flavouring 0-10% by weight; g) at least a cyclodextrin 0.1-5% by weight.

9. The composition according to claim 8, wherein the preservative is sodium benzoate.

10. The composition according to claim 8, wherein the flavourings are chosen from fruit, tobacco, mentholated aromas or mixtures thereof.

11. The composition according to claim 8, comprising cyclodextrins.

12. A kit comprising one or more doses of the composition according to claim 8, and one or more doses of flavourings.

13. An inhalation device containing one or more doses of the composition according to claim 8.

14. The inhalation device according to claim 5, comprising one or more doses of flavourings.

15. The composition according to claim 5, comprising one or more of: TABLE-US-00008 e) nicotine 0.2-6% by weight; f) a flavouring 0-10% by weight; g) at least a cyclodextrin 0.1-5% by weight.

16. The composition according to claim 15, wherein the preservative is sodium benzoate.

17. The composition according to claim 15, wherein the flavourings are chosen from fruit, tobacco, mentholated aromas or their mixtures.

18. The composition according to claim 15, comprising cyclodextrins.

19. A kit comprising one or more doses of the composition according to claim 15, and one or more doses of flavourings.

20. An inhalation device containing one or more doses of the composition according to claim 14.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0017] The present invention relates to a base composition for inhalation by electronic cigarette which does not contain propylene glycol and comprising the following components:

TABLE-US-00002 a) water 25-40% by weight b) 1,3-propanediol 30-50% by weight c) glycerol 20-30% by weight d) a preservative 0.1-5% by weight e) optionally, nicotine 0.2-6% by weight f) optionally, a flavouring 0-10% by weight g) optionally, at least 0.1-5% by weight. a cyclodextrin

[0018] The water is preferably purified water FU. Its main function is to modulate the polarity of the aerosol particles, break down the toxicity of the mixture and increase the bioavailability of nicotine.

[0019] The 1,3-propanediol (component b)) acts as a viscosifying agent, increases the share of deprotonated nicotine by increasing the pH of the solution, bind the water particles by modifying the properties of the mixture both biologically and in the tank, and convey the aromas with high efficiency.

[0020] Glycerol (component c)) is preferably vegetable glycerol, whose main function is to modulate the body of the aerosol, defining its hygroscopicity and osmolarity.

[0021] The preservative (component d)) is preferably sodium benzoate.

[0022] Cyclodextrins (component g)) have the function of enhancing aromas and modulating the perception and bioavailability of nicotine.

[0023] The flavorings (component f)) can be of any type normally used for electronic cigarettes, such as fruit, tobacco, mentholated flavors, or mixtures thereof. The flavorings can be added to a base composition which does not contain them directly by the smoker.

[0024] The greater amount of water compared to the compositions for conventional electronic cigarettes allows to decrease the toxicity of the composition.

[0025] The substitution of propylene glycol (used in conventional compositions) with 1,3-propanediol also produces a substantial decrease in the toxicity of the composition. Furthermore, the high amount of water, by modulating the polarity of the aerosol particles, increases the bioavailability of nicotine, making the product extremely effective from the point of view of pharmacokinetics, but in itself an excessive increase in water can lead to malfunctions and losses of liquid from the device. These possible disadvantages are counterbalanced by the presence, in appropriate quantities, of 1,3-propanediol, which by forming hydrogen bonds with water causes a change in the surface tension and a different capillarity behavior.

[0026] In preferred embodiments, the basic composition for inhalation via e-cigarette that does not contain propylene glycol comprises:

TABLE-US-00003 a) water 29-33% by weight b) 1,3-propanediol 38-43% by weight c) glycerol 22-28% by weight d) a preservative 0.1-5% by weight e) optionally, nicotine 0.2-6% by weight f) optionally, a flavouring 0-10% by weight g) optionally, at least 0.1-5% by weight. a cyclodextrin

[0027] Experimental Part

[0028] In order to study the potential skin irritation of the compositions of the invention, a sample of the composition was applied as such to reconstructed human epidermis (RHE), the cell viability of which was then evaluated by MTT test.

[0029] The reconstructed human epidermis consists of normal human keratinocytes grown on an inert polycarbonate filter at the air-liquid interface in a chemically well-defined growth medium.

[0030] The chemical base of the test is the reduction of MTT, a yellow substance in solution, to form purple formazan crystals. Such a reduction process mainly occurs in the mitochondria and is highly dependent on the activity of the mitochondrial enzyme succinate dehydrogenase. As a result of these metabolic processes, purple formazan crystals appear within some hours, which can be dissolved in isopropanol. The absorbance of the solubilized crystals can be measured at the wavelength 540 nm and is proportional to the number of living cells in a very wide linear range.

[0031] The reduction of the cell viability of the tissues treated with the test sample with respect to the negative control is used to predict the potential for skin irritation. For this purpose, 3 RHE tissues were treated with the tested product and 3 were treated with 5% sodium dodecyl sulfate (SDS) (positive control). 3 untreated RHE tissues (kept in D-PBS during the incubation period) were used as a negative control. The tested sample is considered irritating to the skin if the cell viability of the tissues upon the treatment is ?50%.

[0032] The test was performed following the guidelines of UNI EN ISO 10993-10:2013.

[0033] Pre-Incubation

[0034] The RHE tissues were left in growth medium for at least 2 hours (37? C., 5% 002) before treatment.

[0035] Treatment

[0036] The RHE tissues were treated for 15 minutes with 30 ?l of substance according to the following pattern: [0037] Negative control DPBS [0038] Positive control 5% SDS [0039] Tested sample.

[0040] Each experiment was conducted in triplicate.

[0041] Washes

[0042] The RHE tissues were repeatedly washed with DPBS, in order to eliminate all traces of the substances used for the treatments.

[0043] Post-Incubation

[0044] The RHE tissues were transferred to the growth medium for 42?2 hours (37? C., 5% 002).

[0045] MTT Test

[0046] The RHE tissues were treated with MTT (1 mg/ml) for 3 hours ?5 minutes (37? C., 5% CO.sub.2) and then the formazan crystals were extracted in isopropanol for 2 hours ?5 minutes at room temperature. The optical density reading was performed at 540 nm.

[0047] The composition of the invention containing PURIFIED WATER F.U. 30.8%, 1,3-PROPANEDIOL (PDO) 41%, VEGETAL GLYCEROL 28%, GRANULAR SODIUM BENZOATE EP-E 211 0.2% (mg, powder), was tested in the aforesaid MTT test, resulting in a treated tissue vitality percentage of about 100%. Therefore, the base composition of the present invention does not exhibit the cytotoxicity which is typical of compositions for electronic cigarettes based on propylene glycol, thus making the practice of vaping much safer.

[0048] Panel Test with Users

[0049] To assess whether our liquid is more effective than the current electronic cigarette in delivering nicotine, a test was conducted with regular users. The tests were designed involving 16 dual users, ie traditional smokers who also use electronic cigarettes. Since the choice of nicotine concentration is a very subjective parameter, the volunteers were asked to compare the performance of their traditional cigarette with their traditional electronic cigarette and with the composition according to the invention, balancing the nicotine concentration between our liquid and that present in the traditional electronic cigarette.

[0050] The composition according to the invention is the same as the previous example.

[0051] The conventional composition contains an amount of nicotine ranging from 4 to 12 mg/ml with a preference for the concentration of 8 mg/ml.

[0052] The data are shown in the following table I.

TABLE-US-00004 TABLE I Results of test on regular users 1 2 3 4 5 6 7 8 Average PERCEIVED INTENSITY (1 = LITTLE intensE; 8 = VERY intensE cigarette 4 3 9 7.3 Conventional e- 4 9 2 1 5.8*** cigarette composition e-cigarette composition 1 12 3 .sup.6.9 ns .sup.??? of invention THROAT SHOT (1 = little strong; 8 = very strong) cigarette 2 1 8 5 7.2 Conventional e- 8 7 1 6.45** cigarette composition e-cigarette composition 1 2 5 7 1 6.2** NS of invention NICOTINE PERCEPTION SPEED (1 = very slow; 8 = very fast) cigarette 1 9 6 7.45 Conventional e- 10 3 2 1 5.3*** cigarette composition e-cigarette composition 2 3 4 7 .sup.7.1 ns .sup.??? of invention LEVEL OF SATISFACTION (1 = little satisfying; 8 = very satisfying) cigarette 1 6 9 7.6 Conventional e- 4 7 3 2 5.9*** cigarette composition e-cigarette composition 2 3 8 3 6.8** .sup.??? of invention Nicotinic 4 6 8 9 12 contents analyzed (mg) No. samples 2 1 5 2 1

[0053] Cigarette vs Conventional e-cigarette composition or cigarette vs e-cigarette composition of invention [0054] **p<0,001 the difference is statistically significative [0055] p<0,01 the difference is statistically significative [0056] p<0.05 the difference is statistically significative [0057] ns the two products are equivalent.

[0058] Conventional e-cigarette composition vs e-cigarette composition of invention [0059] ???p<0,001 the difference is statistically significative [0060] ??p<0,01 the difference is statistically significative [0061] ?p<0,05 the difference is statistically significative [0062] NS the two products are equivalent.

[0063] The intensity of nicotine is statistically perceived in the same way in the cigarette and in the composition according to the invention and significantly less in conventional compositions.

[0064] The throat shot is perceived significantly less both in the conventional composition and in the composition of the invention than in the cigarette. Conventional composition and composition of the invention do not show significant differences.

[0065] The rate of perception of nicotine is statistically perceived in the same way in the cigarette and in the composition of the invention and significantly less in the conventional composition.

[0066] The level of satisfaction is significantly higher in the cigarette than in the other two products, but the composition of the invention is significantly better than the conventional composition.

[0067] From the above data it therefore appears that the composition of the invention is not only less toxic than conventional compositions for electronic cigarettes, but allows for better availability of nicotine, thus approaching the sensory and general satisfaction performance of a traditional cigarette.

[0068] It is apparent that only a few particular embodiments of the present invention have been described, and those skilled in the art will be able to make all the necessary changes thereto for the adaptation to particular applications, without departing from the scope of protection of the present invention.