CN114831335A - Application of anabasine in atomized electronic delivery product - Google Patents
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- CN114831335A CN114831335A CN202210396414.5A CN202210396414A CN114831335A CN 114831335 A CN114831335 A CN 114831335A CN 202210396414 A CN202210396414 A CN 202210396414A CN 114831335 A CN114831335 A CN 114831335A
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- 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
- A24B15/24—Treatment of tobacco products or tobacco substitutes by extraction; Tobacco extracts
- A24B15/26—Use of organic solvents for extraction
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
- A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
- A24B3/00—Preparing tobacco in the factory
- A24B3/12—Steaming, curing, or flavouring tobacco
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- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
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Abstract
The invention provides an application of anabasine in an atomized electron delivery product. Compared with the prior art, the invention provides a new application of anabasine, the anabasine is mixed with the atomizing agent, the essence and the water to form an atomized solution, the atomized solution adopts free anabasine, no acid is added to adjust the pH value or form salt, the processing technology is simple, nicotine or nicotine salt in the prior art or products is replaced, and the safety is high. The anabasine and the atomizing agent form aerosol to promote release, so that the effective delivery of the anabasine is realized, the experience effect similar to nicotine can be brought, and a selectable new mode is provided for the current atomizing electronic delivery product.
Description
Technical Field
The invention relates to an application of anabasine in an atomized electronic delivery product, belonging to the field of application and addition of electronic delivery products.
Background
The anabasine is similar to nicotine in chemical structure and physical and chemical properties, and is easy to atomize or heat to form aerosol. It also behaves physiologically similar to nicotine, and also acts selectively at nicotinic acetylcholine receptors (nAChRs) of the brain to exert physiological effects. The anabasine is similar to nicotine in structure, physicochemical property and physiological mechanism, so that the anabasine can bring experience effects similar to nicotine to smokers. Anabasine has not been seen to be applied to atomization electronic transmission products independently.
Disclosure of Invention
The invention aims to provide a new application of anabasine in an atomized electronic delivery product, the anabasine is mixed with an atomizing agent, essence and water to form an atomized solution, effective delivery of the anabasine to a human body can be realized through electronic atomization equipment, an experience effect similar to nicotine is brought, and a selectable new mode is provided for the current atomized electronic delivery product.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides an application of anabasine in an atomized electronic delivery product.
Preferably, the anabasine is used in free form.
Preferably, the anabasine comprises (-) -S-anabasine, (-) -R-anabasine or (±) -anabasine.
Preferably, the anabasine is mixed with an atomizing agent, essence and water to form an atomized solution for an atomized electronic delivery product.
Preferably, the atomized solution comprises the following components in percentage by mass:
the anabasine is added into the atomized solution, so that the anabasine is effectively delivered to a human body, an experience effect similar to nicotine can be brought, and the harm of the electronic cigarette to the health of the human body is reduced.
In addition, the anabasine adopted by the invention is in a free form (namely, various organic acid salts are not added), has low toxicity and small irritation, does not need to be added with acid to form salts, has a simple process for preparing the atomized solution, does not generate obvious throat-hitting feeling when used in an atomized electronic delivery product, and ensures that a consumer has better experience when using the atomized electronic delivery product. In addition, free form of anabasine also has the advantages of high transfer rate, easy action on receptor targets through organism tissues, rapid exertion of physiological effect and the like.
The results of the examples show that when the CETI 8V 3.0 electronic cigarette smoking machine is used for smoking, the fixed smoking duration is 3s, the smoking frequency is 30s, the smoking capacity is 55mL, the release amount of anabasine in the atomized steam type electronic cigarette reaches 50-200 mug/puff (the quality of alkaloid in each aerosol in a standard smoking mode), and the requirements of different consumers are met.
The evaluation results of acute and subacute inhalation toxicity of the anabasine and nicotine in rats show that the tolerance dose of human bodies to the inhalation of the anabasine reaches 3.75mg/kg/day and the tolerance dose to the inhalation of the nicotine reaches 1.13mg/kg/day, and compared with the nicotine, the anabasine is higher in biological safety of the human bodies and can replace the nicotine to be used in atomization electronic delivery products.
Drawings
FIG. 1 shows rat mortality during exposure to NIC aerosol inhalation at doses of 87mg/kg, 43.5mg/kg, 26.1mg/kg, and 8.7 mg/kg;
figure 2 is a non-linear fit curve of NIC inhaled dose versus rat mortality results;
FIG. 3 is a graph of rat mortality during exposure to ANA aerosol inhalation doses of 174mg/kg, 130mg/kg, 87mg/kg, 43.5 mg/kg;
FIG. 4 is a non-linear fit curve of ANA inhaled dose versus rat mortality results;
FIG. 5 shows the body weight change of male rats during the subacute toxicity test of ANA;
FIG. 6 shows the body weight change of female rats during the ANA subacute toxicity test;
FIG. 7 shows the feeding changes of male rats during the ANA subacute toxicity test;
FIG. 8 is a graph showing the feeding changes in female rats during the subacute toxicity test of ANA;
FIG. 9 shows the results of histopathological examination of ANA test animals.
Detailed Description
The invention provides an application of anabasine atomized solution in an atomized electron delivery product.
In the invention, the anabasine is preferably mixed with an atomizing agent, essence and water to form an atomized solution for an atomized electron delivery product.
The invention has no special requirements on the mixing process, and can uniformly mix all the components. According to the invention, no acid is added to form salt, the process for preparing the atomized solution is simple, and no throat hitting feeling is generated when the atomized solution is used in an atomized electronic delivery product, so that a better experience feeling is ensured when the atomized solution is used by a consumer on the atomized electronic delivery product.
In the present invention, the atomized solution preferably includes the following components by mass percent:
the atomized solution comprises 1-10% of anabasine by mass percentage, preferably 3-7% of anabasine by mass percentage, and more preferably 3-5% of anabasine by mass percentage. In the examples of the present invention, it is specifically 3% or 5%. In the invention, the anabasine is one or more of (-) -S-anabasine, (-) -R-anabasine and (±) -anabasine.
The atomized solution provided by the invention comprises 80-85% of the atomizing agent, preferably 81-85%, and more preferably 83-85% by mass. In the examples of the present invention, it is specifically 84% or 85%. In the present invention, the atomizing agent is preferably glycerin and/or propylene glycol, more preferably glycerin and propylene glycol. In the invention, when the atomizing agent is glycerol and propylene glycol, the mass ratio of the glycerol to the propylene glycol is preferably (0.5-3): 1, and more preferably (1-1.5): 1. In the invention, the atomizing agent can further promote the release of the anabasine.
The atomized solution provided by the invention comprises 0-3% of essence by mass, preferably 1-3% of essence by mass, and more preferably 2-3% of essence by mass. In the examples of the present invention, it is specifically 3%. In the present invention, the essence plant extract or synthetic essence is used. The invention has no special requirement on the specific types of the essences, and can be selected by the skilled in the art according to the needs.
The atomized solution provided by the present invention includes a balance of water.
In the present invention, the aerosolized electronic delivery product preferably comprises an electronic cigarette.
The invention has no special requirements on the application mode, and the atomized solution is directly heated and atomized to generate aerosol.
The anabasine is small in molecular weight and easy to volatilize, the release of the anabasine is further promoted by the atomizing agent, the anabasine is added into the atomized solution, the effective delivery of the anabasine to a human body is realized, the experience effect similar to nicotine can be brought, and the harm of electronic cigarettes to the health of the human body is reduced.
The following detailed description of an atomized solution and its preparation method and application in atomized electronic delivery products provided by the present invention will be made with reference to the following examples, which should not be construed as limiting the scope of the present invention.
Example 1
Mixing 45mg of anabasine, 1275mg of atomizing agent (glycerol: propylene glycol is 6:4 by mass), 45mg of essence (strawberry essence: mint essence is 1:1 by mass) and 135mg of water to prepare an atomized solution, and heating and atomizing the atomized solution in an electronic atomization device to generate aerosol.
The test is carried out on a CETI 8V 3.0 electronic cigarette smoking machine, an electronic cigarette smoking mode recommended by CORESTA (fixed smoking duration is 3s, smoking frequency is 30s, smoking capacity is 55mL, square wave smoking curve) is adopted, a Cambridge filter disc is adopted to capture aerosol total particulate matters, and GC-FID analysis shows that the release amount of anabasine in the atomizing electronic equipment reaches 105 mug/puff.
Example 2
Mixing 100mg of anabasine, 1600mg of atomizing agent (glycerol: propylene glycol is 6:4 by mass), 60mg of essence (strawberry essence: mint essence is 1:1 by mass) and 240mg of water to prepare an atomized solution, and heating and atomizing the atomized solution in electronic atomization equipment to generate aerosol.
The test is carried out on a CETI 8V 3.0 electronic cigarette smoking machine, an electronic cigarette smoking mode recommended by CORESTA (fixed smoking duration is 3s, smoking frequency is 30s, smoking capacity is 55mL, square wave smoking curve) is adopted, a Cambridge filter disc is adopted to capture aerosol total particulate matters, and the release amount of anabasine in the atomizing electronic equipment reaches 124 mug/puff through GC-FID analysis.
Example 3
Mixing 100mg of anabasine, 1600mg of atomizing agent (glycerol: propylene glycol: 5 mass ratio), 60mg of essence (strawberry essence: black tea: mint essence: 1:1 mass ratio) and 240mg of water to prepare an atomized solution, and heating and atomizing the atomized solution in an electronic atomizing device to generate aerosol.
The test is carried out on a CETI 8V 3.0 electronic cigarette smoking machine, an electronic cigarette smoking mode recommended by CORESTA (fixed smoking duration is 3s, smoking frequency is 30s, smoking capacity is 55mL, square wave smoking curve) is adopted, a Cambridge filter disc is adopted to capture aerosol total particulate matters, and the release amount of anabasine in the atomizing electronic equipment reaches 120 mug/puff through GC-FID analysis.
And (4) performance testing:
the aerosol inhalation half lethal dose (LC50) and the no significant damaging effect dose (NOAEL) of anabasine (ANA) were calculated by an acute inhalation toxicity test on SD rats and compared with the results of acute inhalation toxicity of Nicotine (NIC). On the basis of the acute inhalation toxicity test result, subacute toxicity test research of ANA is further carried out, damage and harm degree of ANA to respiratory tract tissues and the whole body after entering an animal body through a respiratory tract are evaluated, and safety evaluation is provided for application of ANA in an electronic atomization delivery product.
1. Materials and methods
1.1 test substances
ANA with purity not less than 98% and light yellow oily liquid; NIC, purity is greater than or equal to 95%, yellow oily liquid; propylene Glycol (PG); vegetable Glycerol (VG).
1.2 preparation of test articles and test grouping
Blank Control (Sham Control) inhaled air; preparing a negative Control group (Vehicle Control) test sample according to the mass ratio PG: VG of 50: 50; 1% ANA is prepared according to the mass ratio of ANA to PG to VG being 1:49.5: 49.5; 5% of ANA is prepared according to the mass ratio of ANA to PG to VG being 5:47.5: 47.5; 10% of ANA is prepared according to the mass ratio of ANA to PG to VG being 10 to 45 to 55; 15% of ANA is prepared according to the mass ratio of ANA to PG to VG being 15:42.5: 42.5; 20% ANA is prepared according to the mass ratio of ANA to PG to VG to 20 to 40. 1% of NIC is prepared according to the mass ratio of NIC to PG to VG being 1:49.5: 49.5; preparing 3% of NIC according to the mass ratio of NIC to PG to VG being 3:48.5: 48.5; 5% of NIC is prepared according to the mass ratio of NIC to PG to VG being 5:47.5: 47.5; the 10% NIC was prepared at a mass ratio of NIC to PG: VG of 10:45: 55.
1.3 test animals and rearing environments
SPF grade SD rats, male and female. And (3) carrying out adaptation examination after introducing the animals, wherein 2 animals are placed in each cage in an adaptation period, the adaptation time is 12-13 d, and the animals are introduced for health examination and weighed on the same day. The feed is sterilized full-value nutrition powder, water is freely drunk, the temperature of an animal room is 20-25 ℃, the humidity is 45% -70%, the light period is automatically controlled, and the light and shade are respectively 12 hours every day.
1.4 test instruments
HRH-BAG1 impact liquid aerosol generator, HRH-MNE3026 small animal single concentration oral nasal exposure system, Beijing Huilong and science and technology Limited; 3321 pharmaceutical Aerosol particle size spectrometer System, TSI, USA.
1.5 acute toxicity test
Referring to the OECD chemical test guidelines for acute inhalation toxicity tests (NO.403, 2009), 5 rats, male and female, were placed into HRH-MNE3026 small animal single concentration oral-nasal exposure system holders, the holders were mounted on a gas cabinet, the gas cabinet was sealed, and exposed to a blank Control group (Sham Control), a negative Control group (Vehicle Control), 4 ANA test article aerosols (5mg/L), and 4 NIC test article aerosols (5mg/L), and the exposure time of the rats was 4 h. Clinical observations were made during the period of exposure, and the number of deaths and survivals of each group of animals was counted. Surviving rats were then continuously observed for 14 d. LC50 and NOAEL values for the tracheal ANA and NIC inhalations were calculated, respectively.
1.6 subacute toxicity test
Based on the comprehensive evaluation of ANA acute toxicity test, ANA inhalant NOAEL is used as the maximum exposure toxicity dosage, and the ANA inhalant NOAEL is divided into 5 groups according to the body weight by a random grouping method: blank Control (Sham Control), negative Control (Vehicle Control) and ANA high, medium and low dose groups of 10 animals each, male and female. The weight of the animals in the group did not exceed ± 20% of the mean weight at the time of grouping. Respectively placing the animals into HRH-MNE3026 small animal single concentration mouth and nose exposure system fixator, installing the fixator on a toxic gas cabinet, sealing the toxic gas cabinet, and exposing and infecting for 28 days 1 time per day.
Observation of clinical symptoms: the experimental animals were observed for irritation, morbidity and mortality during the 28-day nasal inhalation exposure period, and animal body weight and food intake were measured periodically.
And (3) pathological examination: gross dissection was performed on all surviving animals at the end of the trial. When dissected, animals were subjected to thorough, careful visual observations of the respiratory and metabolic systems (lungs, liver, kidneys, etc.), and gross pathological changes were recorded in detail for each animal.
1.7 data processing and results analysis
Respectively counting the number, symptoms, death and survival of animals in each group and the occurrence frequency of various lesions in gross anatomy and pathological histology examination; and calculating the incidence of the animals of different groups and different sexes and the weight average value and the standard deviation at different time.
2. Results of the experiment
2.1NIC inhalation acute toxicity test
Aerosol concentration, NIC inhalation dose and particle size distribution of the toxicant exposure cabinet during exposure are shown in table 1.
TABLE 1 Aerosol concentration, NIC inhalation dose, and particle size distribution
Note: in table 1, MMAD is the median aerodynamic diameter of aerosol mass and GSD is the geometric standard deviation.
Observation of clinical symptoms: aerosol inhalation doses at NIC were: the dead and moribund animals during exposure to the virus of 87mg/kg, 43.5mg/kg, 26.1mg/kg, 8.7mg/kg reached 92.7%, 67.3%, 10.6%, 2.5%, respectively (see FIG. 1). Non-dead animals were observed continuously for 14d until the end of the experiment with no abnormal changes.
According to the statistics of the inhaled dose and the mortality of rats, Graphpadprism 9.0 is used for carrying out nonlinear fitting (figure 2), the NIC aerosol inhalation LC50 value of SD rats is calculated to be 37.8mg/kg, the NIC aerosol inhalation NOAEL dose of SD rats is calculated to be 7.14mg/kg/day, and the HED value is calculated to be 1.13mg/kg/day according to the conversion coefficient of Human Equivalent Dose (HED).
2.2ANA inhalation acute toxicity test
The aerosol concentration, ANA inhalation dose and particle size distribution of the toxicant exposure cabinet during exposure are shown in table 2.
TABLE 2 Aerosol concentration, ANA inhalation dose, and particle size distribution
Observation of clinical symptoms: the dead and moribund animals reached 84.3%, 52.0%, 6.0%, 1.5% respectively during exposure to the ANA aerosol inhalation doses of 174mg/kg, 130mg/kg, 87mg/kg, 43.5mg/kg, respectively (see FIG. 3). Non-dead animals were observed continuously for 14d until the end of the experiment with no abnormal changes.
According to the statistics of the inhaled dose and the mortality results of rats, the ANA aerosol inhalation LC50 value of SD rats is calculated to be 125mg/kg by nonlinear fitting with Graphpadprism 9.0 (figure 4). The ANA aerosol inhalation NOAEL dose of SD rats was 23.6mg/kg/day, and the Human Equivalent Dose (HED) conversion factor calculated HED was 3.75 mg/kg/day.
2.2 subacute toxicity test
The ANA aerosol inhalation maximum dose for the toxicant exposure cabinet was NOAEL (23.6mg/kg/day) for 63min per exposure, 1 time per day for 28 days. The ANA aerosol concentration, inhaled dose and particle size distribution are shown in table 3.
TABLE 3 Aerosol concentration, ANA inhaled dose, and particle size distribution
Observation of clinical symptoms: subacute inhalation toxicity assessment revealed that there were no statistically significant differences in changes in body weight (FIGS. 5-6), feeding (FIGS. 7-8), organ weight (tables 4-5), etc., in each of the dose groups of the hermaphroditic rats over the 28-day dosing period (P > 0.05).
Bronchoalveolar lavage fluid:
in the bronchoalveolar lavage fluid of each dose group of male and female experimental rats, AM (alveolar macrophage), MONO (monocyte), Lym (lymphocyte), Neut (neutrophil), TP (total protein), ALP (alkaline phosphatase), LDH (lactate dehydrogenase) and the like were detected, and no statistical difference was found in the index (P >0.05) compared with the control group. The test data are shown in tables 6 and 7.
Index (I) | | VehicleControl | 1 |
5 |
10%ANA | |
AM(10 6 ) | 4.54±0.151 | 4.53±0.482 | 4.53±0.157 | 4.53±0.166 | 4.53±0.109 | |
LDH(U/L) | 57.2±5.48 | 57.5±6.39 | 58.1±1.36 | 58.1±7.27 | 58.2±3.53 | |
ALP(U/L) | 80.1±8.05 | 80.6±10.35 | 79.5±9.21 | 80.2±2.34 | 80.1±5.15 | |
ACP(U/dL) | 0.62±0.140 | 0.62±0.289 | 0.63±0.073 | 0.63±0.115 | 0.63±0.338 | |
MONO | 82.19±4.03 | 81.20±1.46 | 80.51±3.22 | 80.13±2.07 | 80.07±1.05 | |
Lym | 5.20±1.21 | 5.19±1.36 | 5.18±1.07 | 5.18±1.58 | 5.17±1.75 | |
Neut | 13.81±3.25 | 14.01±2.87 | 14.31±1.85 | 14.32±4.03 | 14.45±2.90 | |
Tch(mmol/L) | 0.08±0.011 | 0.07±0.017 | 0.07±0.054 | 0.08±0.014 | 0.08±0.032 | |
TP(g/L) | 0.85±0.109 | 0.85±0.451 | 0.86±0.314 | 0.86±0.602 | 0.86±0.246 | |
ALb(g/L) | 0.21±0.037 | 0.20±0.042 | 0.19±0.050 | 0.20±0.011 | 0.20±0.029 |
Index (I) | | VehicleControl | 1 |
5 |
10%ANA | |
AM(10 6 ) | 4.20±0.447 | 4.19±0.089 | 4.19±0.067 | 4.19±0.106 | 4.18±0.120 | |
LDH(U/L) | 56.3±5.48 | 56.1±2.40 | 56.7±2.51 | 56.7±1.59 | 56.9±1.92 | |
ALP(U/L) | 78.2±6.23 | 78.6±4.04 | 78.5±3.19 | 78.6±1.05 | 78.8±2.61 | |
ACP(U/dL) | 0.60±0.113 | 0.61±0.089 | 0.61±0.111 | 0.61±0.078 | 0.61±0.055 | |
MONO | 83.29±2.34 | 83.20±1.53 | 82.51±1.28 | 82.13±1.09 | 82.07±1.78 | |
Lym | 5.15±1.30 | 5.14±1.03 | 5.14±1.21 | 5.14±1.17 | 5.13±1.06 | |
Neut | 12.29±1.75 | 12.50±2.37 | 12.51±1.90 | 12.51±2.29 | 12.52±3.54 | |
Tch(mmol/L) | 0.07±0.021 | 0.07±0.012 | 0.07±0.021 | 0.08±0.004 | 0.08±0.029 | |
TP(g/L) | 0.80±0.043 | 0.81±0.030 | 0.81±0.116 | 0.81±0.703 | 0.82±0.099 | |
ALb(g/L) | 0.21±0.042 | 0.21±0.015 | 0.20±0.022 | 0.20±0.040 | 0.20±0.038 |
Index of hematology
When different hematology indexes of different dosage groups of male and female test animals are examined, no obvious difference is found in each index (P >0.05), and the results are shown in tables 8 and 9.
Index (I) | ShamControl | VehicleControl | 1%ANA | 5%ANA | 10%ANA |
WBC(10 9 /L) | 4.52±0.75 | 4.45±0.32 | 4.40±0.40 | 4.39±0.51 | 4.38±0.73 |
RBC(10 12 /L) | 8.60±0.38 | 8.59±0.22 | 8.59±0.31 | 8.58±0.45 | 8.60±0.09 |
HGB(g/dL) | 15.6±0.41 | 15.6±0.20 | 15.7±0.18 | 15.7±0.39 | 15.8±0.71 |
HCT(%) | 47.1±1.67 | 47.2±0.59 | 47.2±1.52 | 47.2±3.06 | 47.2±4.93 |
MCV(fL) | 54.2±2.11 | 54.0±1.15 | 54.4±2.03 | 54.5±1.16 | 54.6±1.33 |
MCH(pg) | 18.1±2.04 | 18.1±1.72 | 18.2±0.92 | 18.1±1.19 | 18.2±2.22 |
PLT(10 9 /L) | 1052±38 | 1051±87 | 1050±65 | 1050±72 | 1050±13 |
Neut(10 9 /L) | 1.06±0.11 | 1.07±0.25 | 1.08±0.20 | 1.08±0.35 | 1.09±0.67 |
Lymph(10 9 /L) | 3.05±0.79 | 3.00±0.46 | 3.01±0.11 | 3.00±0.18 | 2.99±0.85 |
Mono(10 9 /L) | 0.20±0.05 | 0.20±0.07 | 0.19±0.01 | 0.19±0.02 | 0.18±0.05 |
Eos(10 9 /L) | 0.06±0.01 | 0.06±0.03 | 0.06±0.01 | 0.06±0.02 | 0.06±0.04 |
Baso(10 9 /L) | 0.05±0.02 | 0.05±0.01 | 0.05±0.03 | 0.04±0.01 | 0.04±0.02 |
RET(10 9 /L) | 196±22.7 | 196±30.5 | 197±12.1 | 198±20.1 | 199±10.4 |
APTT(s) | 12.7±4.71 | 12.7±1.05 | 12.9±3.03 | 12.7±3.85 | 12.8±4.00 |
Fbg(g/L) | 2.23±0.71 | 2.22±0.33 | 2.21±0.59 | 2.22±0.12 | 2.23±0.03 |
PT(s) | 10.6±0.66 | 10.3±0.52 | 10.2±0.13 | 10.2±0.28 | 10.0±0.15 |
TT(s) | 54.1±3.21 | 54.2±1.03 | 54.1±1.63 | 54.0±0.65 | 54.1±1.17 |
Histopathological examination:
after the test, the test animal tissues were sliced, and HE staining of tissues such as liver, heart, spleen, lung, kidney, etc. was performed for pathological examination (fig. 9, magnification is 100 times), and no significant pathological change was observed in the animal tissues of the control group (sham control and vehicle control) and the high dose group (10% ANA).
In conclusion, rats in different groups have no statistically significant difference in body weight, food intake, organ weight, etc. (P >0.05), and no abnormal change related to the tested substances is shown in the examination of blood, urine, bronchoalveolar lavage fluid, histopathology, etc.
The human ANA inhalation HED value is 3.75mg/kg/day and the human NIC inhalation HED value is 1.13mg/kg/day respectively calculated according to the conversion of Human Equivalent Dose (HED). Comparing the results of the ANA and NIC inhalation exposure toxicology studies in SD rats together, ANA is more biosafety for use in aerosolized electronic delivery products than NIC. The anabasine is an active additive component with low toxicity and high safety, and can be suitable for atomizing electronic delivery products.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (5)
1. Use of anabasine in atomized electron delivery products.
2. Use according to claim 1, wherein said anabasine is used in free form.
3. Use according to claim 1 or 2, characterized in that said anabasine comprises (-) -S-anabasine, (-) -R-anabasine or (±) -anabasine.
4. The use according to claim 1 or 2, wherein the anabasine is mixed with an atomizing agent, a perfume and water to form an atomized solution for use in an atomized electron delivery product.
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JP2022131356A JP7436587B2 (en) | 2022-04-15 | 2022-08-19 | Atomizing solutions used in atomized electronic delivery products |
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