Composition for treating pulmonary tuberculosis as well as preparation method and application thereof

Abstract

The invention discloses a composition for treating pulmonary tuberculosis as well as a preparation method and application thereof, belongs to the technical field of tuberculosis treatment, and provides a composition for treating pulmonary tuberculosis. Comprising the following components in parts by weight: 20-24 parts of radix polygonati officinalis, 15-30 parts of dendrobe, 4-6 parts of sea buckthorn fruit alcohol extract, 8-10 parts of radix bupleuri, 23-27 parts of radix trichosanthis, 5-7 parts of rhizoma phragmitis, 14-18 parts of codonopsis pilosula, 5-9 parts of dogwood, 4-6 parts of asarum, 2-3 parts of andrographis paniculata and 1-3 parts of periostracum cicada. The composition for treating pulmonary tuberculosis can achieve the technical effect of quickly taking effect on treating pulmonary tuberculosis, and does not cause excessive medication burden on liver and kidney.

Description

Technical Field

[0001] The invention belongs to the technical field of tuberculosis treatment, and in particular relates to a composition for treating pulmonary tuberculosis and a preparation method and application thereof. Background Art

[0002] Pulmonary tuberculosis, also often referred to as "pulmonary tuberculosis", is an infectious respiratory disease caused by infection with Mycobacterium tuberculosis. The disease mainly forms lesions in the lung tissue, trachea, bronchi and pleura. The mortality rate of patients is high. People susceptible to this disease include elderly people with low immunity, HIV-infected people, diabetics, pneumoconiosis patients, immunosuppressant users, etc. Common symptoms of pulmonary tuberculosis include persistent cough, sputum, hemoptysis, low fever in the afternoon, night sweats, irregular menstruation or amenorrhea. However, infected people do not necessarily get sick. After the immune system of most infected people eliminates most of the Mycobacterium tuberculosis, a small amount of bacteria will enter the lungs and go dormant. The main way of transmission of tuberculosis is through droplets in the air. Inhalation of droplets containing Mycobacterium tuberculosis can cause infection.

[0003] At present, the treatment of pulmonary tuberculosis is mainly based on Western medicine. Drug treatment is the most important means of treating tuberculosis. The most common tuberculosis drugs are isoniazid, rifampicin (rimatan), ethambutol, pyrazinamide and streptomycin, which have a strong inhibitory and clearing effect on Mycobacterium tuberculosis. However, there are cases where the drug treatment effect is poor or the condition is serious, and it is necessary to consider whether it is drug-resistant tuberculosis. The commonly used drugs for drug-resistant tuberculosis are not effective. In the treatment of pulmonary tuberculosis with traditional Chinese medicine, the pathogenesis is tuberculosis erosion of the lungs. The treatment is based on tonifying deficiency and nourishing the essence, and anti-tuberculosis and killing insects. Baozhen Decoction in "Ten Medicines Divine Book" by Ge Kejiu in the Yuan Dynasty, Baihe Gujin Decoction in "Zhou Shenzhai's Posthumous Book" written by Zhou Zhiqian in the Ming Dynasty, and Yuehua Pills in "Medical Heart Enlightenment" by Cheng Zhongling in the Qing Dynasty are all good prescriptions for tonifying deficiency and nourishing the essence for patients with pulmonary tuberculosis. In the study of the compatibility rules of prescriptions for the treatment of pulmonary tuberculosis, it was found that among the prescriptions for anti-tuberculosis in ancient and modern times, the most frequently used drugs are tonic drugs, but the ancient prescriptions tend to replenish qi, while the modern prescriptions tend to nourish yin. However, the existing traditional Chinese medicines also have the disadvantages of long treatment cycles and easy prolongation of the disease, and more effective traditional Chinese medicine preparations for the treatment of pulmonary tuberculosis are still needed. Summary of the invention

[0004] In order to solve the above technical problems, the present invention proposes a composition for treating pulmonary tuberculosis, a preparation method and an application thereof, so as to achieve the technical effect of rapidly treating pulmonary tuberculosis without causing excessive drug burden on the liver and kidneys.

[0005] To achieve the above object, the present invention provides a composition for treating pulmonary tuberculosis, comprising the following components in parts by weight:

[0006] 20-24 parts of Polygonatum odoratum, 15-30 parts of Dendrobium officinale, 4-6 parts of seabuckthorn fruit alcohol extract, 8-10 parts of Bupleurum chinense, 23-27 parts of Radix Trichosanthis, 5-7 parts of Phragmites australis, 14-18 parts of Codonopsis pilosula, 5-9 parts of Cornus officinalis, 4-6 parts of Asarum, 2-3 parts of Andrographis paniculata, and 1-3 parts of Periostracum Cicadae.

[0007] Polygonatum odoratum: nourishes yin and moistens dryness, promotes the production of body fluid and quenches thirst. Used for lung and stomach yin damage, dry heat cough, dry throat and thirst, internal heat and thirst.

[0008] Dendrobium: nourishes the stomach and produces fluid, nourishes yin and clears heat. It is used for damage to body fluid caused by febrile disease, dry mouth and thirst, insufficient stomach yin, poor appetite and dry retching, persistent heat after illness, yin deficiency and excessive fire, bone steaming and fatigue fever, blurred vision, and weakness of tendons and bones.

[0009] Sea buckthorn fruit alcohol extract: Antioxidant effect, scavenging free radicals; Sea buckthorn fruit alcohol extract is rich in various antioxidants, such as vitamin C, vitamin E, carotenoids, etc., which can effectively scavenge free radicals in the body, delay cell aging, and protect cells from oxidative damage; Anti-inflammatory effect, by reducing the production of inflammatory mediators and alleviating inflammatory responses, it helps to prevent and treat inflammatory diseases; Enhance immunity, sea buckthorn fruit alcohol extract can enhance the body's immune function, improve the body's resistance, and prevent infection and disease; Anti-liver damage, sea buckthorn fruit alcohol extract has obvious liver protection effect, can reduce liver damage caused by chemicals, alcohol, etc., and promote the repair and regeneration of liver cells; Detoxification effect, by enhancing the liver's detoxification function, it helps to eliminate toxins in the body.

[0010] Bupleurum: Reconciles the exterior and interior, relieves liver qi and depression, raises yang and lifts depression, reduces fever and stops malaria. Used for colds and fever, alternating cold and heat, chest and flank pain, irregular menstruation, uterine prolapse, and rectal prolapse.

[0011] Radix Trichosanthis: Clears away heat and purges fire, promotes the production of body fluids and quenches thirst, reduces swelling and discharges pus. Treats thirst caused by fever, dry cough due to lung heat, thirst caused by internal heat, and swelling and toxicity of sores and ulcers.

[0012] Reed root: clears away heat and purges fire, promotes the production of body fluids and quenches thirst, relieves restlessness, stops vomiting, and promotes urination. It is used for thirst due to fever, dry cough caused by lung heat, thirst caused by internal heat, and swelling caused by sores.

[0013] Codonopsis: It can replenish qi, quench thirst, strengthen the spleen and lungs, nourish blood and produce body fluid. It is used for spleen and lung qi deficiency, poor appetite and fatigue, cough and asthma, qi and blood deficiency, sallow complexion, palpitations and shortness of breath, thirst due to loss of body fluid, and internal heat and thirst.

[0014] Cornus officinalis: nourishes the liver and kidneys, astringes and consolidates. Used for vertigo and tinnitus, soreness of waist and knees, impotence and spermatorrhea, enuresis and frequent urination, metrorrhagia and leukorrhea, profuse sweating and collapse, internal heat and thirst.

[0015] Asarum: dispels cold, dispels wind and relieves pain, clears the orifices, warms the lungs and transforms fluid. Colds, headaches, toothaches, rheumatic pain, sinusitis, and coughs caused by lung cold.

[0016] Andrographis paniculata: clears away heat and detoxifies, cools blood and reduces swelling. Used for colds and fever, sore throat, mouth sores, sudden cough, diarrhea, dysentery, hot and painful stranguria, carbuncle, sore, snake and insect bites.

[0017] Cicada shell: dissipates wind and heat, promotes lung function, and calms spasms. It is used for anticonvulsant, sedation, reducing skeletal muscle tension, blocking ganglia, relieving bronchial smooth muscle spasms, and anti-allergic.

[0018] Preferably, the seabuckthorn fruit alcohol extract is obtained by extracting seabuckthorn dried fruit with an ethanol solution.

[0019] The present invention also provides a method for preparing the composition, comprising the following steps:

[0020] (1) grinding dried seabuckthorn fruit to obtain seabuckthorn fruit powder, mixing the seabuckthorn fruit powder with an ethanol solution, refluxing and extracting for 2 to 4 times, and combining the extracts to obtain a primary extract;

[0021] (2) the primary extract obtained in step (1) is subjected to reduced pressure treatment to recover ethanol to obtain a primary extract;

[0022] (3) vacuum freeze-drying the primary extract obtained in step (2) to obtain seabuckthorn fruit alcohol extract;

[0023] (4) The seabuckthorn fruit ethanol extract obtained in step (3) is mixed with polygonatum, dendrobium, bupleurum, radix trichosanthis, rhizoma phragmites, codonopsis, cornus officinalis, asarum, andrographis paniculata and pericarp of cicada to obtain a composition for treating pulmonary tuberculosis.

[0024] Preferably, the particle size of the crushed fruit in step (1) is 180-220 mesh; the mixing ratio of the seabuckthorn fruit powder and the ethanol solution in step (1) is 80-120 g: 600-900 mL; and the volume fraction of the ethanol solution in step (1) is 55-65%.

[0025] Preferably, the temperature of the reflux extraction in step (1) is 90-100° C., and the time of each reflux extraction is 70-80 min.

[0026] Preferably, the temperature for recovering ethanol by decompression treatment in step (2) is 60-90° C. and the pressure is -0.1 MPa; and the decompression treatment for recovering ethanol is performed until the primary extract is viscous to obtain the primary extract.

[0027] Preferably, the temperature of the vacuum freeze-drying in step (3) is -10 to -30°C, the vacuum degree of the vacuum freeze-drying is 10-3 to 10-4 Pa, and the vacuum freeze-drying is for 36 to 60 hours.

[0028] The present invention also provides application of the composition or the composition prepared by the preparation method in preparing medicine for treating pulmonary tuberculosis.

[0029] The invention also provides a medicine for treating pulmonary tuberculosis, comprising the composition.

[0030] Preferably, the medicine further comprises pharmaceutical excipients.

[0031] Compared with the prior art, the present invention has the following advantages and technical effects:

[0032] The combination of the polygonatum odoratum and the dendrobium can nourish yin and moisten dryness, can enhance the effect of nourishing yin, and is suitable for lung and stomach yin deficiency and liver and kidney yin deficiency; the anti-inflammatory effect of the seabuckthorn fruit alcohol extract can enhance the antipyretic effect of bupleurum, and at the same time, the immune enhancement effect of the seabuckthorn fruit alcohol extract can assist the liver-soothing and depression-relieving and antipyretic effects of bupleurum, and is suitable for enhancing immunity, and the liver-protecting effect of the seabuckthorn fruit alcohol extract can be combined with the liver-soothing and depression-relieving effects of bupleurum, and while treating pulmonary tuberculosis, the liver is protected from toxic damage of drugs; the combination of reed root and trichosanthes has the effects of clearing away heat and detoxifying, can enhance the effect of clearing heat, promote body fluid and quench thirst, and clear heat and promote diuresis; the combination of asarum dispels wind and warms the lungs, andrographis detoxifies and reduces swelling, and pericarp dispels wind and dissipates heat, and codonopsis and cornus officinalis warm the middle and relieve pain, and comprehensively regulates the liver and kidney, so as to achieve the technical effect of rapid effect in treating pulmonary tuberculosis without causing excessive drug burden on the liver and kidney. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0034] Figure 1 It is the average colony count of the test tube slant in the in vitro test against Mycobacterium tuberculosis;

[0035] Figure 2 Statistics on the efficacy of the Chinese medicine treatment group and the Western medicine treatment group;

[0036] Figure 3 Statistics on sputum bacteria negative conversion in the traditional Chinese medicine treatment group and the western medicine treatment group. DETAILED DESCRIPTION

[0037] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0038] It should be understood that the terms described in the present invention are only for describing special embodiments and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper and lower limits of the scope is also specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0039] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0040] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments of the present invention description without departing from the scope or spirit of the present invention. Other embodiments derived from the present invention description will be apparent to the skilled artisan. The present invention description and examples are exemplary only.

[0041] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0042] Unless otherwise specified, the "parts" described in the present invention are all based on mass parts.

[0043] Example 1

[0044] (1) Seabuckthorn dried fruit is crushed to obtain seabuckthorn fruit powder with a particle size of 200 mesh, the seabuckthorn fruit powder is mixed with a 60% ethanol solution in a ratio of 100 g:750 mL, and reflux extraction is performed at 95° C. for 3 times, each time for 75 min, and the extracts are combined to obtain a primary extract;

[0045] (2) treating the primary extract at 75°C and -0.1 MPa under reduced pressure to recover ethanol until the primary extract becomes viscous to obtain the primary extract;

[0046] (3) The initial extract was kept at -20°C and vacuum degree of 10 -4 Pa was vacuum freeze-dried for 48 hours to obtain seabuckthorn fruit alcohol extract;

[0047] (4) 5 parts of seabuckthorn fruit ethanol extract are mixed with 22 parts of polygonatum, 27.5 parts of dendrobium, 9 parts of bupleurum, 25 parts of trichosanthes, 6 parts of phragmites, 16 parts of codonopsis, 7 parts of cornus, 5 parts of asarum, 2.5 parts of andrographis paniculata and 2 parts of cicada shell to obtain a composition for treating pulmonary tuberculosis.

[0048] Example 2

[0049] (1) Seabuckthorn dried fruit is crushed to obtain seabuckthorn fruit powder with a particle size of 180 mesh, the seabuckthorn fruit powder is mixed with 55% ethanol solution in a ratio of 80 g:600 mL, and reflux extraction is performed at 90° C. for 4 times, each time for 70 min, and the extracts are combined to obtain a primary extract;

[0050] (2) the primary extract is treated at 60°C and -0.1 MPa under reduced pressure to recover ethanol until the primary extract becomes viscous to obtain the primary extract;

[0051] (3) The initial extract was kept at -10°C and vacuum degree of 10 -4 Pa vacuum freeze-dried for 60 hours to obtain seabuckthorn fruit alcohol extract;

[0052] (4) 4 parts of seabuckthorn fruit ethanol extract are mixed with 24 parts of polygonatum, 30 parts of dendrobium, 8 parts of bupleurum, 27 parts of trichosanthes, 7 parts of phragmites, 14 parts of codonopsis, 5 parts of cornus, 6 parts of asarum, 2 parts of andrographis and 3 parts of cicada shell to obtain a composition for treating pulmonary tuberculosis.

[0053] Example 3

[0054] (1) Seabuckthorn dried fruit is crushed to obtain seabuckthorn fruit powder with a particle size of 220 mesh, the seabuckthorn fruit powder is mixed with 65% ethanol solution in a ratio of 120 g:900 mL, and reflux extraction is performed at 100° C. for 80 min each time, and the extracts are combined to obtain a primary extract;

[0055] (2) treating the primary extract at 90°C and -0.1 MPa under reduced pressure to recover ethanol until the primary extract becomes viscous to obtain the primary extract;

[0056] (3) The initial extract was kept at -30°C and vacuum degree of 10 -3 Pa vacuum freeze-dried for 36 hours to obtain seabuckthorn fruit alcohol extract;

[0057] (4) 6 parts of seabuckthorn fruit ethanol extract are mixed with 20 parts of polygonatum, 15 parts of dendrobium, 10 parts of bupleurum, 23 parts of trichosanthes, 5 parts of phragmites, 18 parts of codonopsis, 9 parts of cornus, 4 parts of asarum, 3 parts of andrographis and 1 part of cicada shell to obtain a composition for treating pulmonary tuberculosis.

[0058] Example 4

[0059] (1) Seabuckthorn dried fruit is crushed to obtain seabuckthorn fruit powder with a particle size of 200 mesh, the seabuckthorn fruit powder is mixed with 60% ethanol solution in a ratio of 100 g:900 mL, and reflux extraction is performed at 95° C. for 3 times, each time for 70 min, and the extracts are combined to obtain a primary extract;

[0060] (2) the primary extract is treated at 80°C and -0.1 MPa under reduced pressure to recover ethanol until the primary extract becomes viscous to obtain the primary extract;

[0061] (3) The initial extract was kept at -25°C and vacuum degree of 10 -4 Pa vacuum freeze-dried for 50 h to obtain seabuckthorn fruit alcohol extract;

[0062] (4) 5.5 parts of seabuckthorn fruit ethanol extract are mixed with 21 parts of polygonatum, 20 parts of dendrobium, 9.5 parts of bupleurum, 24 parts of trichosanthes, 5.5 parts of phragmites australis, 17 parts of codonopsis pilosula, 8 parts of cornus officinalis, 4.5 parts of asarum, 2.5 parts of andrographis paniculata and 2.5 parts of cicada shell to obtain a composition for treating pulmonary tuberculosis.

[0063] Example 5

[0064] (1) Crush the dried seabuckthorn fruit to obtain seabuckthorn fruit powder with a particle size of 200 mesh, mix the seabuckthorn fruit powder with a volume fraction of 55% ethanol solution in a ratio of 100 g: 800 mL, extract under reflux at 95° C. for 3 times, each time for 80 min, and combine the extracts to obtain a primary extract;

[0065] (2) the primary extract is treated at 70°C and -0.1 MPa under reduced pressure to recover ethanol until the primary extract becomes viscous to obtain the primary extract;

[0066] (3) The initial extract was kept at -15°C and vacuum degree of 10 -4 Pa vacuum freeze-dried for 55 h to obtain seabuckthorn fruit alcohol extract;

[0067] (4) 4.5 parts of seabuckthorn fruit ethanol extract are mixed with 23 parts of polygonatum, 25 parts of dendrobium, 8.5 parts of bupleurum, 26 parts of trichosanthes, 6.5 parts of phragmites, 15 parts of codonopsis, 6 parts of cornus, 5.5 parts of asarum, 2.5 parts of andrographis paniculata and 1.5 parts of cicada shell to obtain a composition for treating pulmonary tuberculosis.

[0068] Comparative Example 1

[0069] (1) Seabuckthorn dried fruit is crushed to obtain seabuckthorn fruit powder with a particle size of 200 mesh, the seabuckthorn fruit powder is mixed with a 60% ethanol solution in a ratio of 100 g:750 mL, and reflux extraction is performed at 95° C. for 3 times, each time for 75 min, and the extracts are combined to obtain a primary extract;

[0070] (2) treating the primary extract at 75°C and -0.1 MPa under reduced pressure to recover ethanol until the primary extract becomes viscous to obtain the primary extract;

[0071] (3) The initial extract was kept at -20°C and vacuum degree of 10 -4 Pa was vacuum freeze-dried for 48 hours to obtain seabuckthorn fruit alcohol extract;

[0072] (4) 5 parts of seabuckthorn fruit ethanol extract are mixed with 22 parts of polygonatum, 27.5 parts of dendrobium, 9 parts of astragalus, 25 parts of trichosanthes, 6 parts of phragmites, 16 parts of codonopsis, 7 parts of cornus, 5 parts of asarum, 2.5 parts of andrographis paniculata and 2 parts of cicada shell to obtain a composition for treating pulmonary tuberculosis.

[0073] Astragalus: It has the effects of raising yang and lifting sunken, strengthening the body's defense system, promoting urination, and removing toxins and promoting tissue regeneration. It is mainly used to treat spleen qi deficiency syndrome, lung qi deficiency syndrome, spontaneous sweating syndrome due to qi deficiency, qi and blood deficiency, sores that are difficult to heal or ulcers that are difficult to heal for a long time, etc.

[0074] Comparative Example 2

[0075] (1) Seabuckthorn dried fruit is crushed to obtain seabuckthorn fruit powder with a particle size of 200 mesh, the seabuckthorn fruit powder is mixed with a 60% ethanol solution in a ratio of 100 g:750 mL, and reflux extraction is performed at 95° C. for 3 times, each time for 75 min, and the extracts are combined to obtain a primary extract;

[0076] (2) treating the primary extract at 75°C and -0.1 MPa under reduced pressure to recover ethanol until the primary extract becomes viscous to obtain the primary extract;

[0077] (3) The initial extract was kept at -20°C and vacuum degree of 10 -4 Pa was vacuum freeze-dried for 48 hours to obtain seabuckthorn fruit alcohol extract;

[0078] (4) 5 parts of seabuckthorn fruit ethanol extract are mixed with 22 parts of polygonatum odoratum, 27.5 parts of adenophora australis, 9 parts of bupleurum, 25 parts of trichosanthes, 6 parts of phragmites australis, 16 parts of codonopsis pilosula, 7 parts of cornus officinalis, 5 parts of asarum, 2.5 parts of andrographis paniculata and 2 parts of cicada shell to obtain a composition for treating pulmonary tuberculosis.

[0079] Adenophora australis: nourishes yin and clears the lungs, benefits the stomach and produces fluid, resolves phlegm, and invigorates qi. It is used for lung heat and dry cough, yin deficiency and fatigue cough, dry cough and sticky phlegm, insufficient stomach yin, poor appetite and vomiting, insufficient qi and yin, and irritability and dry mouth.

[0080] Comparative Example 3

[0081] (1) Seabuckthorn dried fruit is crushed to obtain seabuckthorn fruit powder with a particle size of 200 mesh, the seabuckthorn fruit powder is mixed with water in a ratio of 100 g:750 mL, and reflux extraction is performed at 95° C. for 3 times, each time for 75 min, and the extracts are combined to obtain a primary extract;

[0082] (2) treating the primary extract at 75°C and -0.1 MPa pressure reduction until the primary extract becomes viscous to obtain the primary extract;

[0083] (3) The initial extract was kept at -20°C and vacuum degree of 10-4 Pa was vacuum freeze-dried for 48 h to obtain the seabuckthorn fruit water extract;

[0084] (4) 5 parts of seabuckthorn fruit water extract are mixed with 22 parts of polygonatum, 27.5 parts of dendrobium, 9 parts of bupleurum, 25 parts of trichosanthes, 6 parts of phragmites, 16 parts of codonopsis, 7 parts of cornus, 5 parts of asarum, 2.5 parts of andrographis paniculata and 2 parts of cicada shell to obtain a composition for treating pulmonary tuberculosis.

[0085] Experimental example

[0086] 1. In vitro test against Mycobacterium tuberculosis

[0087] Drug-based method: Modified Roche medium is mixed with distilled water and glycerol in the ratio of 40.84 g: 600 mL: 12 mL, and boiled at 100°C for 10 min. High temperature sterilization is carried out at 121°C for 20 min. After cooling to room temperature, it is mixed with 1000 mL of sterile whole egg liquid and divided into 10 mL portions for later use.

[0088] The compositions prepared in Examples 1 to 5 and Comparative Examples 1 to 3 were added with water at a ratio of 1 g: 10 mL, boiled for 6 hours, filtered, and the filtrate was taken. The filtrate was mixed with the culture medium at a volume ratio of 1:10 to obtain Example 1 Group, Example 2 Group, Example 3 Group, Example 4 Group, Example 5 Group, Comparative Example 1 Group, Comparative Example 2 Group, and Comparative Example 3 Group, which were set aside. The culture medium with an isoniazid content of 1 μg / mL was used as the positive control group, and the negative control group was a drug-free culture medium.

[0089] Each culture medium was placed on a slant, heated with flowing steam at 85°C for 50 min, and then cooled for use. A suspension of Mycobacterium tuberculosis H37Rv (10 8 CFU / mL) and then placed in a 36.5℃ constant temperature incubator for 15 days. Each group was repeated three times. After the incubation, the number of colonies on the slant of the test tube was less than 5 (including 5) and was considered valid.

[0090] Table 1 Results of in vitro tests against Mycobacterium tuberculosis

[0091]

[0092]

[0093] Note: Valid is “+”, invalid is “-”.

[0094] The results are shown in Table 1 and Figure 1As shown in the results of the in vitro test against Mycobacterium tuberculosis, the compositions prepared by the present invention have effective resistance to Mycobacterium tuberculosis. After replacing Bupleurum in Example 1 with Astragalus, the composition of Comparative Example 1 still has effective resistance to Mycobacterium tuberculosis, but the resistance is significantly reduced; when Dendrobium in Example 1 is replaced with Adenophora australis with similar efficacy, the compatibility efficacy of the composition is greatly affected, and the resistance to Mycobacterium tuberculosis is ineffective. After changing the Hippophae rhamnoides fruit extract to an aqueous extract, the resistance to Mycobacterium tuberculosis is significantly reduced.

[0095] 2. Experiment on the influence of immune indicators on mouse tuberculosis model

[0096] Primary Kunming mice (female, 18-22 g) were fixed and 0.2 mL / mouse of a 1 mg / mL Mycobacterium tuberculosis H37Rv bacterial suspension was injected into the tail vein. After injection, the puncture site was compressed to stop bleeding for 1 min.

[0097] After 1 day of observation after modeling, mice meeting the requirements were randomly divided into 10 groups: Example 1 group, Example 2 group, Example 3 group, Example 4 group, Example 5 group, Comparative Example 1 group, Comparative Example 2 group, Comparative Example 3 group, model group and rifampicin group (first dissolved with one drop of dimethylformamide and then diluted with distilled water to 1 g / mL), with 12 mice in each group. Water and diet were free.

[0098] The drug was administered on the second day after modeling. The model group was gavaged with 0.2 mL / 10 mg of normal saline per day; the rifampicin group was gavaged with 0.2 mL / 10 mg per day; the Example 1-5 groups and the Comparative Example 1-3 groups were respectively added with water at a ratio of 1 g: 10 mL, boiled for 6 hours, filtered, and the filtrate was taken at 0.2 mL / 10 mg per day; and the gavage was continued for 28 days.

[0099] The mice in each group were weighed after the last administration. After the weight measurement, the eyeballs were removed in a conscious state to collect blood, which was placed in a heparin anticoagulated EP tube. The thymus, spleen, liver, and lung were separated. The immunohistochemical method was used to measure T cell subsets, and the specific operation was carried out according to the instructions of the mouse T lymphocyte subset ELISA kit (Shanghai Huabang Biotechnology Co., Ltd.); the ELISA method was used to detect the levels of mouse plasma IFN-r and IgG in strict accordance with the instructions of the IFN-γ kit (ADL ELISA Company, USA) and the IgG kit (ADLELISA Company, USA).

[0100] The measurement data were expressed as x±s. The differences among the groups were analyzed using t test.

[0101] Table 2 T lymphocyte subsets of mice in each group

[0102] Group Number of individuals <![CDATA[CD 4+ ]]> <![CDATA[CD 8+ ]]> <![CDATA[CD 4+ / CD 8+ ]]> Example 1 Group 12 35.13±2.14** 15.46±2.01 2.27±0.24** Example 2 Group 12 34.69±2.31** 16.27±2.47 2.13±0.22** Example 3 Group 12 32.63±2.09** 15.78±2.09 2.07±0.22* Example 4 Group 12 33.19±2.25** 15.07±2.06 2.20±0.27** Example 5 Group 12 30.79±2.06** 15.17±2.11 2.03±0.21* Comparative Example 1 12 25.19±2.14* 14.38±2.36 1.75±0.31* Comparative Example 2 12 22.71±1.83* 15.72±2.27 1.44±0.28 Comparative Example 3 12 20.49±1.82* 15.58±2.24 1.32±0.27 Model Group 12 14.67±1.23 15.12±1.87 0.97±0.12 Rifampicin group 12 27.14±2.55** 15.34±1.56 1.77±0.18*

[0103] Note: Compared with the model group, ** represents P < 0.01, * represents P < 0.05.

[0104] Table 3 Serum IFN-γ and IgG in each group of mice

[0105] Group Number of individuals IFN-γ (pg / mL) IgG(g / L) Example 1 Group 10 99.43±2.01** 13.55±1.15** Example 2 Group 10 96.78±2.07** 12.69±1.54** Example 3 Group 10 95.19±2.64** 12.05±1.11** Example 4 Group 10 94.92±2.39** 11.07±1.28** Example 5 Group 10 95.05±2.09** 10.87±1.44** Comparative Example 1 10 91.94±2.22* 9.73±1.76* Comparative Example 2 10 90.01±2.61* 9.56±1.32* Comparative Example 3 10 88.31±2.29* 8.03±1.56 Model Group 10 59.12±1.66 7.18±1.74 Rifampicin group 10 90.15±2.09* 9.38±1.82*

[0106] Note: Compared with the model group, ** represents P < 0.01, * represents P < 0.05.

[0107] After being infected with tuberculosis bacteria, the immune system will regulate the body through its complex balance system to make immunity. The immune state is a dynamic process. As shown in Table 2 and Table 3 above, the compositions prepared in Examples 1 to 5 of the present invention significantly improved the CD4 + Subgroup ratio and CD 4+ / CD 8+ ratio, significantly increased the CD 4+ The number of T cells was increased, and the levels of IFN-γ and IgG were significantly increased.

[0108] 3. Clinical Application

[0109] From March 2020 to March 2023, 108 cases of pulmonary tuberculosis were confirmed in the First Affiliated Hospital of Shihezi University and were randomly divided into two groups, with 54 cases in each group, a Chinese medicine treatment group (using the composition of Example 1, 1 dose per day, decocted in water twice, taken twice a day, morning and evening), and a Western medicine treatment group (using Western medicine, 3 times a day, each time 0.3g of remifentanil, 0.45g of rifampicin, 0.75g of ethambutol), with 30 days as one course of treatment.

[0110] After the treatment begins, record the improvement of the patient's symptoms and signs and whether there are any adverse reactions. The improvement of symptoms and signs can be detected by X-ray and CT examinations. Take a chest X-ray once before treatment and once every 15 days thereafter.

[0111] Every 10 days of treatment, sputum smear was checked for Mycobacterium tuberculosis once in parallel in the three groups, and liver function, blood routine and erythrocyte sedimentation rate were checked once each.

[0112] Judgment criteria: Cured: the signs of lung lesions disappear, the results of 3 parallel groups of sputum smears are all negative, and the pulmonary tuberculosis lesions are completely absorbed; effective: the signs of lung lesions disappear, the results of 3 parallel groups of sputum smears are all negative, and the pulmonary tuberculosis lesions are absorbed by 40% to 60%; ineffective: the signs of lung lesions disappear, the results of 3 parallel groups of sputum smears are positive, and the absorption of pulmonary tuberculosis lesions is ≤40%.

[0113] Table 4 Efficacy results

[0114] Group Total number of people cure efficient invalid Total effective rate (%) Chinese medicine treatment group 54 46 6 2 96.30％ Western medicine treatment group 54 22 21 11 79.63％

[0115] According to Table 4 and Figure 2 According to the records, the total effective rate of the Chinese medicine treatment group was significantly improved, and the effect was fast, and the number of patients cured within 1 month increased significantly.

[0116] Table 5 Sputum bacteria negative conversion

[0117] Group Sputum bacteria negative conversion rate on the 20th day (percentage) Sputum bacteria negative conversion rate on the 30th day (percentage) Chinese medicine treatment group 8(14.81％) 52(96.30％) Western medicine treatment group 10(18.52％) 43(79.63％)

[0118] The negative conversion of sputum bacteria recorded in Table 5 means that the sputum smears of the three groups in parallel are all negative. Figure 3 According to the records, the sputum bacteria-negative conversion rate of the Chinese medicine treatment group on the 20th day was slightly lower than that of the Western medicine treatment group. After continuous medication for 30 days, the therapeutic effect was significantly better than that of conventional Western medicine treatment.

[0119] The embodiments described above are only descriptions of the preferred modes of the present invention, and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by ordinary technicians in this field should all fall within the protection scope determined by the claims of the present invention.

Claims

1. A composition for treating pulmonary tuberculosis, characterized in that: It includes the following components by weight: 20-24 parts of Polygonatum odoratum, 15-30 parts of Dendrobium officinale, 4-6 parts of seabuckthorn fruit alcohol extract, 8-10 parts of Bupleurum chinense, 23-27 parts of Radix Trichosanthis, 5-7 parts of Phragmites australis, 14-18 parts of Codonopsis pilosula, 5-9 parts of Cornus officinalis, 4-6 parts of Asarum, 2-3 parts of Andrographis paniculata, and 1-3 parts of Periostracum Cicadae.

2. The composition according to claim 1, characterized in that The seabuckthorn fruit alcohol extract is obtained by extracting seabuckthorn dried fruit with an ethanol solution.

3. The method for preparing the composition according to claim 1 or 2, characterized in that: The following steps are involved: (1) grinding dried seabuckthorn fruit to obtain seabuckthorn fruit powder, mixing the seabuckthorn fruit powder with an ethanol solution, refluxing and extracting for 2 to 4 times, and combining the extracts to obtain a primary extract; (2) the primary extract obtained in step (1) is subjected to reduced pressure treatment to recover ethanol to obtain a primary extract; (3) vacuum freeze-drying the primary extract obtained in step (2) to obtain seabuckthorn fruit alcohol extract; (4) The seabuckthorn fruit ethanol extract obtained in step (3) is mixed with polygonatum, dendrobium, bupleurum, radix trichosanthis, rhizoma phragmites, codonopsis, cornus officinalis, asarum, andrographis paniculata and pericarp of cicada to obtain a composition for treating pulmonary tuberculosis.

4. The preparation method according to claim 3, characterized in that: The particle size of the crushed fruit in step (1) is 180-220 meshes, the mixing ratio of the seabuckthorn fruit powder and the ethanol solution in step (1) is 80-120 g: 600-900 mL; and the volume fraction of the ethanol solution in step (1) is 55-65%.

5. The preparation method according to claim 3, characterized in that: The temperature of the reflux extraction in step (1) is 90-100° C., and the time of each reflux extraction is 70-80 minutes.

6. The preparation method according to claim 3, characterized in that: The temperature for recovering ethanol by decompression treatment in step (2) is 60-90° C. and the pressure is -0.1 MPa; the decompression treatment is performed to recover ethanol until the initial extract is in a viscous state to obtain the initial extract.

7. The preparation method according to claim 3, characterized in that: The temperature of the vacuum freeze drying in step (3) is -10 to -30°C, and the vacuum degree of the vacuum freeze drying is 10 -3 ~10 -4 Pa, the vacuum freeze-drying is 36 to 60 hours.

8. Use of the composition according to claim 1 or 2 or the composition prepared by the preparation method according to any one of claims 3 to 7 in preparing drugs for treating pulmonary tuberculosis.

9. A drug for treating pulmonary tuberculosis, characterized in that: The invention comprises the composition according to claim 1 or 2.

10. The drug according to claim 9, characterized in that: The medicine also includes pharmaceutical excipients.

Images