Application of probiotic composition in preparation of medicine for preventing and / or treating pneumonia

Abstract

The invention provides application of a probiotic composition in preparation of a medicine for preventing and / or treating pneumonia, and belongs to the technical field of biological medicine. The probiotic composition comprises sophora flower bud powder, a broccoli seed aqueous extract, lactobacillus rhamnosus and bifidobacterium animalis subsp. Lactis. Research finds that the probiotic composition can significantly relieve pulmonary edema caused by pneumonia and also can significantly reduce the level of inflammatory factors in pneumonia, so that the probiotic composition has the effect of preventing and / or treating pneumonia, and more choices are provided for clinical drugs for preventing and / or treating pneumonia.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and in particular relates to the use of a probiotic composition in preparing a medicine for preventing and / or treating pneumonia. Background Art

[0002] Pneumonia refers to inflammation of the terminal airways, alveoli, and interstitial lung tissue. It can be caused by pathogenic microorganisms, immune damage, physical and chemical factors, allergies, and medications. The main clinical symptoms are fever, cough, and sputum production. Some cases can develop severe pneumonia, leading to circulatory and respiratory failure, which is life-threatening. Bacterial pneumonia is the most common pneumonia and one of the most common infectious diseases. In recent years, despite the continuous development and clinical application of powerful antimicrobial drugs, the mortality rate of pneumonia has not decreased significantly but has increased. Currently, its morbidity, mortality, and disease burden remain at high levels. Currently, pneumonia still has a high morbidity and mortality rate in the elderly, the young, and the immunocompromised, placing a heavy disease burden on society and families.

[0003] Pneumonia is a serious respiratory infection. Currently, treatments for pneumonia mainly include antiviral drugs and hormones, but the effectiveness of treatment varies depending on the pathogen. There are not many treatments for pneumonia. For example, for pneumonia caused by the influenza virus, treatment options are very limited. Patients are usually given oxygen to maintain lung oxygenation, and ultimately recovery relies on the patient's own production of influenza antibodies. Furthermore, there are currently only antiviral drugs for influenza A virus. While these drugs can prevent the virus from entering cells, they are ineffective against viruses that have already entered cells. Therefore, more research is needed to explore new treatment options and drugs for the treatment of pneumonia.

[0004] Broccoli seed extract is rich in glucoraphanin, which can be converted to sulforaphane by myrosinase or intestinal microbes. This sulforaphane activates the expression of the transcription factor NRF2, producing antioxidant effects. Sophora japonica flour is rich in quercetin, a flavonol. Numerous in vitro and in vivo studies have shown that it plays a role in various tumor diseases by regulating biological processes such as oxidative stress and apoptosis. Lactobacillus rhamnosus GG, a third-generation probiotic, is a safe and effective strain for promoting digestive health and maintaining immune function. Bifidobacterium lactis HN019 is a strain isolated from yogurt. However, the combined use of broccoli seed extract, Sophora japonica flour, Lactobacillus rhamnosus, and Bifidobacterium animalis subsp. lactis for the prevention and / or treatment of pneumonia has not been reported. Summary of the Invention

[0005] In view of this, an object of the present invention is to provide a use of a probiotic composition in the preparation of a medicament for preventing and / or treating pneumonia.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] The present invention provides an application of a probiotic composition in preparing a medicine for preventing and / or treating pneumonia. The probiotic composition comprises sophora japonica rice flour, broccoli seed water extract, Lactobacillus rhamnosus and Bifidobacterium animalis subsp. lactis.

[0008] Preferably, the Lactobacillus rhamnosus is Lactobacillus rhamnosus GG; and the Bifidobacterium animalis subsp. lactis is Bifidobacterium animalis subsp. lactis HN019.

[0009] Preferably, the pneumonia is lipopolysaccharide-induced pneumonia.

[0010] Preferably, the probiotic composition significantly reduces pulmonary edema.

[0011] Preferably, the probiotic composition significantly reduces the expression level of inflammatory factors.

[0012] Preferably, the inflammatory factors include one or more of IL-6, IL-1β and TNF-α.

[0013] Preferably, the mass ratio of the sophora japonica flour and the broccoli seed water extract is 1:1; the effective viable count ratio of the rhamnosus lactobacillus and the animal Bifidobacterium lactis subspecies is (18-22):3; the effective viable count ratio of the sophora japonica flour and the rhamnosus lactobacillus is 1 mg: 5.5-6.5 billion cfu.

[0014] Preferably, the drug comprises pharmaceutically acceptable excipients.

[0015] Preferably, the probiotic composition is the only active ingredient of the medicine.

[0016] The present invention provides a medicine for preventing and / or treating pneumonia, which comprises a pharmaceutically acceptable excipient and the above-mentioned probiotic composition.

[0017] Compared with the prior art, the present invention has the following beneficial effects:

[0018] The present invention provides a use of a probiotic composition in the preparation of a drug for preventing and / or treating pneumonia. Studies have found that the probiotic composition of the present invention can significantly alleviate pulmonary edema caused by pneumonia and can also significantly reduce the levels of inflammatory factors in pneumonia. Therefore, the probiotic composition has the effect of preventing and / or treating pneumonia. The present invention provides a new option for clinically preventing and / or treating pneumonia drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 H&E staining of mouse lung tissues after treatment in different groups;

[0020] Figure 2 This is a comparison chart of the expression levels of pneumonia inflammatory factors IL-6, IL-1β and TNF-α in the serum of mice after treatment in different groups. DETAILED DESCRIPTION

[0021] The present invention provides an application of a probiotic composition in preparing a medicine for preventing and / or treating pneumonia. The probiotic composition comprises sophora japonica rice flour, broccoli seed water extract, Lactobacillus rhamnosus and Bifidobacterium animalis subsp. lactis.

[0022] In the present invention, as a preferred embodiment, the probiotic composition comprises sophora japonica flour, broccoli seed aqueous extract, Lactobacillus rhamnosus, and Bifidobacterium animalis subsp. lactis. The Lactobacillus rhamnosus is preferably Lactobacillus rhamnosus GG; and the Bifidobacterium animalis subsp. lactis is preferably Bifidobacterium animalis subsp. lactis HN019. The sources of the sophora japonica flour, broccoli seed aqueous extract, Lactobacillus rhamnosus GG, and Bifidobacterium animalis subsp. lactis HN019 are not particularly limited; commercially available products in the art may be used.

[0023] In the present invention, the pneumonia is lipopolysaccharide-induced pneumonia. The method for preparing the pneumonia model mice comprises administering a single intranasal instillation of 5 mg / kg lipopolysaccharide to each mouse for 12 hours to obtain the pneumonia model mice.

[0024] In the present invention, the mass ratio of the sophora japonica flour and the broccoli seed water extract is 1:1; the mass effective viable count ratio of the rhamnosus lactobacillus and the animal Bifidobacterium lactis subspecies is preferably (18-22):3, further preferably (19-21):3, and more preferably 20:3; the mass effective viable count ratio of the sophora japonica flour and the rhamnosus lactobacillus is preferably 1 mg:5.5-6.5 billion cfu, further preferably 1 mg:5.7-6.3 billion cfu, and more preferably 1 mg:6 billion cfu. The probiotic composition of the present invention using the above content or effective viable count can not only significantly reduce pulmonary edema, but also significantly reduce the expression level of inflammatory factors. The pulmonary edema is pulmonary edema caused by pneumonia. The inflammatory factors are inflammatory factors caused by pneumonia, and the inflammatory factors preferably include one or more of IL-6, IL-1β and TNF-α.

[0025] The present invention provides a medicine for preventing and / or treating pneumonia, which comprises a pharmaceutically acceptable excipient and the above-mentioned probiotic composition.

[0026] In the present invention, the sophora japonica flour, broccoli seed aqueous extract, Lactobacillus rhamnosus, and Bifidobacterium animalis lactis subsp. lactis in the probiotic composition can be administered separately or mixed according to dosage and then administered together. The administration method includes oral administration.

[0027] In the present invention, the drug comprises pharmaceutically acceptable excipients. The excipients include one or more of a solvent, a flavoring agent, an excipient, an antioxidant, and a preservative. The mass ratio of the probiotic composition to the drug is 50% to 90%. The probiotic composition of the present invention can be prepared by conventional methods into any conventional formulation, such as granules, tablets, lyophilized formulations, capsules, syrups, or solutions.

[0028] In the present invention, the drug can be used as the sole active ingredient of the probiotic composition for the prevention and / or treatment of pneumonia, or it can be combined with other active drugs for the prevention and / or treatment of pneumonia to achieve the purpose of treating pneumonia. The probiotic composition is preferably the sole active ingredient of the drug. When the probiotic composition of the present invention prevents and / or treats pneumonia, the effective dosage range of the sophora japonica powder and the broccoli seed water extract is 4 to 7 mg / kg / d, the effective viable count of the rhamnosus Lactobacillus is 60 billion cfu / kg / d, and the effective viable count of the animal Bifidobacterium lactis subspecies is 9 billion cfu / kg / d. The effective dose or effective viable count in the present invention refers to the amount of the therapeutic agent to treat, alleviate or prevent the target disease or condition.

[0029] In the present invention, unless otherwise specified, all raw material components are commercially available products well known to those skilled in the art.

[0030] The technical solutions provided by the present invention are described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0031] In the following examples, Lactobacillus rhamnosus GG was purchased from Qingdao Miaopinyuan International Trade Co., Ltd., product number: G003170, with a specification of 300 billion cfu / g.

[0032] Bifidobacterium animalis subsp. lactis HN019 was purchased from Fonterra Cooperative Group Limited with product number 61018295 and a specification of 300 billion cfu / g.

[0033] Sophora japonica rice powder was purchased from Indina Biotechnology (Shanghai) Co., Ltd., product number: 9047510A01.

[0034] Broccoli seed aqueous extract was purchased from Ganzhou Huahan Biotechnology Co., Ltd., product number: 60202007.

[0035] MRS medium: 10 g / L tryptone, 5 g / L yeast extract, 10 g / L beef extract, 20 g / L glucose, 5 g / L sodium acetate, 2 g / L ammonium dihydrogen citrate, 1 ml / L Tween 80, 0.58 g / L magnesium sulfate, 0.25 g / L manganese sulfate, adjust the pH to about 6.2, and sterilize at 115°C.

[0036] Example 1

[0037] (1) Medicaments and their preparation

[0038] S1. A probiotic composition for treating pneumonia, comprising the following components:

[0039] Sophora japonica rice flour, broccoli seed aqueous extract, Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis HN019.

[0040] Wherein, the sophora japonica rice flour and the broccoli seed water extract were respectively prepared with physiological saline to obtain a 1 mg / mL sophora japonica rice flour solution and a 1 mg / mL broccoli seed water extract solution.

[0041] Lactobacillus rhamnosus GG: Lactobacillus rhamnosus GG was cultured in MRS medium at 37° C. for 20 hours, centrifuged at 7000 rpm for 30 minutes, and the precipitate was collected to obtain Lactobacillus rhamnosus GG.

[0042] Bifidobacterium animalis subsp. lactis HN019: Bifidobacterium animalis subsp. lactis HN019 was cultured in MRS medium at 37° C. for 20 hours, centrifuged at 7000 rpm for 30 minutes, and the precipitate was collected to obtain Bifidobacterium animalis subsp. lactis HN019.

[0043] S2. Dexamethasone solution: prepare a dexamethasone solution with a final concentration of 500 μg / mL using normal saline.

[0044] S3. Preparation of lipopolysaccharide (LPS) solution: prepare a lipopolysaccharide solution with a final concentration of 2 mg / mL using physiological saline.

[0045] (2) Experimental grouping and drug administration

[0046] C57BL / 6 mice (female, 4 weeks old, 18-22 g) were divided into four groups, with 8 mice in each group, namely, blank group (Vehicle), model group (LPS), LPS+dexamethasone group (LPS+Dexa), and LPS+probiotic composition group (LPS+Combined).

[0047] Among them, the blank group and the model group were gavaged with normal saline once a day for 3 consecutive days; the LPS + dexamethasone group was gavaged with the above-mentioned dexamethasone solution at a dose of 5 mg / kg once a day for 3 consecutive days; the LPS + probiotic composition group was gavaged with the above-mentioned sophora japonica powder solution at a dose of 10 mg / kg, the above-mentioned broccoli seed aqueous extract solution at a dose of 10 mg / kg, the above-mentioned rhamnosus Lactobacillus GG at a dose of 60 billion cfu / kg and the above-mentioned probiotic composition solution at a dose of 9 billion cfu / kg for each C57BL / 6 mouse. u / kg of the probiotic composition obtained by mixing the above-mentioned animal Bifidobacterium lactis subsp. HN019 was gavaged once a day for 3 consecutive days; 1 hour after the last administration, except for the blank group, each mouse in the model group, LPS + dexamethasone group and LPS + probiotic composition group was treated with a one-time intranasal instillation of 5 mg / kg of the above-mentioned LPS solution for 12 hours, and the pathological changes in lung tissue and inflammation-related molecular indicators (IL-6, IL-1β, TNF-α) of mice in each group were detected to verify whether the pneumonia model was successfully established and the effect of drug intervention on pneumonia.

[0048] Lung tissue samples were taken from mice in each group and the pathological changes of the lungs were observed by H&E staining.

[0049] Figure 1 The results showed that compared with the blank control group, the model group mice had significant pulmonary edema in their lung tissue, indicating that the pneumonia mouse model was successfully established. In the LPS-induced pneumonia mouse model, administration of dexamethasone (positive control drug) and the probiotic composition significantly alleviated the pneumonia-induced pulmonary edema, demonstrating that the probiotic composition of the present invention can alleviate pneumonia symptoms.

[0050] Blood was collected from the eyeballs of mice in each group and centrifuged at 4500 rpm for 15 min. The upper serum was collected and the levels of interleukin 6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor α (TNF-α) in the serum were detected by enzyme-linked immunosorbent assay (ELISA).

[0051] Figure 2 The results showed that compared with the blank control group, LPS treatment in the model group significantly induced the expression of inflammatory factors IL-6, IL-1β, and TNF-α, further indicating that the LPS-induced pneumonia mouse model was successfully constructed. In addition, in the LPS-induced pneumonia mouse model, dexamethasone (positive control drug) and the probiotic composition were respectively administered to significantly inhibit the expression of IL-6, IL-1β, and TNF-α. It is worth noting that the inhibitory effect of the probiotic composition of the present invention on pneumonia inflammatory factors is significantly stronger than that of the positive control drug dexamethasone. The probiotic composition can significantly treat pneumonia and is superior to the positive control drug dexamethasone.

[0052] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. Use of a probiotic composition in preparing a medicament for preventing and / or treating pneumonia, characterized in that: The probiotic composition comprises sophora japonica rice flour, broccoli seed water extract, Lactobacillus rhamnosus and Bifidobacterium animalis subsp. lactis.

2. The use according to claim 1, characterized in that The Lactobacillus rhamnosus is Lactobacillus rhamnosus GG; the Bifidobacterium animalis subspecies lactis is Bifidobacterium animalis subspecies lactis HN019.

3. The use according to claim 1, characterized in that The pneumonia is lipopolysaccharide-induced pneumonia.

4. The use according to claim 1, characterized in that The probiotic composition significantly reduces pulmonary edema.

5. The use according to claim 1, characterized in that The probiotic composition significantly reduces the expression level of inflammatory factors.

6. The use according to claim 5, characterized in that The inflammatory factors include one or more of IL-6, IL-1β and TNF-α.

7. The use according to claim 1, characterized in that The mass ratio of the sophora japonica flour and the broccoli seed water extract is 1:1; the effective viable bacterial count ratio of rhamnosus lactobacillus and animal bifidobacterium lactis is (18-22):3; the effective viable bacterial count ratio of the sophora japonica flour and rhamnosus lactobacillus is 1 mg: 5.5-6.5 billion cfu.

8. The use according to claim 1, characterized in that The drug includes pharmaceutically acceptable excipients.

9. The use according to claim 1, characterized in that The probiotic composition is the only active ingredient of the medicine.

10. A drug for preventing and / or treating pneumonia, characterized in that: The medicine comprises pharmaceutically acceptable excipients and the probiotic composition according to any one of claims 1 to 9.

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