阅读说明：本技术 用于预防或治疗呼吸道炎症的包含荔枝草和红参的组合草药提取物作为活性成分的组合物及其用途 (Composition for preventing or treating respiratory inflammation comprising combined herb extracts of Salvia plebeia and Red Ginseng as active ingredients and use thereof ) 是由 愼汉縡 金孝根 李文镛 郭孝民 闵惠正 金荣信 韩昌均 庆钟秀 印敎 金种汉 金 于 2018-05-10 设计创作，主要内容包括：本发明涉及用于预防和治疗呼吸道炎症疾病的使用混合的草药混合物的组合物和健康功能食品。通过如下各种实验已证实本发明的组合提取物显示出比各个草药提取物更有效的对呼吸道炎症疾病的抑制作用：例如BAL(支气管肺泡灌洗液)的细胞数的确定(实验实施例1)；BAL液内的白细胞中的CD11b+/Gr-1+比的确定(实验实施例2)；肺组织中的炎性细胞因子的RNA表达水平的确定(实验实施例3)；BALF中的炎性细胞因子的RNA表达水平的确定(实验实施例4)；肺组织学(实验实施例5)；简要临床测试(实验实施例7)等。因此,可将本发明所述的草药提取物在用于预防和治疗呼吸道炎症疾病的药物组合物、健康功能食品和健康补充食品中有效地使用。(The present invention relates to a composition and a health functional food for preventing and treating respiratory inflammation diseases using a mixed herbal mixture. The combined extracts of the present invention have been confirmed to show more effective inhibition of respiratory inflammatory diseases than the respective herbal extracts by the following various experiments: determination of the number of cells of, for example, BAL (bronchoalveolar lavage) (experimental example 1); determination of the CD11b +/Gr-1+ ratio in leukocytes in BAL fluid (Experimental example 2); determination of RNA expression level of inflammatory cytokines in lung tissue (experimental example 3); determination of RNA expression levels of inflammatory cytokines in BALF (experimental example 4); lung histology (experimental example 5); brief clinical tests (Experimental example 7), and the like. Therefore, the herbal extract according to the present invention can be effectively used in pharmaceutical compositions, health functional foods and health supplement foods for preventing and treating respiratory inflammatory diseases.)

1. A pharmaceutical composition for preventing and treating respiratory inflammation diseases, comprising a combined herbal extract of Salvia plebeia and Red Ginseng as an active ingredient.

2. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises a combined herbal extract of common sage and red ginseng having a mixing ratio (w/w) based on the dry weight of each extract as follows: 0.01-100:100-0.01 (w/w).

3. The pharmaceutical composition of claim 1, wherein the extract is soluble in distilled water, C₁-C₄An alcohol or a mixture thereof.

4. The pharmaceutical composition of claim 1, wherein the common sage or red ginseng is the whole plant, root, stem or flower of the common sage or red ginseng used as a basic extraction material.

5. The pharmaceutical composition of claim 1, wherein the red ginseng is a processed ginseng having 2-10 years of rooting selected from the group consisting of: radix seu folium Gynurae Yunnanensis, radix Panacis Quinquefolii, Notoginseng radix, Vietnamese Ginseng radix, Panax elegator, Gynura macrophylla and Gynura procumbens.

6. The pharmaceutical composition of claim 5, wherein the red ginseng is prepared by the steps comprising: in the 1 st step, 2-10 years of rooting of ginseng selected from the group consisting of Panax notoginseng, Panax quinquefolius, Panax notoginseng, vietnamese ginseng, Panax elegator, Panax notoginseng and Panax notoginseng, is dried at 10 ℃ to 60 ℃ for 1 to 24 hours to prepare a 1 st dried ginseng; in the 2 nd step, the dried ginseng is washed with water and dried to remove moisture; steaming the dried ginseng at 60-120 ℃ for 1-48 hours in the 3 rd step to prepare a 1 st steamed ginseng; drying the 1 st steamed ginseng at 30-80 ℃ for 1-72 hours in the 4 th step to prepare a 1 st dried steamed ginseng having a water content of 40-70% (w/w); and, in the 5 th step, drying the 1 st dry steamed ginseng at 10 to 60 ℃ for 1 to 20 days to obtain final dried red ginseng having a water content of 10 to 20% (w/w).

7. The pharmaceutical composition of claim 1, wherein the combined herbal extract of common sage and red ginseng is prepared by a procedure comprising the steps of: in the step 1, the whole plant, root, stem or flower of common sage herb or red ginseng used as a basic extraction material is sliced and washed; in step 2, extracting material from the baseAdding 1-20 times of distilled water or C₁-C₄An extraction solvent selected from the group consisting of alcohols and mixtures thereof; in step 3, each solution is extracted by extraction with hot water, cold water or ultrasound for a period of 1-48 hours, preferably at a temperature of 50-120 ℃; repeating the above extraction process at step 4 to collect each filtrate with filtration, and drying by freeze-drying process, natural air-drying process or hot air-drying process, preferably freeze-drying process, to obtain dried extracts of each of the common sage herb and red ginseng; and mixing the respective dry extracts of the respective herbs at a mixing ratio (w/w) of 0.01-100:100-0.01(w/w) based on the dry weight of the respective herbs.

8. The pharmaceutical composition of claim 1, wherein the respiratory inflammatory disease is selected from the group consisting of: rhinitis, otitis media, pharyngolaryngitis, tonsillitis, pneumonia, asthma and COPD (chronic obstructive pulmonary disease).

9. A health functional food for preventing and treating respiratory inflammation diseases, comprising a combined herbal extract of Salvia plebeia and Ginseng radix Rubri as an active ingredient.

10. The health functional food according to claim 9, wherein the health functional food is provided as a powder, granule, tablet, capsule, pill, suspension, emulsion, syrup, tea bag, tea infusion or beverage type.

11. A health supplement food for preventing or improving respiratory inflammation diseases, comprising a combined herbal extract of Salvia plebeia and Ginseng radix Rubri as a main component.

12. A method of treatment comprising administering to a subject in need of treatment for a respiratory inflammatory disease a composition comprising a combined herbal extract of salvia plebeian and red ginseng.

13. Use of a combined herbal extract of common sage and red ginseng for the manufacture of a medicament for the treatment of respiratory inflammatory diseases in a human or mammal.

Technical Field

The present invention relates to a composition comprising a combined herbal extract of common sage herb and red ginseng as an active ingredient for preventing and treating respiratory inflammation and use thereof.

Background

In general, an inflammatory response is the normal response of a human body associated with edema, pain, etc., in the event that a tissue or cell receives any insult that results in some organic change in the tissue or cell. Recently, various cytokines have been found to be involved in inflammatory diseases.

The allergic reactions can be classified into four types (i.e., type I, type II, type III and type IV) according to the type of response, or two types (immediate type allergic reactions such as type I, type II or type III, and delayed type allergic reactions such as type IV) according to the type of time period from the time of hypersensitivity caused by the allergen to the time of onset of the reaction.

Among them, type I allergy involves IgE antibodies and is called allergy type allergy, leading to bronchial asthma, atopic diseases such as dermatitis or gastroenteritis, etc., allergic rhinitis such as hay fever, allergic conjunctivitis, food allergy, etc.

Asthma is considered to be a complex syndrome of the airways characterized by various clinical symptoms such as dyspnea caused by airflow obstruction, cough, acute or chronic airway inflammation, Airway Hyperresponsiveness (AHR), and structural remodeling, and can be reversibly or irreversibly restored. Most asthma is allergic disease and is characterized by chronic airway inflammation and bronchial hyperresponsiveness (Minoguchi K and Adachi M., Pathophysiology of asthma. in: Chernick NS, Altose MD, Homma I.edges. Rehabitation of the patient with respiratory disease. New York: McGraw-Hill, 1999, pp 97-104).

Asthma can be divided into two types, extrinsic asthma and intrinsic asthma. Exogenous asthma is caused by an exposed antigen and shows a positive response in a skin test or bronchial provocation test against the antigen. In general, the pathogenic age is younger and younger. It is mainly caused by house dust mites and pollen, animal epithelia, fungi, etc. Intrinsic asthma is caused by upper respiratory tract infections, exercise, emotional instability, humid climatic changes, and it is common for adult patients. In addition, the IgE antigen of exogenous asthma can be detected by skin tests due to the increase of IgE in serum.

As for pathophysiology, asthma is recognized by chronic inflammation driven by T helper type 2 (Th2) cells, and various inflammatory mediators such as cytokines, chemokines, signaling molecules, adhesion molecules, and growth factors from structural and immune cells in the airways are involved at various stages of asthma (Elias JA et al, J Clin invest, 111, pp 291-7, 2003). Activated inflammatory cells in the bronchi of patients with asthma (e.g., eosinophils, mast cells, alveolar macrophages, etc.) release various inflammatory mediators such as cysteine leukotrienes, prostaglandins, etc., and are involved in strong bronchoconstriction (MaggiE., Immunotecology 3, pp233-244, 1998; Pawankar R.curr. Opin. AllergyClin. Immunol., 1, pp3-6, 2001; Barnes PJ, et al, Phamacol. Rev.50, pp515-596, 1998).

Therefore, since the replication of various cytokines involved in the activation of inflammatory cells such as IL-4, IL-5, IL-13, etc. and IgE, and the replication of cysteine leukotriene released from inflammatory cells are major causes of inflammation, allergic reaction and asthma, there have been many studies to develop inhibitors from the replication of the foregoing substances.

COPD (chronic obstructive pulmonary disease) is reported to be one of the fifth leading causes of death worldwide in 2001, as well as a risk factor for cardiovascular morbidity and mortality. Based on the global initiative for Chronic Obstructive Pulmonary Disease (COLD) (FEV1 to FVC ratio less than 0.7), the prevalence of Chronic Obstructive Pulmonary Disease in Korean people over 45 years of age is 17.2% (male 25.8%, female 9.6%) (Dong Sonn Kim, Young Sam Kim, Ki-Suck Jung, Jung Hyun Chang, Chae-ManLim, Jae Ho Lee, Soo-Taek Uh, Jae Jeong Shim and Woo Jin Lew, representing Korean institute for tuberculosis and respiratory Disease, Am J Respir Crit Care Med Vol 172.pp 847, 2005; Don D.Sin and Bus.F.PallMan, cervical Disease a Risk Factor for cardiovascular Disease, McMahaland, McSum, mountain 1, McSonn D.S.F.M.S.S.S.S.S.S.S.P.S.S.S.P.S.S.S.E.P.S.M.S.S.E.P.S.P.S.P.S.S.S.P.S.S.S.E.S.S.E.E.P.E.E.E.S.E.E.S.E.S.S.S.S.S.E.S.S.S.S.S.S.E.E.S.S.E.S.S.S.S.S.S.S.S.S.S.S.E., todd ALee, Kevin B Weiss, Robert LJensen, Guy B Marks, Amund Gulsvik, EWA Nizankowska-Mogilnica, International variation in The prediction of COPD (The BOLD Study): a publication-based prediction Study, Lancet, Vol 370, 741. 750, September 1,2007).

Most patients with COPD have all 3 pathological mechanisms (chronic obstructive bronchitis, emphysema and mucus plugging) because they are caused by smoking, but they may differ in the proportion of emphysema and obstructive bronchitis. In developed countries, smoking is by far the most common cause of COPD, but there are some other risk factors including air pollution (especially indoor air pollution from burning fuel), poor diet and occupational exposure. COPD is characterized by an acceleration in the normal decline in lung function seen with age. Slowly progressing airflow limitation leads to disability and premature death, and is quite different from variable airway obstruction and symptoms (which progress less severely) in asthma.

The pathophysiological effects and syndromes of COPD and asthma are reported to be fundamentally different. Although both COPD and asthma are related to inflammation in the respiratory tract, there are significant differences in the nature of the inflammatory process, with differences in inflammatory cells, mediators, responses to inflammation, anatomical distribution, and responses to anti-inflammatory therapies, e.g., (a) in the case of inflammatory cells, mast cells, eosinophils, D4+ cells (Th2), macrophages, etc., primarily contribute to the development of asthma, while neutrophils, CD8+ (Tc), etc., primarily contribute to the development of COPD; (b) with respect to inflammatory mediators, leukotriene B, histamine, IL-4, IL-5, IL-13, eotaxin, RENTES, oxidative stress, etc. are mainly involved in the development of asthma, while TNF- α, IL-8, GRO- α, etc. are mainly involved in the development of COPD; (c) in terms of inflammatory syndromes, asthma shows inflammatory syndromes other than COPD such as AHR (airway hyperresponsiveness), epithelial detachment, fibrosis, non-parenchymal involvement, mucus secretion, relatively reversible airway obstruction, cough, sneeze, dyspnea, etc. by acting on the entire lung passageway at childhood, COPD occurs by acting on the peripheral airways at adulthood, and shows various phenomena such as epithelialization, parenchymal destruction, relatively irreversible airway obstruction, chronic bronchitis, emphysema, etc. (Barnes PJ (2000b) Mechanism in COPD: diferences from Thomas. chest 117 (Supl): 10S-14S; Saetta M, Turato G, Maestrelli P, Mace and Farri LM (2001) Cellular and structural medsides of respiratory diseases (am. J. Respir. C. 163. 1309: 1304).

It is reported that common sage (Salvia plebia R.Br.) belonging to the Labiatae family (Labiatae) and distributed in Korea contains flavones, homoplantagines, homoplantains, eupatorins, eupatorin-7-glucoside, etc. (B.S. Chung et al, Youngrim Press, 2 nd edition, Dohae HyangYakDaeSajeon, pp862-863, 1998).

Pharmaceutical compositions comprising an extract or purified fraction of litchi chinensis (litchi chinensis) for preventing or treating STAT 3-mediated diseases (Korean patent publication No.10-2013-0129868A) and compositions comprising extracts of a combination of turmeric (Curcuma longa), litchi chinensis, Triticum aestivum (Elymus mollis), Rhamnus velutipes (Chrysosporium Pilus var. valdelulosum), Rhamnus erythrophylla (Cyperus sanguinotella), Chrysosporium japonica (Chrysosporium japonica), Chrysosporium trayspermum and Chrysosporium liquidum (Chrysosporium liquidum) for preventing and treating allergic or non-allergic skin diseases as active ingredients have been reported (Korean patent publication No. 10-00220156579A).

Ginseng (ginseng) is reported to be a representative nutritional supplement in asian countries as well as in other countries around the world, and there are many plants of the genus panax belonging to the family Araliaceae (Araliaceae), for example: panax ginseng (Panax ginseng), american ginseng (Panax quinquefolia), chinese Panax ginseng (Panax notogeng), american ginseng (Panax trifolia) in the eastern north america, japanese ginseng (Panax japonica), nipagin ginseng (Panax pseudoginseng), vietnam ginseng (Panax vietnamensis), Panax elegator, Panax ginseng (Panax wanginsenus) and pinnacle Panax ginseng (Panax bipinnatidus), and the like, which are distributed or cultivated in the eastern asian region.

The most important component in the plant belonging to the genus Panax is dammarane saponin having 1-4 saccharides, and particularly Korean ginseng (Korean ginseng) contains a large amount of ginsenoside such as ginsenoside Rb1, Rb2, Rc, Rd, Rg1, Re, etc. These saponins exhibit various efficacies and pharmacological activities according to their structures.

There have been many attempts to process or modify the genus Panax plants (particularly, the structure of ginsenoside therein) to increase their pharmacological efficacy, and the main component of Panax plants is dammarane saponin such as ginsenoside Rb₁、Rb₂、Rc、Rd、Rg₁And Re, the activities of which differ from each other according to their chemical structures (Chung B.S. and Shin M.K.; HyangyakDaesaccon, Youngrimsa, pp439-442, 1998).

In korea, ginseng is classified into several types according to processing methods, namely, unprocessed natural ginseng cultivated for more than 4 years (called fresh ginseng), ginseng simply processed (e.g., the cortex of fresh ginseng is removed) (called white ginseng), ginseng cultivated for more than 6 ages (called red ginseng) through complex processing (i.e., the processing steps consist of the 1 st steaming with steam at about 130 ℃ for 1 or 2 hours, cooling with air, the 2 nd steaming with steam at about 70 ℃ for 7-10 hours, removing unnecessary parts such as fibrous roots, etc., and drying in a drying room so that the water content of ginseng is between 12.5-13.5%), which is the most expensive and pharmacologically active form of ginseng.

It is reported that red ginseng processed by the above-mentioned high-temperature treatment contains various unique and improved ginsenosides, such as ginsenoside Rg, which are not found in fresh ginseng or white ginseng₂、Rg₃、Rg₅、Rh₂、Rh₃、Rh₄、Rs₁、Rs₂、Rs₃Et al (Bae E.A. et al, 2006, inhibition effect of a Korean red and its genes regulating peptides Rg3, Rf and Rh2 in a motor driven food and drink reaction and contact chemistry model, biol. Pharm. Bull, 29, pp 1862-1867).

The present inventors developed effective agents for treating respiratory inflammatory diseases from various herbal medicines, such as specific extract isolated from Leonurus sibiricus (Leonurus sibiricus) as an active ingredient for preventing or treating respiratory inflammatory diseases (Korean patent registration No.10-1770766B 2); specific extracts or compounds isolated from biota orientalis (Thuja orientalis) as active ingredients for preventing or treating respiratory inflammatory diseases (Korean patent laid-open No. KR 10-2016-0021038A), and the like.

However, in any of the above-cited documents, the disclosures of which are incorporated herein in their cited forms, there has been no report or disclosure regarding the therapeutic effect of the above-described extract of the combined herbs consisting of salvia plebeian and red ginseng on respiratory inflammatory diseases.

Disclosure of Invention

Technical problem

Accordingly, the present inventors have made efforts to find an effective herbal preparation for the treatment and prevention of respiratory inflammation diseases, and the combined herbal composition shows a more effective therapeutic effect on respiratory inflammation than the herbal composition alone, which effect is confirmed by various experiments, for example, the number of cells of BAL (bronchoalveolar lavage fluid) (experimental example 1) is determined to confirm a synergistically effective inhibitory activity on the number of cells in BAL (bronchoalveolar lavage fluid); determining the CD11b +/Gr-1+ ratio in leukocytes in BAL fluid (Experimental example 2) to confirm a synergistically effective inhibitory activity against the CD11b +/Gr-1+ ratio in leukocytes in BAL fluid; determining the RNA expression level of inflammatory cytokines in lung tissue (experimental example 3) to confirm a synergistically effective inhibitory activity on the RNA expression level of inflammatory cytokines in lung tissue; determining the RNA expression level of inflammatory cytokines in BALF (experimental example 4) to confirm a synergistically effective inhibitory activity on the RNA expression level of inflammatory cytokines in BALF; lung histology (experimental example 5) to confirm anti-asthmatic effect by histopathological analysis of broncho-alveolar tissues; clinical tests (experimental example 7) were briefly conducted to confirm the clinical efficacy and safety of the extract of the present invention against respiratory diseases in humans, etc. The combined extract of the present invention has been confirmed to show a more effective inhibitory effect on respiratory inflammatory diseases than the respective herbal extracts. Therefore, the herbal extract of the present invention can be effectively used in pharmaceutical compositions, health functional foods and health supplement foods for preventing and treating respiratory inflammatory diseases.

Technical scheme

The technical solution to solve the problems of the background art is to develop a novel herbal formulation for treating and preventing respiratory inflammatory diseases.

According to one aspect, the present invention provides a pharmaceutical composition for preventing and treating respiratory inflammatory diseases, comprising a combined herbal extract of salvia plebeian and red ginseng as an active ingredient.

The present invention also provides a health functional food for preventing or improving respiratory inflammation diseases, which comprises a combined herbal extract of Salvia plebeia and Ginseng radix Rubri as an active ingredient.

The term "combined herbal extract" as defined herein includes a combined herbal extract, i.e., a combined herbal extract of common sage and red ginseng in the present invention having the following mixing ratio (w/w) based on the dry weight of each extract: 0.01-100:100-0.01(w/w), preferably 0.1-50:50-0.1(w/w), more preferably 0.5-20:20-0.5(w/w), still more preferably 1-10:10-1(w/w), most preferably 1-5:5-1 (w/w).

In particular, the term "extract" as defined herein includes soluble in distilled water, C₁-C₄An alcohol or a mixture thereof (preferably water, ethanol or a mixture thereof, more preferably water or an aqueous 10% -90% (v/v) ethanol solution, most preferably water or an aqueous 20-80% (v/v) ethanol solution).

The term "common sage" or "red ginseng" as defined herein includes the entire plant, root, stem or flower of "common sage" or "red ginseng" used as the base extraction material.

The term "red ginseng" as defined herein includes processed ginseng having 2-10 years of rooting, preferably 3-8 years of rooting, more preferably 5-7 years of rooting, having ginseng selected from the group consisting of: radix seu folium Gynurae Yunnanensis, radix Panacis Quinquefolii, Notoginseng radix, Vietnamese Ginseng radix, Panax elegator, Gynura macrophylla and Gynura procumbens.

Specifically, the term "red ginseng" as defined herein includes processed ginseng prepared by the steps comprising: in the 1 st step, 2-10 years of rooting (preferably 3-8 years of rooting, more preferably 5-7 years of rooting) of ginseng selected from the group consisting of Panax notoginseng, Panax quinquefolius, Panax notoginseng, vietnamese ginseng, Panax elegator, Panax notoginseng and Panax notoginseng leaf is dried at 10 ℃ -60 ℃ (preferably room temperature) for 1-24 hours (preferably 1-3 hours) to prepare a 1 st dried ginseng; in the 2 nd step, the dried ginseng is washed with water and dried to remove moisture; steaming the dried ginseng at 60 to 120 ℃ (preferably 80 to 110 ℃) for 1 to 48 hours (preferably 1 to 12 hours, more preferably 1 to 3 hours) at step 3 to prepare 1 st steamed ginseng; drying the 1 st steamed ginseng at 30 to 80 ℃ (preferably 40 to 70 ℃) for 1 to 72 hours (preferably 2 to 48 hours, more preferably 4 to 12 hours) at 4 step to prepare the 1 st dried steamed ginseng having a water content of 40 to 70% (w/w) (preferably 45 to 55% (w/w)); and, in the 5 th step, the 1 st dry steamed ginseng is dried at 10 to 60 ℃ (preferably 15 to 35 ℃) for 1 to 20 days (preferably 6 to 20 days) to obtain the final dried red ginseng having a water content of 10 to 20% (w/w) (preferably 12 to 17% (w/w)).

The term "combined herbal extract of common sage and red ginseng" as defined herein may be prepared by a procedure comprising the following steps: in step 1, the whole plant, root, stem or flower of 'litchi grass' or 'red ginseng' used as a basic extraction material is sliced and washed; in step 2, adding 1-20 times (preferably 4-8 times) volume of a solvent selected from distilled water, C, to the base extraction material₁-C₄An extraction solvent of the group consisting of alcohol or a mixture thereof (preferably water, ethanol or a mixture thereof); in the 3 rd step, hot water extraction and cold water extraction are carried outExtracting each solution with an extraction method such as extraction with hot water at a temperature of 50-120 deg.C, preferably about 80-100 deg.C or ultrasonic extraction for a period of 1-48 hours (preferably 2-24 hours); repeating the above extraction process at step 4 to collect each filtrate with filtering, and drying by freeze drying, natural air drying or hot air drying process (preferably freeze drying process) to obtain dried extracts of each of the common sage and red ginseng; and mixing the respective dry extracts of the respective herbs (salvia plebeia and red ginseng) at a mixing ratio of 0.01-100:100-0.01(w/w), preferably 0.1-50:50-0.1(w/w), more preferably 0.5-20:20-0.5(w/w), more preferably 1-10:10-1(w/w), most preferably 1-5:5-1(w/w)), based on the dry weight (w/w) of each herb, to prepare the inventive combined extract of the present invention.

Specifically, the term "inflammatory disease of the respiratory tract" disclosed herein includes all inflammatory diseases of the respiratory tract, for example, it is not intended to be limited to rhinitis, otitis media, pharyngolaryngitis, tonsillitis, pneumonia, asthma, COPD (chronic obstructive pulmonary disease), and the like.

The herbal extract of the present invention can be prepared according to the following preferred embodiments.

For example, the present invention also provides a process for preparing the herbal extract of the present invention, said process comprising the steps of: in step 1, the whole plant, root, stem or flower of 'litchi grass' or 'red ginseng' used as a basic extraction material is sliced and washed; in step 2, adding 1-20 times (preferably 4-8 times) volume of a solvent selected from distilled water, C, to the base extraction material₁-C₄An extraction solvent of the group consisting of alcohol or a mixture thereof (preferably water, ethanol or a mixture thereof); in step 3, extracting each solution by an extraction method of hot water extraction, cold water extraction or ultrasonic extraction (preferably, hot water extraction at a temperature of 50 ℃ to 120 ℃, preferably about 80 ℃ to 100 ℃) for a period of 1 to 48 hours (preferably 2 to 24 hours); repeating the above extraction process at step 4 to collect each filtrate with filtering, and drying by freeze drying, natural air drying or hot air drying process (preferably freeze drying process) to obtain dried extracts of each of the common sage and red ginseng;and mixing the respective dry extracts of the respective herbs (salvia plebeia and red ginseng) at a mixing ratio of 0.01-100:100-0.01(w/w), preferably 0.1-50:50-0.1(w/w), more preferably 0.5-20:20-0.5(w/w), more preferably 1-10:10-1(w/w), most preferably 1-5:5-1(w/w), based on the dry weight (w/w) of each herb, to prepare the inventive combined extract of the present invention.

It is another object of the present invention to provide a process for preparing the extract of the present invention as described above for preparing a composition effective in treating or preventing a disease of interest.

It is another object of the present invention to provide a pharmaceutical composition or health functional food for preventing and treating respiratory inflammatory diseases, which comprises the herbal extracts of the above herbs as active ingredients, obtained by the process as described above.

The inventive composition of the present invention showed an effective therapeutic effect on respiratory inflammatory diseases, which was confirmed by various experiments, for example, determining the cell number of BAL (bronchoalveolar lavage fluid) (experimental example 1) to confirm a synergistically effective inhibitory activity on the cell number in BAL (bronchoalveolar lavage fluid); determining the CD11b +/Gr-1+ ratio in leukocytes in BAL fluid (Experimental example 2) to confirm a synergistically effective inhibitory activity against the CD11b +/Gr-1+ ratio in leukocytes in BAL fluid; determining the RNA expression level of inflammatory cytokines in lung tissue (experimental example 3) to confirm a synergistically effective inhibitory activity on the RNA expression level of inflammatory cytokines in lung tissue; determining the RNA expression level of inflammatory cytokines in BALF (experimental example 4) to confirm a synergistically effective inhibitory activity on the RNA expression level of inflammatory cytokines in BALF; lung histology (experimental example 5) to confirm anti-asthmatic effect by histopathological analysis of broncho-alveolar tissues; clinical tests (experimental example 7) were briefly conducted to confirm the clinical efficacy and safety of the extract of the present invention against respiratory diseases in humans, etc. The combined extract of the present invention has been confirmed to show a more effective inhibitory effect on respiratory inflammatory diseases than the respective herbal extracts. Therefore, the herbal extract of the present invention can be effectively used in pharmaceutical compositions, health functional foods and health supplement foods for preventing and treating respiratory inflammatory diseases.

The pharmaceutical composition for treating the disease of interest may contain about 0.01 w/w% to 99 w/w% of the above herbal extracts of the present invention based on the total weight of the composition.

However, the amount and components of the above composition may vary depending on the condition of the patient, the disease progression of the patient, the kind of disease, and the like.

Depending on the method of use, the compositions of the present invention may additionally comprise conventional carriers, adjuvants or diluents.

The herbal composition according to the invention may be formulated as: oral dosage forms such as powder, granule, tablet, capsule, suspension, emulsion, syrup, aerosol, etc.; a topical formulation; or an injection solution. The herbal composition according to the invention may be provided as a pharmaceutical composition containing a pharmaceutically acceptable carrier, adjuvant or diluent, such as lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, magnesium stearate and mineral oil. The formulation may additionally comprise excipients such as fillers, bulking agents, binders, wetting agents, disintegrants, surfactants, diluents and the like. The solid oral dosage form includes tablets, pills, powders, granules, capsules, etc., and is prepared by adding at least one excipient such as starch, calcium carbonate, sucrose, lactose, gelatin, etc., to the herbal extract. Lubricating agents such as magnesium stearate or talc may be used. Aqueous oral dosage forms include suspensions, oral solutions, emulsions, syrups, and aqueous oral dosage forms may contain several excipients such as wetting agents, sweetening agents, preservatives, and water, liquid paraffin. Parenteral dosage forms include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations, suppositories, and the like. Suitable examples of carriers include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate. The base of the suppository may include witepsol, polyethylene glycol, tween 61, cocoa butter, glyceryl laurate, glycerogelatin, and the like, but is not limited thereto.

The desired dosage of the composition of the present invention varies depending on the weight and condition of the subject, severity, pharmaceutical form, time and route of administration, and can be selected by one skilled in the art. However, in order to obtain the desired effect, it is generally recommended to administer the inventive composition in an amount of from 0.01mg/kg weight/day to 10g/kg weight/day, preferably from 1mg/kg weight/day to 1g/kg weight/day. The dose can be administered in a single dose or in multiple doses per day.

The pharmaceutical composition according to the present invention can be administered to a subject animal such as a mammal (rat, mouse, livestock or human) by various routes. All modes of administration are contemplated, e.g., administration may be oral, rectal or by intravenous injection.

It is another object of the present invention to provide a method for treating or preventing respiratory inflammatory diseases, which comprises administering a composition comprising a combined herbal extract of common sage and red ginseng as an active ingredient to a subject in need of treatment or prevention of respiratory inflammatory diseases.

Another object of the present invention is to provide use of a combined herbal extract of salvia plebeian and red ginseng as an active ingredient for the manufacture of a medicament for treating or preventing respiratory inflammatory diseases in humans or mammals.

According to one aspect of the present invention, there is provided a health functional food comprising a combined herbal extract of salvia plebeian and red ginseng for preventing or improving respiratory inflammatory diseases as an active ingredient.

The term "health functional food" as defined herein includes a functional food having an enhanced function (such as a physical function or a physiological function) by adding the extract of the present invention to a conventional food to prevent or improve a target disease in a human or a mammal, and specified by korean health functional food law 6727.

The health functional food composition for preventing and improving a disease of interest may contain about 0.01 to 95 w/w%, preferably 1 to 80 w/w%, of the above-mentioned herbal composition of the present invention based on the total weight of the composition.

In addition, the inventive extract can be used as a main component or an additive and an adjuvant in the preparation of various functional health foods and health supplement foods for preventing or improving respiratory inflammatory diseases.

The health functional food of the present invention can be prepared and processed in the form of pharmaceutically acceptable dosage forms (e.g., powders, granules, tablets, capsules, pills, suspensions, emulsions, syrups, etc.) or functional health food forms (e.g., tea bags, tea infusions, types of health beverages, etc.).

It is another object of the present invention to provide a health supplement food for preventing or improving respiratory inflammatory diseases, which comprises a combined herbal extract of common sage and red ginseng as a main component.

The above term "as a main component" means that the above health supplement food contains about 30 to 99 (w/w%), preferably 50 to 99 (w/w%), more preferably 70 to 99 (w/w%), of the extract of the present invention based on the total weight of the composition.

When the combined herbal extract of the present invention is used as a component in a health functional beverage composition, the health functional beverage composition may include other components such as a flavoring agent or natural carbohydrates without limitation similar to typical beverage compositions. Examples of natural carbohydrates include monosaccharides such as glucose, fructose, and the like; disaccharides such as maltose, sucrose, and the like; and polysaccharides such as sugars (e.g., dextrins, cyclodextrins); and sugar alcohols such as xylitol, sorbitol, erythritol. Natural flavoring agents (thaumatin, stevia extracts (rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be added to the functional health beverage composition the amount of natural carbohydrates is typically from about 1g to 20g, preferably from about 5g to 12g, per 100ml of the present composition.

When the combined herbal extract of the present invention is used as a food additive for health foods, the combined herbal extract may be added in its entirety or used together with other food ingredients according to the usual processes. Examples of food products include meat products, sausages, bread, chocolate, candy, snacks, crackers, soft-baked biscuits, pizza, stretched noodles, noodle products, chewing gum, dairy products such as ice cream, soups, beverages, tea, drinks, alcoholic drinks, vitamin complexes, etc. for preventing or ameliorating a disease of interest, but are not intended to be limited thereto.

Other components than the aforementioned compositions are various nutrients, vitamins, minerals or electrolytes, synthetic flavors, colorants and modifiers (in the case of cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid binders, pH control agents, stabilizers, preservatives, glycerin, alcohol, carbonation used in carbonated beverages, and the like. Other components than the aforementioned components may be fruit juices used for preparing natural fruit juices, fruit juice beverages, and vegetable beverages, wherein the components may be used alone or in combination. The ratio of the components is not critical but is generally from about 0 to 20 w/w% per 100 w/w% of the present composition.

Further, the above extract can be added to foods or drinks for preventing and improving the objective disorders. The amount of the above-mentioned extract in a food or beverage as a functional health food or health supplement food may be generally about 0.01 w/w% to 15 w/w% of the total weight of the food for functional health food composition. Also, the extract of the present invention may be added in an amount of 0.02g to 5g, preferably 0.3g to 1g, per 100ml of the health drink composition.

Advantageous effects

As described in the present invention, the combined herbal composition of the present invention showed effective therapeutic effect on respiratory inflammation diseases, and the combined herbal composition showed more effective therapeutic effect on respiratory inflammation than the herbal composition alone, which was confirmed by various experiments, such as determination of cell number of BAL (bronchoalveolar lavage) (experimental example 1); determining the CD11b +/Gr-1+ ratio in leukocytes in BAL fluid (Experimental example 2); determining the RNA expression level of inflammatory cytokines in lung tissue (experimental example 3); determining the RNA expression level of inflammatory cytokines in BALF (experimental example 4); lung histology (experimental example 5); brief clinical tests (Experimental example 7) and the like have confirmed that the combined extract of the present invention shows a more effective inhibitory effect on respiratory inflammatory diseases than the respective herbal extracts. Therefore, the herbal extract of the present invention can be effectively used in pharmaceutical compositions, health functional foods and health supplement foods for preventing and treating respiratory inflammatory diseases.

Drawings

FIG. 1 shows histopathological analysis of broncho-alveolar tissues stained by stain (NC: normal control group; AIG: group in which asthma is induced; CB 3: group of test samples treated with CB3 combination extract).

Detailed Description

It will be apparent to those skilled in the art that various modifications and variations can be made in the compositions, uses and formulations of the present invention without departing from the spirit or scope of the invention.

The present invention is more specifically explained by the following examples. It should be understood, however, that the present invention is not limited to these examples in any way.