阅读说明：本技术 一种电子雾化烟液及其制备方法 (Electronic atomized tobacco liquid and preparation method thereof ) 是由 凌沛学 邵华荣 张成盈 孙婷 曾庆恺 于 2021-08-20 设计创作，主要内容包括：本发明提供了一种电子雾化烟液及其制备方法,所述电子雾化烟液中含有肝素、透明质酸和海藻糖,其中肝素的含量为20～2000IU/g,所述透明质酸的质量百分含量为0.01％～2％,所述海藻糖质量百分含量为0.01％～2％。本发明电子雾化烟液,肝素可在电子雾化吸入过程中起到消炎、溶栓、活血化瘀、缓解哮喘的作用,联合应用透明质酸及海藻糖可同时起到润肺、润喉、保护气管黏膜、减轻炎症、保湿润肺的作用,属于电子烟技术领域。(The invention provides an electronic atomized cigarette liquid and a preparation method thereof, wherein the electronic atomized cigarette liquid contains heparin, hyaluronic acid and trehalose, wherein the content of the heparin is 20-2000 IU/g, the mass percentage of the hyaluronic acid is 0.01-2%, and the mass percentage of the trehalose is 0.01-2%. According to the electronic atomized cigarette liquid, heparin can play a role in diminishing inflammation, dissolving thrombus, promoting blood circulation to remove blood stasis and relieving asthma in the electronic atomization inhalation process, and the combined application of hyaluronic acid and trehalose can play a role in moistening lung, moistening throat, protecting tracheal mucosa, relieving inflammation, preserving moisture and moistening lung, and belongs to the technical field of electronic cigarettes.)

1. An electronic atomization tobacco juice is characterized in that: the electronic atomization cigarette liquid contains heparin, hyaluronic acid and trehalose.

2. The electronically atomized liquid aerosol of claim 1, wherein: the heparin content is 20-2000 IU/g, the hyaluronic acid content is 0.01-2% by mass, and the trehalose content is 0.01-2% by mass.

3. The electronically atomized liquid aerosol of claim 1, wherein: the heparin may be heparin or low molecular heparin, and the low molecular heparin includes enoxaparin sodium, dalteparin sodium, nadroparin calcium, heparine sodium or bemiparin sodium.

4. The electronic atomized liquid cigarette of claim 1, wherein the hyaluronic acid comprises a salt of hyaluronic acid, i.e., sodium hyaluronate or other hyaluronate salts, and the molecular weight of hyaluronic acid is 20kDa to 200 kDa.

5. The electronically atomized liquid aerosol of claim 1, wherein: the electronic atomized cigarette liquid also contains water, propylene glycol, glycerin, nicotine and perfume.

6. The electronically atomized liquid aerosol of claim 5, wherein: the water is deionized water, and the perfume comprises natural perfume and/or synthetic perfume.

7. The electronically atomized liquid aerosol of claim 6, wherein: the perfume comprises one or more of vanillin, ethyl vanillin, maltol, ethyl maltol, propyl octalactone, linalool and methyl cyclopentanone.

8. The electronically atomized liquid aerosol as set forth in any one of claims 1 to 7, wherein: the electronic atomized cigarette liquid comprises, by mass, 20-2000 IU/g of heparin, 0.01-2% of sodium hyaluronate, 0.01-2% of trehalose, 1-20% of deionized water, 20-70% of propylene glycol, 20-70% of glycerol, 0.01-2% of nicotine and 0.001-1% of perfume.

9. The electronically atomized liquid tobacco of claim 8, wherein the method of preparing the electronically atomized liquid tobacco comprises the steps of: mixing deionized water, heparin, sodium hyaluronate or salt thereof and trehalose, and stirring until the mixture is completely dissolved to obtain a solution 1; mixing propylene glycol, glycerol, nicotine and perfume, stirring, and mixing to obtain solution 2; adding the solution 1 into the solution 2, and stirring uniformly to obtain the electronic atomized tobacco liquid.

Technical Field

The invention relates to an electronic cigarette, in particular to an electronic atomized cigarette liquid containing heparin, sodium hyaluronate and trehalose and a preparation method thereof.

Background

Electronic cigarettes are manufactured by converting tobacco tar into a vaporized chemical mixture, i.e., aerosol, which is delivered to the respiratory system by electronic heating means. Aerosols are comprised primarily of particulate matter (both fine and ultrafine particles). When the concentration of the aerosol is high enough, the aerosol can generate stimulation to respiratory tract with different degrees, thereby inducing diseases such as pharyngitis, bronchitis, pneumonia and the like, and particularly inducing acute attack of asthma for patients with bronchial asthma. The risk of asthma attacks on users of e-cigarettes is 2.36 times higher than on those who never use e-cigarettes.

Heparin (Heparin) is known from liver discovery, is mainly found in tissue cells of porcine intestinal mucosa, liver, lung and the like, and is a mucopolysaccharide produced by mast cells in animal connective tissues. Because of its good anticoagulant effect, heparin is one of the commonly used clinical anticoagulant drugs. Heparin is classified into low molecular heparin and standard heparin according to molecular weight, and the low molecular heparin includes enoxaparin sodium, dalteparin sodium, nadroparin calcium, heparine sodium, bemiparin sodium, etc. Heparin has anti-inflammatory and anticomplementary activities, and can regulate various proteases and tryptase, inhibit lymphocyte activity, delay lymphocyte-driven hypersensitive reaction, inhibit mast cell degranulation, and inhibit antigen-induced immediate reaction. At present, a plurality of researches prove that heparin inhalation has certain curative effect on asthma, bronchitis and the like. For example, the children with recurrent asthmatic bronchitis can be treated by heparin aerosol inhalation on the basis of conventional treatment, the levels of IL-4, IL-8 and RANTES in serum can be reduced, the ratios of INF-gamma and CD4+ CD25+ CD127-Treg cells can be increased, and the asthmatic time and the lung rale time can be shortened. The low molecular weight heparin calcium can effectively improve the treatment effect of patients suffering from asthma-chronic obstructive pulmonary disease (ACOS) and effectively improve the blood and gas indexes and the lung function of the patients. Other studies have also shown that heparin has a more beneficial effect in alleviating respiratory tract diseases.

Hyaluronic Acid (HA) is a mucopolysaccharide composed of N-acetylglucosamine and D-glucuronic acid, and is an important component of the extracellular matrix (ECM). The lung is rich in HA, which is synthesized by mesenchymal cells, particularly fibroblasts, and then enters the blood via the lymphatic circulation. Modern medical research HAs shown that HA HAs a number of important functions in the pulmonary ECM: HA HAs the effects of hydrating, maintaining homeostasis, maintaining cellular structure and function, modulating inflammatory responses, affecting tissue repair and remodeling, and protecting lung tissue from damage in respiratory diseases. Animal experiments have shown that aerosol inhalation of HA can treat emphysema and COPD, probably because HA binds to the elastic fibers of the lung and protects them from the direct destructive action of elastase, thus preventing alveolar destruction.

Trehalose is a glucose-derived natural disaccharide found in bacteria, plants, insects, yeasts, fungi and invertebrates. Research has shown that trehalose inhibits lung fibroblast transformation by down-regulating beta-catenin, and that trehalose can inhibit bleomycin-induced alveolar epithelial cell senescence, and the mechanism of trehalose may be related to the down-regulation of two senescence-critical proteins, p53 and PAI-1. Therefore, trehalose also has an important role in the improvement of lung diseases.

Although the polysaccharide compound is researched more in respiratory diseases and protective effects, no published technology is found for applying heparin, trehalose and hyaluronic acid to electronic cigarette atomization inhalation in combination aiming at discomfort caused by electronic cigarette inhalation, such as irritation, pharyngitis, bronchitis, pneumonia and asthma, so as to relieve the discomfort caused by the electronic cigarette inhalation.

Disclosure of Invention

Aiming at the defects of the prior art, the invention provides the electronic cigarette liquid containing heparin, and meanwhile, the sodium hyaluronate and the trehalose are jointly used, so that the three can play a synergistic role in the electronic cigarette liquid inhalation process, the stimulation of the electronic cigarette inhalation on the respiratory tract and the lung is relieved, the inflammation is reduced, the asthma incidence is reduced, the respiratory tract injury is repaired, and the harm of the electronic cigarette liquid inhalation on the body is reduced.

The invention provides electronic atomized cigarette liquid which contains heparin, hyaluronic acid and trehalose.

The content of heparin in the electronic atomized cigarette liquid is 20-2000 IU/g, the mass fraction of hyaluronic acid is 0.01-2%, and the mass fraction of trehalose is 0.01-2%.

The electronic atomized cigarette liquid, the heparin may be heparin or low molecular heparin, and the low molecular heparin includes enoxaparin sodium, dalteparin sodium, nadroparin calcium, heparine sodium or bemiparin sodium.

The electronic atomization cigarette liquid comprises hyaluronic acid salt, namely sodium hyaluronate or other hyaluronate, and the molecular weight of the hyaluronic acid is 20 kDa-200 kDa.

The electronic atomization cigarette liquid can play the roles of diminishing inflammation, dissolving thrombus, promoting blood circulation to remove blood stasis and relieving asthma in the electronic atomization inhalation process.

The sodium hyaluronate can play the roles of moistening lung, moistening throat, protecting tracheal mucosa, relieving inflammation, preserving moisture and moistening lung in the electronic atomization inhalation process.

The electronic atomization cigarette liquid can play a role in moistening lung and relieving cell smoke damage in the electronic atomization inhalation process.

The electronic atomized cigarette liquid also contains nicotine, and also can contain water, propylene glycol, glycerol and spice; the water is deionized water; the perfume comprises natural perfume and/or synthetic perfume, such as one or more of vanillin, ethyl vanillin, maltol, ethyl maltol, propyl octalactone, linalool, methyl cyclopentanone and ionone.

The electronic atomized cigarette liquid is characterized in that: the mass percentage of the water is 1-20 percent; the mass percentage of the propylene glycol is 20-70 percent; the mass percentage of the glycerol is 20-70%.

The electronic atomized cigarette liquid comprises the following components: 20-2000 IU/g of heparin, 0.01-2% of sodium hyaluronate, 0.01-2% of trehalose, 1-20% of deionized water, 20-70% of propylene glycol, 20-70% of glycerol, 0.01-2% of nicotine and 0.001-1% of perfume.

The preparation method of the electronic atomized cigarette liquid is characterized by comprising the following steps:

(1) mixing water, heparin, sodium hyaluronate or salt thereof and trehalose, and stirring until the mixture is completely dissolved to obtain a solution 1;

(2) mixing glycerol, propylene glycol, nicotine and perfume, stirring, and mixing to obtain solution 2;

(3) adding the solution 1 into the solution 2, and stirring uniformly to obtain the electronic atomized tobacco liquid.

The invention has the following advantages:

according to the invention, heparin, sodium hyaluronate and trehalose are added into the electronic atomized cigarette liquid, wherein the heparin can play a role in diminishing inflammation, dissolving thrombus, promoting blood circulation to remove blood stasis and relieving asthma in the electronic atomized inhalation process, the sodium hyaluronate can play a role in moistening lung, moistening throat, protecting tracheal mucosa, relieving inflammation, preserving moisture and moistening lung in the electronic atomized inhalation process, and the trehalose can play a role in moistening lung and relieving cell smoke injury in the electronic atomized inhalation process. By utilizing the synergistic effect of the three components, the smoke generated by heating propylene glycol, glycerin and the like in the electronic cigarette can be obviously relieved to stimulate respiratory tract cells by atomizing the smoke into the respiratory tract, the respiratory tract inflammation is relieved, and the asthma incidence rate is reduced. According to the invention, heparin, sodium hyaluronate and trehalose are added into the electronic atomized cigarette liquid, so that the dryness and irritation of the oral cavity can be simultaneously relieved.

Detailed Description

Example 1

(1) In a stirring tank, heparin (with the potency of 200IU/mg), sodium hyaluronate with the molecular weight of 200kDa and trehalose are added in sequence according to the weight, and after the total weight is supplemented by deionized water, the solution is stirred and dissolved completely at room temperature to obtain a solution 1.

(2) In another stirring tank, sequentially adding propylene glycol, glycerol, perfume and nicotine by weight, stirring at room temperature to dissolve completely to obtain solution 2.

(3) Adding the solution 1 into the solution 2, stirring at room temperature, and mixing uniformly to obtain the electronic atomized cigarette liquid, wherein the electronic atomized cigarette liquid contains 20IU/g of heparin, 0.02% of sodium hyaluronate, 0.04% of trehalose, 9.93% of deionized water, 67.5% of propylene glycol, 22% of glycerol, 0.5% of nicotine and 0.001% of perfume.

Example 2

(1) Adding enoxaparin (with potency of 100IU/mg), sodium hyaluronate with molecular weight of 150kDa, trehalose in a stirring tank in sequence according to weight, supplementing the total weight with deionized water, and stirring at room temperature to dissolve completely to obtain solution 1.

(2) In another stirring tank, sequentially adding propylene glycol, glycerol, perfume and nicotine by weight, stirring at room temperature to dissolve completely to obtain solution 2.

(3) Adding the solution 1 into the solution 2, stirring at room temperature, and mixing uniformly to obtain electronic atomized cigarette liquid, wherein the electronic atomized cigarette liquid contains enoxaparin 50IU/g, sodium hyaluronate 0.05%, trehalose 0.01%, deionized water 9.89%, propylene glycol 44.09%, glycerin 45%, nicotine 0.9%, and perfume 0.009%.

Example 3

(1) Adding enoxaparin (potency 100IU/mg), sodium hyaluronate with molecular weight 100kDa, trehalose in a stirring tank according to weight, supplementing the total weight with deionized water, and stirring at room temperature to dissolve completely to obtain solution 1.

(2) And (3) sequentially adding propylene glycol, glycerol, nicotine and spice according to weight in another stirring tank, and stirring at room temperature to dissolve completely to obtain a solution 2.

(3) Adding the solution 1 into the solution 2, stirring at room temperature, and mixing uniformly to obtain the electronic atomized cigarette liquid, wherein the electronic atomized cigarette liquid contains 100IU/g of enoxaparin, 0.1% of sodium hyaluronate, 0.1% of trehalose, 9.7% of deionized water, 30% of propylene glycol, 58.48% of glycerol, 1.5% of nicotine and 0.02% of perfume.

Example 4

(1) Adding enoxaparin (potency 100IU/mg), sodium hyaluronate with molecular weight of 80kDa, trehalose in a stirring tank according to weight, supplementing the total weight with deionized water, and stirring at room temperature to dissolve completely to obtain solution 1.

(2) And (3) sequentially adding propylene glycol, glycerol, nicotine and spice according to weight in another stirring tank, and stirring at room temperature to dissolve completely to obtain a solution 2.

(3) Adding the solution 1 into the solution 2, stirring at room temperature, and mixing uniformly to obtain the electronic atomized cigarette liquid, wherein the electronic atomized cigarette liquid contains enoxaparin 500IU/g, sodium hyaluronate 0.3%, trehalose 0.3%, deionized water 8.9%, propylene glycol 20%, glycerin 68.9%, nicotine 1%, and perfume 0.1%.

Example 5

(1) Adding enoxaparin (with potency of 100IU/mg), sodium hyaluronate with molecular weight of 50kDa, trehalose in a stirring tank in sequence according to weight, supplementing the total weight with deionized water, and stirring at room temperature to dissolve completely to obtain solution 1.

(2) And (3) sequentially adding propylene glycol, glycerol, nicotine and spice according to weight in another stirring tank, and stirring at room temperature to dissolve completely to obtain a solution 2.

(3) Adding the solution 1 into the solution 2, stirring at room temperature, and mixing uniformly to obtain the electronic atomized cigarette liquid, wherein the electronic atomized cigarette liquid contains 1000IU/g of enoxaparin, 0.5% of sodium hyaluronate, 0.5% of trehalose, 8% of deionized water, 50% of propylene glycol, 37.5% of glycerol, 2% of nicotine and 0.5% of perfume.

Example 6

(1) Adding enoxaparin (with the potency of 120IU/mg), sodium hyaluronate with the molecular weight of 20kDa, trehalose in a stirring tank in sequence according to weight, supplementing the total weight with deionized water, and stirring at room temperature to completely dissolve to obtain a solution 1.

(2) In another stirring tank, sequentially adding propylene glycol, glycerol, nicotine and perfume by weight, stirring at room temperature to dissolve completely to obtain solution 2.

(3) Adding the solution 1 into the solution 2, stirring at room temperature, and mixing uniformly to obtain the electronic atomized cigarette liquid, wherein the electronic atomized cigarette liquid contains enoxaparin of 1500IU/g, sodium hyaluronate of 1%, trehalose of 1%, deionized water of 6.75%, propylene glycol of 40%, glycerin of 48%, nicotine of 1% and perfume of 1%.

Example 7

(1) Adding heparin (with the potency of 100IU/mg), sodium hyaluronate with the molecular weight of 20kDa, trehalose and deionized water in a stirring tank according to the weight in sequence, and then stirring and dissolving completely at room temperature to obtain a solution 1.

(2) And (3) sequentially adding propylene glycol, glycerol, nicotine and spice according to weight in another stirring tank, and stirring at room temperature to dissolve completely to obtain a solution 2.

(3) Adding the solution 1 into the solution 2, stirring at room temperature, and mixing uniformly to obtain the electronic atomized cigarette liquid, wherein the content of heparin is 2000IU/g, the content of sodium hyaluronate is 2%, the content of trehalose is 2%, the content of deionized water is 14%, the content of propylene glycol is 50%, the content of glycerol is 29.4%, the content of nicotine is 0.5%, and the content of perfume is 0.1%.

Comparative example 1

(1) Adding sodium hyaluronate with the molecular weight of 80kDa and trehalose into a stirring tank in sequence according to the weight, supplementing the total weight with deionized water, and then stirring and dissolving completely at room temperature to obtain a solution 1.

(2) And (3) sequentially adding propylene glycol, glycerol, nicotine and spice according to weight in another stirring tank, and stirring at room temperature to dissolve completely to obtain a solution 2.

(3) Adding the solution 1 into the solution 2, stirring at room temperature, and mixing uniformly to obtain the electronic atomized cigarette liquid, wherein the electronic atomized cigarette liquid contains 0.3% of sodium hyaluronate, 0.3% of trehalose, 9.4% of deionized water, 20% of propylene glycol, 68.9% of glycerol, 1% of nicotine and 0.1% of perfume.

Comparative example 2

(1) Deionized water was added to the stirred tank and stirred at room temperature to obtain solution 1.

(2) And (3) sequentially adding propylene glycol, glycerol, nicotine and spice according to weight in another stirring tank, and stirring at room temperature to dissolve completely to obtain a solution 2.

(3) Adding the solution 1 into the solution 2, stirring at room temperature, and mixing uniformly to obtain the electronic atomized cigarette liquid, wherein the electronic atomized cigarette liquid contains 10% of deionized water, 20% of propylene glycol, 68.9% of glycerol, 1% of nicotine and 0.1% of perfume. Experimental study data of the invention

Test example 1: influence of liquid of electronic cigarette on airway smooth muscle cells of rat in inflammatory environment

Obtaining airway smooth muscle cells from SD rat, performing primary culture, selecting cells in logarithmic growth phase, digesting with pancreatin, inoculating appropriate amount of cells into 96-well plate, placing at 37 deg.C and 5% CO₂After 24 hours of culture in an incubator, respectively adding working solution and cell culture medium of electronic cigarette samples with different volumes, after 6 hours of action, adding TNF-alpha (simulating asthma airway inflammatory reaction) into the cell culture solution, and dividing the test into a normal control group (containing no electronic cigarette solution and TNF-alpha), a model control group (the dose of TNF-alpha is 10 mu g/L) and different electronic cigarette solutions(the concentration is 60 mug/I) + TNF-alpha (10 mug/L), after TNF-alpha and electronic cigarette liquid are treated for 72 hours, the expression level of TGF-beta 1 in cell supernatant is detected by adopting an enzyme linked immunosorbent assay, and the result is shown in Table 1.

According to the detection result, the cell proliferation rate of TNF-alpha simulation asthma airway inflammation rat airway smooth muscle cells can be improved by adding heparin into the electronic cigarette liquid, the expression level of TGF-beta 1 capable of inducing asthma immune response and airway inflammation reaction is reduced, and meanwhile, the addition of sodium hyaluronate and trehalose has an important synergistic effect on the effect of heparin.

TABLE 1 measurement results of cell proliferation Rate and TGF-. beta.1 expression

Note: p < 0.05 in comparison with model control group

Test example 2: sensory evaluation of electronic cigarette liquid formula

And (3) establishing a professional sensory evaluation group consisting of 5 persons, and evaluating according to an electronic cigarette liquid sensory quality evaluation scale index method. The evaluation criteria were divided into: the fragrance, miscellaneous gas, irritation, aftertaste, sweet and greasy feeling and fullness are evaluated by 6 indexes, each index is 10 points in total, all indexes are divided into score units by 0.5, and the evaluation indexes and the evaluation results are respectively shown in tables 2 and 3.

TABLE 2 sensory evaluation index of electronic cigarette formula

Table 3 sensory evaluation results of electronic cigarette formulations

According to the sensory evaluation results, the stimulation of the electronic cigarette liquid inhalation can be obviously reduced by adding the heparin into the electronic cigarette liquid, and the addition of the sodium hyaluronate and the trehalose has an important synergistic effect. Although the addition of the heparin, the sodium hyaluronate and the trehalose can not bring the fragrance obviously, the electronic cigarette liquid can achieve better sensory comfort when being used together with spices and the like.

The electronic cigarette liquid added with the heparin, the sodium hyaluronate and the trehalose, which is prepared by the invention, can reduce the stimulation of the electronic cigarette liquid to the respiratory tract, protect the respiratory tract cells and simultaneously achieve better sensory comfort of the electronic cigarette.

The above description is only an example of the present application and is not intended to limit the present application. Various modifications and changes may occur to those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application should be included in the scope of the claims of the present application.