A cigarette Chinese herbal medicine additive and its application in relieving chronic obstructive pulmonary disease caused by long-term smoking

Abstract

The application discloses a Chinese herbal medicine additive in cigarettes and application thereof in relieving chronic obstructive pulmonary disease caused by long-term smoking. The additive is composed of Ophiopogon japonicus, Salvia miltiorrhiza, Thymus vulgaris, Gastrodia elata, Platycodon grandiflorum, Salvia officinalis, Saxifraga stolonifera and Rheum palmatum. The additive prepared from the Chinese herbal medicines has a good protective effect on lung cells and tissues, and can reduce the risk of chronic obstructive pulmonary disease caused by long-term smoking.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of cigarette additives, and particularly relates to a Chinese herbal medicine additive for cigarettes and application thereof in relieving chronic obstructive pulmonary diseases caused by long-term smoking. BACKGROUND

[0002] Chronic obstructive pulmonary diseases (COPD) is mainly manifested as progressive dyspnea and lung function decline, and will develop into chronic pulmonary heart disease after repeated attacks, resulting in severe heart and lung dysfunction, and even functional failure of multiple organs.

[0003] Among the many causes of COPD, smoking is the biggest risk factor, and more than 70% of COPD is caused by smoking. The earlier the age of smoking, the greater the amount of smoking, and the higher the incidence. Studies have shown that smoking cessation can effectively delay the decline in lung function. Cheng Xiansheng et al. advised smoking cessation as an important intervention measure, and after 8 years of intervention experiment, the smoking cessation rate in the intervention area was significantly higher than that in the control area, and further research found that the lung function decline rate in the intervention area was significantly lower than that in the control area; the increase in pulmonary heart disease was significantly less than that in the control area. Community intervention may not affect the mortality rate of pulmonary heart disease in a short period of time, but continuous intervention for several years may have the effect of reducing the mortality rate of pulmonary heart disease. Foreign studies have also shown that controlling smoking is the primary and only intervention measure to prevent COPD.

[0004] At present, the main way to induce COPD model is long-term smoke exposure. Smoking-induced animal COPD model is mainly divided into two stages of acute inflammation aggregation in the early stage and chronic inflammation-induced lung remodeling in the later stage. Cigarette smoke can cause abnormalities in the structure and function of the mucociliary system, cause bronchospasm, directly damage the alveolar epithelium, cause lung vascular endothelial cells and alveolar macrophages to aggregate and activate, and gradually show corresponding pathological and physiological changes. Passive smoking is the main animal model for studying the damage of cigarettes to the lungs.

[0005] Therefore, it is necessary to develop a Chinese herbal medicine cigarette additive capable of relieving chronic obstructive pulmonary diseases caused by long-term smoking. SUMMARY

[0006] The present application aims to provide a cigarette additive made of Chinese herbal medicine, which has good protective effect on lung cells and tissues and can reduce the risk of chronic obstructive pulmonary diseases caused by long-term smoking.

[0007] The present application provides a Chinese herbal medicine additive for cigarettes, which is composed of Ophiopogon japonicus, Salvia miltiorrhiza, Thymus vulgaris, Gastrodia elata, Platycodon grandiflorum, Salvia officinalis, Saxifraga stolonifera and Rheum palmatum.

[0008] Further, the additive is composed of the following weight parts of Chinese herbal medicines: Ophiopogon 20-35 parts, Salvia 20-40 parts, Thyme 10-20 parts, Lophatherum 12-16 parts, Platycodon 10-20 parts, Salvia 8-15 parts, Saxifraga 8-15 parts, and Rhubarb 5-8 parts.

[0009] Further, the additive is composed of the following weight parts of Chinese herbal medicines: Ophiopogon 20-35 parts, Salvia 20-40 parts, Thyme 10-20 parts, Lophatherum 12-16 parts, Platycodon 10-20 parts, Salvia 8-15 parts, Saxifraga 8-15 parts, and Rhubarb 5-8 parts.

[0010] The present application also provides a preparation method of the specific Chinese herbal medicine additive for cigarettes, comprising the following steps:

[0011] (1) Take Ophiopogon and Salvia, mix and crush to 60-100 mesh, soak in 8-16 times weight of water for 2-3 hours, extract at 80-95°C for 1-3 hours, extract twice by the same method, combine the filtrates, concentrate the filtrates to obtain a concentrated solution, cool down, add 80% ethanol, stand for 12-24 hours, centrifuge to obtain a precipitate, dry to obtain a first extract;

[0012] (2) Take Thyme, Lophatherum, Platycodon, Salvia, and Saxifraga, mix and crush to 40-60 mesh, soak in 10-20 times weight of 40% ethanol for 2-3 hours, ultrasonically extract for 30-50 minutes, repeat the extraction twice, combine the filtrates, concentrate the filtrates, dry, and crush to obtain a second extract;

[0013] (3) Take Rhubarb, crush to 60-100 mesh, soak in 8-16 times weight of 60% ethanol for 1-2 hours, extract at 50°C for 1-2 hours, extract twice by the same method, combine the filtrates, concentrate the filtrates to a density of 1.02 g / ml, add hydroxypropyl-β-cyclodextrin under stirring at 30°C, continuously stir for 2-4 hours, evaporate to remove ethanol, dry after concentration, to obtain a third extract;

[0014] (4) Mix the first extract, the second extract, and the third extract, pass through a 40-80 mesh sieve, to obtain the Chinese herbal medicine additive.

[0015] Further, the volume of the 80% ethanol in step (1) is 4-6 times the volume of the concentrated solution.

[0016] Further, the ultrasonication in step (2) is at 50°C and 800W.

[0017] Further, the weight of the hydroxypropyl-β-cyclodextrin in step (3) is 0.4-0.6 times the weight of the Rhubarb.

[0018] The application also provides the use of the Chinese herbal medicine additive in the cigarette in preparation of the cigarette for relieving chronic obstructive pulmonary disease caused by long-term smoking.

[0019] Further, the application method is adding the Chinese herbal medicine additive in the cigarette filter.

[0020] The Chinese herbal medicine additive prepared in the application can significantly improve the decline of lung function (FVC and FEV0.1) caused by long-term smoke exposure, inhibit the increase of inflammatory cell quantity in alveolar lavage fluid, reduce the inflammatory cell infiltration and the formation of pulmonary bulla in lung pathological performance, and further relieve the formation of chronic obstructive pulmonary disease caused by long-term smoking to a certain extent, and reduce the risk of chronic obstructive pulmonary disease caused by long-term smoking. BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1 In the application embodiment 5, the lung tissue pathological sections of smoke exposure for 6 months and 12 months are compared. DETAILED DESCRIPTION

[0022] In order to make the purpose, technical scheme and advantages of the embodiments of the application clearer, the technical scheme in the embodiments of the application will be described clearly and completely below in combination with the drawings in the embodiments of the application. The following embodiments are used to illustrate the application, but not to limit the scope of the application. If the specific technology or condition is not indicated in the embodiments, the technology or condition is carried out according to the technology or condition described in the literature in the art or according to the product instruction.

[0023] Comparative example 1

[0024] The Chinese herbal medicine additive is prepared according to the method described in the example 4 of the patent CN102551207A.

[0025] Comparative example 2

[0026] Ophiopogon japonicus 28 parts, Salvia miltiorrhiza 32 parts, Platycodon grandiflorum 16 parts, Rhubarb 7 parts, and Lophatherum gracile 15 parts are weighed by weight parts, and prepared according to the following method.

[0027] (1) Ophiopogon japonicus, Salvia miltiorrhiza and Rhubarb are mixed and crushed to 80 meshes, 12 times of water by weight is added for soaking for 2 hours, and extracted at 80 DEG C for 2 hours. The same method is used for extraction twice, the filtrate is combined, and the filtrate is concentrated to obtain a concentrated solution. After cooling, 5 times of 80% ethanol by volume of the concentrated solution is added, and the mixture is left to stand for 12 hours. After centrifugation, the precipitate is dried to obtain a first extract;

[0028] (2) Lophatherum gracile and Platycodon grandiflorum are mixed and crushed to 40 meshes, 15 times of 40% ethanol by weight is added for soaking for 2 hours, and extracted by ultrasonic at 50 DEG C and 800 W for 50 minutes. The extraction is repeated twice, the filtrate is combined, and the filtrate is concentrated and dried. The second extract is obtained by crushing.

[0029] (3) The first extract and the second extract are mixed and passed through a 60-mesh sieve to obtain the Chinese herbal medicine additive.

[0030] Comparative Example 3

[0031] Ophiopogon japonicus 28 parts, Salvia miltiorrhiza 32 parts, Platycodon grandiflorum 16 parts, Rheum palmatum 7 parts, Ginkgo biloba 15 parts, Thymus vulgaris 16 parts, and Saxifraga stolonifera 10 parts are weighed out in parts by weight and prepared according to the following method.

[0032] (1) Ophiopogon japonicus, Salvia miltiorrhiza, and Rheum palmatum are mixed and pulverized to 80 mesh, 12 times by weight of water is added for soaking for 2 hours, and extraction is performed at 80°C for 2 hours. The same method is used for extraction twice, the filtrates are combined, the filtrate is concentrated to obtain a concentrated solution, 5 times by volume of 80% ethanol is added to the concentrated solution after cooling, and standing is performed for 12 hours. Centrifugation is performed to obtain a precipitate, which is dried to obtain a first extract;

[0033] (2) Ginkgo biloba, Platycodon grandiflorum, Thymus vulgaris, and Saxifraga stolonifera are mixed and pulverized to 40 mesh, 15 times by weight of 40% ethanol is added for soaking for 2 hours, and extraction is performed at 50°C and 800W for 50 minutes. The same method is used for extraction twice, the filtrates are combined, the filtrate is concentrated and dried, and pulverization is performed to obtain a second extract;

[0034] (3) The first extract and the second extract are mixed and passed through a 60-mesh sieve to obtain the Chinese herbal medicine additive.

[0035] Comparative Example 4

[0036] Ophiopogon japonicus 28 parts, Salvia miltiorrhiza 32 parts, Platycodon grandiflorum 16 parts, Rheum palmatum 7 parts, Ginkgo biloba 15 parts, and Thymus vulgaris 16 parts are weighed out in parts by weight and prepared according to the following method.

[0037] (1) Ophiopogon japonicus, Salvia miltiorrhiza, and Rheum palmatum are mixed and pulverized to 80 mesh, 12 times by weight of water is added for soaking for 2 hours, and extraction is performed at 80°C for 2 hours. The same method is used for extraction twice, the filtrates are combined, the filtrate is concentrated to obtain a concentrated solution, 5 times by volume of 80% ethanol is added to the concentrated solution after cooling, and standing is performed for 12 hours. Centrifugation is performed to obtain a precipitate, which is dried to obtain a first extract;

[0038] (2) Ginkgo biloba, Platycodon grandiflorum, and Thymus vulgaris are mixed and pulverized to 40 mesh, 15 times by weight of 40% ethanol is added for soaking for 2 hours, and extraction is performed at 50°C and 800W for 50 minutes. The same method is used for extraction twice, the filtrates are combined, the filtrate is concentrated and dried, and pulverization is performed to obtain a second extract;

[0039] (3) The first extract and the second extract are mixed and passed through a 60-mesh sieve to obtain the Chinese herbal medicine additive.

[0040] Comparative Example 5

[0041] Ophiopogon japonicus 28 parts, Salvia miltiorrhiza 32 parts, Platycodon grandiflorum 16 parts, Rheum palmatum 7 parts, Ginkgo biloba 15 parts, Saxifraga stolonifera 10 parts, and Salvia officinalis 13 parts are weighed out in parts by weight and prepared according to the following method.

[0042] (1) Take Ophiopogon, Salvia miltiorrhiza, and Rhubarb, mix and crush to 80 mesh, soak in 12 times the weight of water for 2 hours, extract at 80°C for 2 hours, extract twice by the same method, combine the filtrates, concentrate the filtrate to obtain a concentrated solution, cool and add 5 times the volume of 80% ethanol to the concentrated solution, stand for 12 hours, centrifuge to obtain a precipitate, dry to obtain a first extract;

[0043] (2) Take P. quiquefolium, Platycodon, Saxifraga, and Salvia officinalis, mix and crush to 40 mesh, soak in 15 times the weight of 40% ethanol for 2 hours, extract at 50°C and 800W for 50 minutes, repeat the extraction twice, combine the filtrates, concentrate and dry to obtain a second extract;

[0044] (3) Mix the first extract and the second extract, pass through a 60 mesh sieve to obtain a Chinese herbal medicine additive.

[0045] Example 1

[0046] Take 28 parts of Ophiopogon, 32 parts of Salvia miltiorrhiza, 16 parts of Platycodon, 7 parts of Rhubarb, 15 parts of P. quiquefolium, 16 parts of Thyme, 10 parts of Saxifraga, and 13 parts of Salvia officinalis, and prepare according to the following method.

[0047] (1) Take Ophiopogon, Salvia miltiorrhiza, and Rhubarb, mix and crush to 80 mesh, soak in 12 times the weight of water for 2 hours, extract at 80°C for 2 hours, extract twice by the same method, combine the filtrates, concentrate the filtrate to obtain a concentrated solution, cool and add 5 times the volume of 80% ethanol to the concentrated solution, stand for 12 hours, centrifuge to obtain a precipitate, dry to obtain a first extract;

[0048] (2) Take P. quiquefolium, Platycodon, Thyme, Saxifraga, and Salvia officinalis, mix and crush to 40 mesh, soak in 15 times the weight of 40% ethanol for 2 hours, extract at 50°C and 800W for 50 minutes, repeat the extraction twice, combine the filtrates, concentrate and dry to obtain a second extract;

[0049] (3) Mix the first extract and the second extract, pass through a 60 mesh sieve to obtain a Chinese herbal medicine additive.

[0050] Example 2

[0051] Take 28 parts of Ophiopogon, 32 parts of Salvia miltiorrhiza, 16 parts of Platycodon, 7 parts of Rhubarb, 15 parts of P. quiquefolium, 16 parts of Thyme, 10 parts of Saxifraga, and 13 parts of Salvia officinalis, and prepare according to the following method.

[0052] (1) Take Ophiopogon, Salvia miltiorrhiza, mix and crush to 80 mesh, add 12 times the weight of water to soak for 2h, extract at 80℃ for 2h, extract twice in the same way, combine the filtrate, concentrate the filtrate to get a concentrated solution, after cooling, add 5 times the volume of 80% ethanol to the concentrated solution, stand for 12h, centrifuge to get the precipitate, dry to get the first extract;

[0053] (2) Take Pteridium aquilinum, Platycodon grandiflorum, Thymus vulgaris, Saxifraga and Salvia officinalis, mix and crush to 40 mesh, soak in 15 times the weight of 40% ethanol for 2h, extract at 50℃ and 800W for 50min, repeat the extraction twice, combine the filtrate, concentrate and dry to get the second extract;

[0054] (3) Take Rheum palmatum, crush to 80 mesh, add 15 times the weight of 60% ethanol, soak for 2h, extract at 50℃ for 2h, extract twice in the same way, combine the filtrate, concentrate the filtrate to a density of 1.02g / ml, add 3.5 times the weight of hydroxypropyl-β-cyclodextrin at 30℃ with stirring, continuously stir for 4h, evaporate the ethanol, dry after concentration to get the third extract;

[0055] (4) Mix the first extract, the second extract and the third extract, pass through a 60 mesh sieve to prepare the Chinese herbal medicine additive.

[0056] Effect of Chinese herbal medicine additive in Example 3 on the content of harmful substances in smoke

[0057] The Chinese herbal medicine additives prepared in the comparative examples and examples were made into binary composite filter rods at 40mg·cig-1, and were rolled into cigarettes, which were smoked on a Filtrona COA200 cigarette machine (smoking capacity 35ml / min). The content of harmful ingredients TSNAs, PAHs and free radicals in the smoke was determined, and the reduction rate of harmful ingredients was calculated by comparing with cigarettes without adding Chinese herbal medicine additive particles. The results are shown in Table 1.

[0058] Table 1 Reduction rate of harmful substance content in smoke by Chinese herbal medicine additive

[0059] Harmful component reduction rate TSNAs PAHs Free radicals Comparative Example 1 16.5％ 23.6％ 40.8％ Comparative Example 2 12.6％ 28.3％ 42.4％ Comparative Example 3 14.1％ 32.6％ 39.6％ Comparative Example 4 20.5％ 26.8％ 45.9％ Comparative Example 5 16.3％ 25.4％ 51.1％ Example 1 19.6％ 26.8％ 48.3％ Example 2 17.2％ 30.6％ 46.2％

[0060] From Table 1, it can be seen that the Chinese herbal medicine additives prepared in the comparative examples and examples can effectively reduce the content of various harmful ingredients in smoke, including TSNAs, PAHs and free radicals.

[0061] Effect of Chinese herbal medicine additive in Example 4 on lung function and inflammatory cells of rats exposed to smoke for a long time

[0062] The cigarettes added with the Chinese herbal medicine additives prepared in the comparative examples and the examples and the common cigarettes without the Chinese herbal medicine additives are smoked by a smoking machine according to the national standard mode, the mainstream smoke of the cigarettes is introduced into a rat exposure device with air as the carrier gas, the lung function (maximum lung capacity FVC and 0.1s gas exhalation percentage FEV0.1) is detected after smoking for 6 months and 12 months respectively, and the alveolar lavage is performed, the total inflammatory cells and the inflammatory cell classification in the lavage fluid are counted, and the lung tissue is taken for pathological observation. Meanwhile, the air exposure group using air exposure and the common cigarette group without the Chinese herbal medicine additives are set as the controls. The alleviating effect of the Chinese herbal medicine additives on the chronic obstructive pulmonary disease caused by long-term smoking is observed.

[0063] The lung function detection method is as follows: the rats are placed in the smoke exposure system, the common cigarettes without the Chinese herbal medicine additives and the cigarettes added with the Chinese herbal medicine additives are inhaled by the smoking machine, the mainstream smoke is introduced into the smoke exposure system, the control group is exposed to air, after continuous exposure for 6 and 12 months, the rats are anesthetized with sodium pentobarbital, the airway intubation is performed, and the lung function is connected, the maximum lung capacity and the 0.1s gas exhalation amount under the external pressure of 30cmH2O are measured, and the lung function of the rats exposed for 6 and 12 months is detected. N=12, #P<0.05, ##P<0.01 vs the air exposure group; *P<0.05 vs the common cigarette group. The results are shown in Table 2.

[0064] Table 2 Influence of different additives on the lung function indexes FVC and FEV0.1

[0065]

[0066] The results show that after the smoke exposure for 6 and 12 months, the common cigarettes without the Chinese herbal medicine additives show a significant decrease in the maximum lung capacity FVC and the 0.1s gas exhalation percentage FEV0.1 compared with the control group; and the Chinese herbal medicine additives prepared in the examples 1 and 2 significantly improve the decrease in the maximum lung capacity FVC and the decrease in FEV0.1 of the rats caused by long-term exposure.

[0067] Inflammatory cell count in the bronchoalveolar lavage fluid: The rats were placed in the smoke exposure system and inhaled ordinary cigarettes without the Chinese herbal medicine additive and cigarettes with the Chinese herbal medicine additive prepared in Example 2, respectively, by the smoking machine, and were exposed to the smoke for 60 minutes per day. The control group was exposed to air, and the rats were sacrificed after 6 and 12 months of exposure, respectively. The right lower lobe of the lung was fixed, dehydrated, and embedded in wax, and the section was stained with HE to observe the inflammatory cell infiltration and the formation of pulmonary bullae. The results are shown in Table 5.

[0068] Table 3 Effect of different additives on inflammatory cells in the bronchoalveolar lavage fluid (exposure for 6 months)

[0069]

[0070]

[0071] Table 4 Effect of different additives on inflammatory cells in the bronchoalveolar lavage fluid (exposure for 12 months)

[0072]

[0073] The results show that after 6 and 12 months of smoke exposure, the total number of inflammatory cells and the number of macrophages, lymphocytes, and neutrophils in the bronchoalveolar lavage fluid of the ordinary cigarettes without the Chinese herbal medicine additive are significantly increased compared with the control group. The number of inflammatory cells in the bronchoalveolar lavage fluid of the Chinese herbal medicine additive groups prepared in Examples 1 and 2 is significantly improved, indicating that the Chinese herbal medicine additive in the cigarette has a significant alleviating effect on the formation of chronic obstructive pulmonary disease caused by long-term smoking.

[0074] Effect of the Chinese herbal medicine additive on the lung tissue pathology of rats exposed to smoke for a long time in Example 5

[0075] The rats were placed in the smoke exposure system and inhaled ordinary cigarettes without the Chinese herbal medicine additive and cigarettes with the Chinese herbal medicine additive prepared in Example 2, respectively, by the smoking machine, and were exposed to the smoke for 60 minutes per day. The control group was exposed to air, and the rats were sacrificed after 6 and 12 months of exposure, respectively. The right lower lobe of the lung was fixed, dehydrated, and embedded in wax, and the section was stained with HE to observe the inflammatory cell infiltration and the formation of pulmonary bullae. The results are shown in Table 5. Figure 1It can be seen from the figures that the common cigarettes without Chinese herbal medicine additives induce the inflammatory cell infiltration and the formation of pulmonary bulla in the lung tissue sections of the rats after being exposed for 6 months and 12 months, and the cigarettes with Chinese herbal medicine additives improve the inflammatory cell infiltration and the formation of pulmonary bulla in the lung tissue sections of the rats.

Claims

1. A cigarette additive of Chinese herbs for alleviating chronic obstructive pulmonary disease caused by long-term smoking, characterized in that, The additive is composed of Ophiopogon japonicus, Salvia miltiorrhiza, Thymus vulgaris, Ginkgo biloba, Platycodon grandiflorum, Salvia officinalis, Saxifraga stolonifera and Rheum palmatum, and is composed of the following weight parts of Chinese herbal medicines: Ophiopogon japonicus 20-35 parts, Salvia miltiorrhiza 20-40 parts, Thymus vulgaris 10-20 parts, Ginkgo biloba 12-16 parts, Platycodon grandiflorum 10-20 parts, Salvia officinalis 8-15 parts, Saxifraga stolonifera 8-15 parts, and Rheum palmatum 5-8 parts.

2. The method of claim 1, wherein the herbal additive is prepared by mixing the herbal extract and the tobacco extract in a ratio of 1: 1 to 1:

3. It comprises the following steps: (1) Ophiopogon japonicus and Salvia miltiorrhiza are mixed and crushed to 60-100 meshes, 8-16 times the weight of water is added for soaking for 2-3 hours, and 80-95℃ extraction is carried out for 1-3 hours, and the same method is used for extraction twice, and the filtrate is combined and concentrated to obtain a concentrated solution, and after cooling, 80% ethanol is added, and after standing for 12-24 hours, centrifugation is carried out to obtain a precipitate, which is dried to obtain a first extract; (2) Thymus vulgaris, Ginkgo biloba, Platycodon grandiflorum, Salvia officinalis and Saxifraga stolonifera are mixed and crushed to 40-60 meshes, 10-20 times the weight of 40% ethanol is added for soaking for 2-3 hours, and ultrasonic extraction is carried out for 30-50 minutes, and the extraction is repeated twice, and the filtrate is combined and concentrated, and dried and crushed to obtain a second extract; (3) Rheum palmatum is crushed to 60-100 meshes, 8-16 times the weight of 60% ethanol is added for soaking for 1-2 hours, and 50℃ extraction is carried out for 1-2 hours, and the same method is used for extraction twice, and the filtrate is combined and concentrated to a density of 1.02g / ml, and 30℃ stirring is carried out under the addition of hydroxypropyl-β-cyclodextrin, and continuous stirring is carried out for 2-4 hours, and ethanol is evaporated, and after concentration and drying, a third extract is obtained; (4) The first extract, the second extract and the third extract are mixed, and sieved through a 40-80 mesh sieve to obtain a Chinese herbal medicine additive.

3. The method of claim 2, wherein the herbal additive is prepared by mixing the herbal extract with the tobacco extract. The volume of the 80% ethanol in step (1) is 4-6 times the volume of the concentrated solution.

4. The method of claim 2, wherein the herbal additive is prepared by mixing the herbal extract with the tobacco extract. The ultrasonic extraction in step (2) is carried out at 50℃ and 800W.

5. The method of claim 2, wherein the herbal additive is prepared by mixing the herbal extract with the tobacco extract. The weight of the hydroxypropyl-β-cyclodextrin in step (3) is 0.4-0.6 times the weight of Rheum palmatum.

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