A green fruit extract composition and its application in treating chronic obstructive pulmonary disease

Abstract

The present invention provides a green fruit extract composition, which is composed of a green fruit water extract, a green fruit n-hexane extract, and a green fruit ethanol extract in a weight ratio of 4-6:2-4:0.5-2. The green fruit extract composition provided by the present invention has a synergistic effect among the three extracts, and the effect is significantly improved, especially in the treatment of chronic obstructive pulmonary disease.

Description

Technical Field

[0001] The invention belongs to the field of natural medicines and relates to a green fruit extract composition, a preparation method thereof and an application thereof in treating chronic obstructive pulmonary disease. Background Art

[0002] Qingguo is the dried mature fruit of olive, a plant of the olive family. Qingguo, also known as Jianguo, tastes astringent at first, but becomes sweet and delicious after long chewing, leaving an endless aftertaste. It has been a commonly used Chinese medicinal material since ancient times. It is sweet, sour, astringent, warm, flat, and non-toxic in nature. It belongs to the lung and stomach meridians and has the effects of clearing heat, relieving sore throat, removing phlegm, promoting body fluid, strengthening the spleen, and detoxifying. The Chinese medicinal Qingguo is also an important ingredient in many Chinese patent medicines.

[0003] Chinese patent CN116870064A discloses a Chinese medicine composition with antioxidant activity and a preparation method thereof, wherein the raw materials are 10%-15% cinnamon, 20%-25% rose, 25%-30% citronella and 35-40% cloves in percentage by mass, and the composition is prepared by extracting, concentrating, purifying and drying. The composition obtained by the invention has good free radical inhibition effect and obvious antioxidant effect.

[0004] There is no report in the prior art on the use of single-component extract compositions of green fruit for treating diseases. Summary of the invention

[0005] The present invention provides a green fruit extract composition, which is prepared by extracting and enriching functional components in green fruit with different solvents, thereby expanding its application range and effect in preparing drugs for treating respiratory diseases.

[0006] To achieve the above object, the present invention adopts the following technical solution:

[0007] The invention provides a green fruit extract composition, which consists of a green fruit water extract, a green fruit n-hexane extract and a green fruit ethanol extract in a weight ratio of 4-6:2-4:0.5-2.

[0008] Furthermore, the green fruit extract composition is composed of green fruit water extract, green fruit n-hexane extract, and green fruit ethanol extract in a weight ratio of 4-6:2-4:0.5-1.5.

[0009] Furthermore, the green fruit extract composition is composed of green fruit ethanol extract, green fruit n-hexane extract and green fruit ethanol extract in a weight ratio of 5:3:1.

[0010] The preparation method of the green fruit water extract comprises the following steps: mixing green fruit powder according to a solid-liquid ratio of 1g: 10-15mL water, adjusting the pH value to 4-6, controlling the temperature to 70°C-90°C, performing cyclic extraction according to microwave extraction for 8-13min and stirring extraction for 12-16min as one cycle, extracting for a total of 210-300min, separating the solid and the liquid after the extraction, and obtaining the green fruit water extract after the extract is dried, and the filter residue is the green fruit extract powder 1.

[0011] In the preparation method of the green fruit water extract, a pH regulator is used to adjust the pH, the pH regulator is citric acid, and the pH is preferably 5.0-5.5.

[0012] In the preparation method of the green fruit water extract, the solid-liquid ratio is preferably 1g:11-13mL; the extraction time is preferably 220-280min.

[0013] In the preparation method of the green fruit water extract, preferably, the extraction is cyclically performed with microwave extraction for 10 minutes and stirring extraction for 14 minutes; the extraction time is preferably 220-260 minutes.

[0014] The preparation method of the green fruit normal hexane extract comprises the following steps: mixing green fruit extract powder 1 at a solid-liquid ratio of 1 g: 18-23 mL normal hexane, the extraction temperature is 40° C. to 60° C., the stirring extraction time is 70-150 minutes, after the extraction is completed, solid-liquid separation is performed, the extract is dried to obtain the green fruit normal hexane extract, and the filter residue is the green fruit extract powder 2;

[0015] In the above-mentioned method for preparing the green fruit n-hexane extract, the solid-liquid ratio is preferably 1g:20-22mL, and the extraction time is preferably 90-120min.

[0016] The preparation method of the green fruit ethanol extract comprises the following steps: mixing green fruit extract powder 2 according to a solid-liquid ratio of 1 g: 20-28 mL ethanol aqueous solution, the extraction temperature is 70-90° C., cyclic extraction is performed according to microwave extraction for 6-12 minutes and stirring extraction for 12-20 minutes as one cycle, the total extraction time is 300-420 minutes, solid-liquid separation is performed after the extraction is completed, and the extract is dried to obtain the green fruit ethanol extract.

[0017] In the preparation method of the green fruit ethanol extract, the ethanol aqueous solution is 50%-70% ethanol aqueous solution.

[0018] In the preparation method of the green fruit ethanol extract, the solid-liquid ratio is preferably 1g:22-24mL.

[0019] In the preparation method of the green fruit ethanol extract, preferably, the extraction is cyclically performed with microwave extraction for 8 minutes and stirring extraction for 16 minutes as one cycle; the extraction time is preferably 330-390 minutes, preferably 360 minutes.

[0020] The raw material used in the invention is green fruit powder, which is the powder obtained after the green fruit is washed, hot-air dried and crushed.

[0021] The green fruit mentioned does not include western green fruit.

[0022] Research in the present invention shows that the green fruit extract composition provided by the present invention, that is, the green fruit water extract, the green fruit n-hexane extract, and the green fruit ethanol extract are combined in a weight ratio of 4-6:2-4:0.5-2, has excellent efficacy in treating COPD. Compared with any single solvent extract component, the composition provided by the present invention produces a synergistic effect, and its efficacy in treating COPD is significantly improved.

[0023] Another object of the present invention is to provide the use of the green fruit extract composition in the preparation of drugs for treating chronic obstructive pulmonary disease.

[0024] Compared with the prior art, the present invention has the following advantages:

[0025] (1) The present invention uses a specific solvent and a specific process to extract the natural effective ingredients of green fruit for treating the respiratory disease COPD, thereby maximizing the utilization of the active ingredients of green fruit, and the green fruit extract composition prepared has excellent efficacy in treating the respiratory disease COPD.

[0026] (2) The present invention prepares the green fruit extract composition in a specific weight ratio, and the three extracts have a synergistic effect, and the effect is significantly improved. DETAILED DESCRIPTION

[0027] The present invention discloses a green fruit extract composition, a preparation method thereof and an application thereof in treating chronic obstructive pulmonary disease. Those skilled in the art can refer to the contents of the present invention, combine the relevant principles of drug extraction, and appropriately improve the process parameters to achieve the desired effect. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included within the scope of the present invention.

[0028] In order to better understand the present invention but not to limit the scope of the present invention, all the numbers expressing the amount, percentage, and other numerical values ​​used in this application should be understood to be modified by the word "about" in all cases. Each numerical parameter should at least be considered to be obtained based on the reported significant figures and by conventional rounding methods.

[0029] Unless otherwise specified, the experimental methods used in the following examples are all conventional methods; the reagents, materials, etc. used in the following examples, unless otherwise specified, can be obtained from commercial channels.

[0030] Example 1: Green fruit water extract

[0031] 1 kg of green fruit powder was mixed with water at a solid-liquid ratio of 1 g:11 mL, the pH value was adjusted to 5.2 with citric acid solution, the temperature was controlled at 80°C-90°C, and the extraction was carried out in a cycle of microwave extraction for 10 min and stirring extraction for 14 min. The microwave power was 400 W, and the extraction time was 240 min in total. After the extraction, the solid and liquid were separated, and the extract was dried to obtain the green fruit water extract, and the filter residue was the green fruit extract powder.

[0032] Example 2: Green fruit water extract

[0033] 1 kg of green fruit powder was mixed with water at a solid-liquid ratio of 1 g: 13 mL, the pH value was adjusted to 5.5 with citric acid solution, the temperature was controlled at 80°C-90°C, and the extraction was carried out in a cycle of microwave extraction for 10 min and stirring extraction for 14 min. The microwave power was 400 W, and the extraction time was 240 min in total. After the extraction, the solid and liquid were separated, and the extract was dried to obtain the green fruit water extract, and the filter residue was the green fruit extract powder.

[0034] Example 3: Green fruit water extract

[0035] 1 kg of green fruit powder was mixed with water at a solid-liquid ratio of 1 g: 12 mL, the pH value was adjusted to 5.5 with citric acid solution, the temperature was controlled at 80°C-90°C, and the extraction was carried out in a cycle of microwave extraction for 10 min and stirring extraction for 14 min. The microwave power was 360 W, and the extraction time was 240 min in total. After the extraction, the solid and liquid were separated, and the extract was dried to obtain the green fruit water extract, and the filter residue was the green fruit extract powder.

[0036] Example 4: Green fruit water extract

[0037] 1 kg of green fruit powder was mixed with water at a solid-liquid ratio of 1 g: 13 mL, the pH value was adjusted to 6.0 with phosphoric acid solution, the temperature was controlled at 80°C-90°C, and the extraction was carried out in a cycle of microwave extraction for 10 min and stirring extraction for 14 min. The microwave power was 400 W, and the extraction time was 240 min in total. After the extraction, the solid and liquid were separated, and the extract was dried to obtain the green fruit water extract, and the filter residue was the green fruit extract powder.

[0038] Example 5: Green fruit water extract

[0039] 1 kg of green fruit powder was mixed with water at a solid-liquid ratio of 1 g:13 mL, and the pH value was adjusted to 6.5 with citric acid solution. The temperature was controlled at 80°C-90°C and stirred for extraction for 240 min. After the extraction, the solid and liquid were separated, and the extract was dried to obtain the green fruit water extract. The filter residue was the green fruit extract powder.

[0040] Example 6: Green fruit water extract

[0041] 1 kg of green fruit powder was mixed with water at a solid-liquid ratio of 1 g:13 mL, the pH value was adjusted to 5.5 with citric acid solution, the temperature was controlled at 80°C-90°C, and microwave extraction was performed for 240 min with a microwave power of 400 W. After the extraction, the solid and liquid were separated, and the extract was dried to obtain the green fruit water extract, and the filter residue was the green fruit extract powder.

[0042] Example 7: Green fruit water extract

[0043] 1 kg of green fruit powder was mixed with water at a solid-liquid ratio of 1 g: 13 mL, the pH value was adjusted to 5.5 with citric acid solution, the temperature was controlled at 80°C-90°C, and the extraction was carried out in a cycle of microwave extraction for 4 min and stirring extraction for 20 min, for a total of 240 min, with a microwave power of 400 W. After the extraction, the solid and liquid were separated, and the extract was dried to obtain the green fruit water extract, and the filter residue was the green fruit extract powder.

[0044] Example 8: Green fruit water extract

[0045] 1 kg of green fruit powder was mixed with water at a solid-liquid ratio of 1 g: 13 mL, the pH value was adjusted to 5.5 with citric acid solution, the temperature was controlled at 80°C-90°C, and the extraction was carried out in a cycle of microwave extraction for 20 min and stirring extraction for 4 min. The microwave power was 400 W, and the extraction time was 240 min in total. After the extraction, the solid and liquid were separated, and the extract was dried to obtain the green fruit water extract, and the filter residue was the green fruit extract powder.

[0046] Example 9: Green fruit water extract

[0047] The feeding amount of green fruit powder is 50 kg, and the green fruit water extract is prepared according to the method of Example 1 to obtain the filter residue green fruit extract powder 1.

[0048] Example 10: Hexane Extract of Green Fruit

[0049] 1 kg of green fruit extract powder 1 (prepared in Example 9) was mixed with n-hexane at a solid-liquid ratio of 1 g: 20 mL. The extraction temperature was 50°C to 60°C, and the stirring extraction time was 90 min. After the extraction, the solid-liquid was separated, and the green fruit n-hexane extract was obtained after the extract was dried. The filter residue was the green fruit extract powder.

[0050] Example 11: Hexane Extract of Green Fruit

[0051] 1 kg of green fruit extract powder 1 (prepared in Example 9) was mixed with n-hexane at a solid-liquid ratio of 1 g: 22 mL. The extraction temperature was 50°C to 60°C, and the stirring extraction time was 120 min. After the extraction, the solid-liquid was separated, and the green fruit n-hexane extract was obtained after the extract was dried. The filter residue was the green fruit extract powder.

[0052] Example 12: Ethyl acetate extract of green fruit

[0053] 1 kg of green fruit extract powder 1 (prepared in Example 9) was mixed with ethyl acetate at a solid-liquid ratio of 1 g: 20 mL. The extraction temperature was 50°C to 60°C, and the stirring extraction time was 110 min. After the extraction, the solid and liquid were separated, and the extract was dried to obtain the green fruit ethyl acetate extract. The filter residue was the green fruit extract powder.

[0054] Example 13: Petroleum ether extract of green fruit

[0055] 1 kg of green fruit extract powder 1 (prepared in Example 9) was mixed with 60-90 petroleum ether in a solid-liquid ratio of 1 g: 20 mL. The extraction temperature was 50°C to 60°C, and the stirring extraction time was 60 min. After the extraction, the solid and liquid were separated. The green fruit petroleum ether extract was obtained after the extract was dried. The filter residue was the green fruit extract powder.

[0056] Example 14: Hexane Extract of Green Fruit

[0057] 1 kg of green fruit extract powder 1 (prepared in Example 9) was mixed with 20 mL of n-hexane at a solid-liquid ratio of 1 g:20 mL, the extraction temperature was 50°C to 60°C, the stirring extraction time was 50 min, and after the extraction, the solid-liquid was separated, and the extract was dried to obtain the green fruit n-hexane extract, and the filter residue was the green fruit extract powder;

[0058] Example 15: Hexane Extract of Green Fruit

[0059] 25 kg of green fruit extract powder 1 (prepared in Example 9) was added, and green fruit n-hexane extract was prepared according to the method of Example 10, and the filter residue obtained was green fruit extract 2.

[0060] Example 16: Green fruit ethanol extract

[0061] 1 kg of green fruit extract powder 2 (prepared in Example 15) was mixed with 70% ethanol aqueous solution at a solid-liquid ratio of 1 g: 22 mL. The extraction temperature was 70-90° C. The extraction was carried out in a cycle of microwave extraction for 8 min and stirring extraction for 16 min. The microwave power was 250 W and the extraction time was 360 min in total. After the extraction, the solid and liquid were separated and the extract was dried to obtain the green fruit ethanol extract.

[0062] Example 17: Green fruit ethanol extract

[0063] The green fruit extract powder 2 (prepared in Example 15) was mixed with 50% ethanol aqueous solution at a solid-liquid ratio of 1g:24mL. The extraction temperature was 70-90°C. The extraction was cyclically carried out with microwave extraction for 8min and stirring extraction for 16min as one cycle. The microwave power was 250W and the extraction time was 360min in total. After the extraction, the solid and liquid were separated, and the extract was dried to obtain the green fruit ethanol extract.

[0064] Example 18: Green fruit ethanol extract

[0065] The green fruit extract powder 2 (prepared in Example 15) was mixed with 60% ethanol aqueous solution at a solid-liquid ratio of 1g:22mL. The extraction temperature was 70-90°C. The extraction was cyclically carried out with microwave extraction for 8min and stirring extraction for 16min as one cycle. The microwave power was 250W and the extraction time was 360min in total. After the extraction, the solid and liquid were separated, and the extract was dried to obtain the green fruit ethanol extract.

[0066] Example 19: Green fruit ethanol extract

[0067] The green fruit extract powder 2 (prepared in Example 15) was mixed with 90% ethanol aqueous solution at a solid-liquid ratio of 1g:22mL. The extraction temperature was 70-80°C. The extraction was carried out in a cycle of microwave extraction for 8min and stirring extraction for 16min. The microwave power was 250W and the extraction time was 360min in total. After the extraction, the solid and liquid were separated, and the extract was dried to obtain the green fruit ethanol extract.

[0068] Example 20: Green fruit ethanol extract

[0069] The green fruit extract powder 2 (prepared in Example 15) was mixed with 20% ethanol aqueous solution at a solid-liquid ratio of 1g:22mL. The extraction temperature was 70-90°C. The extraction was cyclically carried out with microwave extraction for 8min and stirring extraction for 16min as one cycle. The microwave power was 250W and the extraction time was 360min in total. After the extraction, the solid and liquid were separated, and the extract was dried to obtain the green fruit ethanol extract.

[0070] Example 21: Green fruit ethanol extract

[0071] The green fruit extract powder 2 (prepared in Example 15) was mixed with 60% ethanol aqueous solution at a solid-liquid ratio of 1 g: 22 mL. The extraction temperature was 70-90° C. and the extraction was stirred for 360 min. After the extraction was completed, the solid and liquid were separated, and the extract was dried to obtain the green fruit ethanol extract.

[0072] Example 22: Green fruit ethanol extract

[0073] The green fruit extract powder 2 (prepared in Example 15) was mixed with a 60% ethanol aqueous solution at a solid-liquid ratio of 1 g: 22 mL. The extraction temperature was 70-90° C. The extraction was carried out in a cycle of microwave extraction for 16 min and stirring extraction for 8 min. The microwave power was 150 W and the extraction time was 360 min in total. After the extraction, the solid and liquid were separated, and the extract was dried to obtain the green fruit ethanol extract.

[0074] Example 23: Green fruit extract composition

[0075] According to the proportions in the table below, the green fruit water extract, green fruit n-hexane extract, and green fruit ethanol extract were mixed to prepare a green fruit extract composition.

[0076]

[0077]

[0078] Example 24: Efficacy trial for treating chronic obstructive pulmonary disease

[0079] 1. Experimental animals and administration methods

[0080] 1.1 Experimental animals: Male SD rats (weight 220-260 g), adapted for 1 week, room temperature of about 22-25°C, relative humidity of 40% to 70%.

[0081] 1.2 Trial Drugs

[0082] The green fruit extract composition prepared in Example 23, that is, the green fruit extract composition prepared in Example 23-1 to Example 23-16.

[0083] 1.3 Grouping and modeling

[0084] The mice were randomly divided into a model group and Example 23-1 to Example 23-16, with 10 mice in each group. All mice were required to be modeled.

[0085] Modeling: model group, positive control group, and Example 23-1 to Example 23-16 groups.

[0086] Referring to the literature (Li Hongmei, Cui Dejian, Tong Xin, et al. Establishment of rat COPD model by cigarette fumigation plus tracheal injection of endotoxin and simple cigarette fumigation [J]. Chinese Journal of Pathophysiology, 2002, 18 (7): 808-812), the COPD rat model was established by cigarette fumigation plus tracheal injection of LPS. On the 1st and 14th days, the rats were anesthetized by intraperitoneal injection of 0.3% sodium pentobarbital (30 mg / kg). The rats were fixed on the dissecting table with their heads lowered to expose the trachea. An 18-gauge intravenous cannula needle was quickly inserted into the trachea, the needle core was removed, and 0.2 mL (200 ug / uL) of lipopolysaccharide dissolved in physiological saline was injected with a 1 mL syringe. The rats were then upright and rotated left and right to allow the lipopolysaccharide to be evenly distributed in both lungs. From the 2nd to 28th day (except the 14th day), the rats were divided into groups and placed in a self-made closed box. The rats were smoked with cigarettes for 30 minutes every morning, with 4 cigarettes each time.

[0087] Normal group: 10 mice, no modeling.

[0088] 1.4 Administration

[0089] Starting from the first day after successful modeling, the Example 23-1 to Example 23-16 groups were administered 200 mg / kg of the extract once a day.

[0090] The normal group and the model group were given the same dose of normal saline by gavage for 20 consecutive days.

[0091] After 20 days of administration, the mice were anesthetized with an overdose of ether and killed. The intact lung tissue was removed by dissection immediately and homogenized with a glass homogenizer. The pulmonary ventilation-related factors matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were detected according to the kit method.

[0092] In the pathological state of COPD, the increase in the content of MMP-9 and TIMP-1 causes the increase in bronchial wall thickness and smooth muscle thickness, leading to airflow limitation and pulmonary ventilation inhibition, thus causing dyspnea. Therefore, by detecting these two key indicators, the improvement of pulmonary ventilation after COPD treatment can be evaluated.

[0093] 2. Experimental results

[0094]

[0095]

[0096] Note: Compared with the model group, #P<0.05, ##P<0.01;

[0097] Compared with the normal group, *P<0.05, **P<0.01;

[0098] Compared with Example 23-1, ΔP<0.05, ΔΔP<0.01.

[0099] ①Compared with the rats in the normal control group, the contents of MMP-9 and TIMP-1 in the lung tissues of the rats in the model group were significantly increased, with a very significant difference (P<0.01), indicating that the COPD rat model was successfully established.

[0100] ② Compared with the model control group, the green fruit extract composition prepared in Examples 23-1 to 23-3 can significantly reduce the content of MMP-9 and TIMP-1 in the lung tissue of rats with COPD, with very significant differences (P < 0.01), indicating that the green fruit extract composition prepared in Examples 23-1 to 23-3 can treat COPD.

[0101] ③ Compared with the model control group, the green fruit extract composition prepared in Example 23-4 to Example 23-5 can significantly reduce the content of MMP-9 and TIMP-1 in the lung tissue of rats with COPD, with very significant differences (P < 0.01), indicating that the green fruit extract composition prepared in Example 23-4 and Example 23-5 can treat COPD.

[0102] Compared with Example 23-1, the difference between the green fruit extract compositions prepared in Examples 23-4 to 23-5 lies in the different weight ratios of the green fruit water extract, green fruit n-hexane extract, and green fruit ethanol extract; compared with Example 23-1, the contents of MMP-9 and TIMP-1 in the lung tissues of COPD rats in the Examples 23-4 to 23-5 groups were significantly increased, and both had significant differences (P < 0.05), that is, in terms of the treatment of COPD, the green fruit extract compositions prepared in Examples 23-4 to 23-5 were significantly inferior to the green fruit extract composition prepared in Example 23-1.

[0103] ④ Compared with the model control group, the green fruit extract composition prepared in Example 23-6 can significantly reduce the content of MMP-9 and TIMP-1 in the lung tissue of rats with COPD, both of which have very significant differences (P < 0.01), indicating that the green fruit extract composition prepared in Example 23-6 can treat COPD.

[0104] Compared with Example 23-1, the difference of the green fruit extract composition prepared in Example 23-6 is that the extraction process of the green fruit water extract is different. Compared with Example 23-1, the contents of MMP-9 and TIMP-1 in the lung tissue of COPD rats in the Example 23-6 group were significantly increased, with significant differences (P < 0.05), that is, in the treatment of COPD, the green fruit extract composition prepared in Example 23-6 is significantly inferior to the green fruit extract composition prepared in Example 23-1.

[0105] ⑤ Compared with the model control group, the green fruit extract composition prepared in Example 23-7 to Example 23-8 can significantly reduce the content of MMP-9 and TIMP-1 in the lung tissue of rats with COPD, both of which have very significant differences (P < 0.01), indicating that the green fruit extract composition prepared in Example 23-7 to Example 23-8 can treat COPD.

[0106] Compared with Example 23-1, the difference of the green fruit extract composition prepared in Example 23-7 to Example 23-8 is that ethyl acetate and petroleum ether are used instead of n-hexane to extract the active substance; compared with Example 23-1, the contents of MMP-9 and TIMP-1 in the lung tissue of COPD rats in Example 23-7 to Example 23-8 groups were significantly increased, with significant differences (P < 0.05), that is, in terms of the treatment of COPD, the green fruit extract composition prepared in Example 23-7 to Example 23-8 is significantly inferior to the green fruit extract composition prepared in Example 23-1.

[0107] ⑥ Compared with the model control group, the green fruit extract composition prepared in Example 23-9 can significantly reduce the content of MMP-9 and TIMP-1 in the lung tissue of rats with COPD, with a very significant difference (P < 0.01), indicating that the green fruit extract composition prepared in Example 23-9 can treat COPD.

[0108] Compared with Example 23-1, the difference of the green fruit extract composition prepared in Example 23-9 is that the extraction process of the green fruit ethanol extract is different. Compared with Example 23-1, the contents of MMP-9 and TIMP-1 in the lung tissue of COPD rats in the Example 23-9 group were significantly increased, with significant differences (P < 0.05), that is, in the treatment of COPD, the green fruit extract composition prepared in Example 23-9 is significantly inferior to the green fruit extract composition prepared in Example 23-1.

[0109] ⑦ Compared with the model control group, the green fruit extract composition prepared in Examples 23-10 to 22-13 can significantly reduce the content of MMP-9 and TIMP-1 in the lung tissue of rats with COPD, and there are significant differences (P < 0.05), indicating that the green fruit extract composition prepared in Examples 23-10 to 23-13 can treat COPD.

[0110] Compared with Example 23-1, the difference between the green fruit extract compositions prepared in Examples 23-10 to 22-13 lies in that the extraction processes of green fruit water extraction, green fruit n-hexane extraction, and green fruit ethanol extraction are somewhat different. Compared with Example 23-1, the contents of MMP-9 and TIMP-1 in the lung tissues of COPD rats in the Examples 23-10 to 22-13 groups were significantly increased, and all had very significant differences (P < 0.01), that is, in terms of the treatment of COPD, the green fruit extract compositions prepared in Examples 23-10 to 22-13 are significantly inferior to the green fruit extract composition prepared in Example 23-1.

[0111] ⑧Compared with the model control group, the green fruit water extract of Example 22-14 can reduce the content of MMP-9 and TIMP-1 in the lung tissue of rats with COPD, but there is no significant difference (P>0.05), indicating that the green fruit water extract of Example 23-14 cannot treat COPD.

[0112] ⑨ Compared with the model control group, the green fruit n-hexane extract of Example 22-15 can reduce the content of MMP-9 and TIMP-1 in the lung tissue of rats with COPD, but there is no significant difference (P>0.05), indicating that the green fruit n-hexane extract of Example 22-15 cannot treat COPD.

[0113] ⑩ Compared with the model control group, the green fruit ethanol extract of Example 22-16 can reduce the content of MMP-9 and TIMP-1 in the lung tissue of rats with COPD, but there is no significant difference (P>0.05), indicating that the green fruit ethanol extract of Example 22-16 cannot treat COPD.

[0114] In summary, only the combination of Qingguo water extract, Qingguo n-hexane extract, and Qingguo ethanol extract can produce a synergistic effect to treat COPD; further, only the combination of Qingguo water extract, Qingguo n-hexane extract, and Qingguo ethanol extract in a specific weight ratio can better produce a synergistic effect and better treat respiratory system COPD.

Claims

1. A composition of green fruit extract for treating chronic obstructive pulmonary disease, comprising green fruit water extract, green fruit n-hexane extract, and green fruit ethanol extract in a weight ratio of 4-6:2-4:0.5-2; wherein, The preparation method of the green fruit water extract comprises the following steps: mixing green fruit powder according to a solid-liquid ratio of 1g: 10-15mL water, adjusting the pH value to 4-6, controlling the temperature to 70°C-90°C, performing a microwave extraction cycle of 8-13min and a stirring extraction cycle of 12-16min, extracting for a total of 210-300min, separating the solid and the liquid after the extraction, and drying the extract to obtain the green fruit water extract, and the filter residue is the green fruit extract powder 1; wherein the pH adjuster is citric acid; The preparation method of the green fruit n-hexane extract comprises the following steps: mixing green fruit extract powder 1 at a solid-liquid ratio of 1 g: 18-23 mL n-hexane, the extraction temperature is 40°C-60°C, the stirring extraction time is 70-150 minutes, solid-liquid separation after the extraction is completed, the extract is dried to obtain the green fruit n-hexane extract, and the filter residue is the green fruit extract powder 2; The preparation method of the green fruit ethanol extract comprises the following steps: mixing green fruit extract powder 2 with 20-28 mL of ethanol aqueous solution at a solid-liquid ratio of 1 g: 20-28 mL, the extraction temperature is 70-90° C., cyclic extraction is performed according to microwave extraction for 6-12 min and stirring extraction for 12-20 min as one cycle, the total extraction time is 300-420 min, solid-liquid separation is performed after the extraction is completed, and the green fruit ethanol extract is obtained after the extract is dried; wherein the ethanol aqueous solution is 50%-70% ethanol aqueous solution.

2. The composition of green fruit extract according to claim 1, characterized in that The green fruit extract composition is composed of green fruit water extract, green fruit normal hexane extract and green fruit ethanol extract in a weight ratio of 4-6:2-4:0.5-1.

5.

3. The composition of green fruit extract according to claim 1, characterized in that The green fruit extract composition consists of green fruit ethanol extract, green fruit n-hexane extract and green fruit ethanol extract in a weight ratio of 5:3:

1.

4. The composition of green fruit extract according to claim 1, characterized in that In the preparation method of the green fruit water extract, microwave extraction for 10 minutes and stirring extraction for 14 minutes are used as a cycle of cyclic extraction.

5. The composition of green fruit extract according to claim 1, characterized in that In the preparation method of the green fruit water extract, the extraction time is 220-260 minutes.

6. The composition of green fruit extract according to claim 1, characterized in that In the preparation method of the green fruit water extract, the pH is 5.0-5.

5.

7. Use of any one of the green fruit extract compositions of claims 1 to 6 in the preparation of a drug for treating chronic obstructive pulmonary disease.

Images