Composition based on elderberry and application of composition in elimination of pulmonary nodules

Abstract

The invention provides a composition based on elderberry and application of the composition to elimination of pulmonary nodules. The composition is prepared from an elderberry extract, a radix salviae miltiorrhizae extract, a sophora flower bud extract, beta-glucan, menthol and curcumin. The composition provided by the invention carries multiple components, multiple targets and multiple regulatory pathways to interact in a preparation. On one hand, the composition can inhibit generation and release of inflammatory factors by regulating oxidative stress, and on the other hand, the composition can prevent and eliminate pulmonary nodules by blocking generation of angiotensin II, inhibiting vascular hyperplasia and inflammatory response and regulating immunosuppression inflammation. The oral preparation described in the invention can be a drug loading system such as a capsule, a tablet, a granule, a suspension or an emulsion.

Description

Technical Field

[0001] The present invention belongs to the field of medicine, relates to a composition based on elderberry and application thereof in eliminating lung nodules, and is application of the elderberry composition in preparing a medicine for eliminating lung nodules. Technical Background

[0002] Sarcoidosis is a systemic disease characterized by sterile granulomatous inflammation in affected organs. While its etiology remains unclear, the disease has characteristic clinical and immunologic features. Although sarcoidosis can affect nearly any organ in the body, the lungs and lymph nodes are most commonly affected. Although the inflammatory infiltrate in pulmonary sarcoidosis can remit, persistent disease activity is common and can lead to pulmonary fibrosis in severe cases.

[0003] With the acceleration of population aging, environmental pollution, changes in lifestyle, improved CT resolution, the popularization of low-dose CT screening and the enhancement of people's awareness of physical examinations, the number of asymptomatic lung nodules detected is increasing, the size of nodules is getting smaller, and the density is getting lighter. The detection rate has risen to 22% to 51%.

[0004] In general, in addition to age factors, the main causes of pulmonary nodules are as follows: Smoking and secondhand smoke: Long-term exposure to various carcinogens in cigarettes and cigars can lead to chronic bronchitis, emphysema, chronic obstructive pulmonary disease, and other problems. These can eventually lead to lung nodules or lung cancer. Air pollution caused by various industrialization and automobile exhaust can irritate the respiratory system and lead to lung nodules or lung cancer. Indoor pollution: such as decoration paint, kitchen fumes, various irritating kitchen and bathroom cleaning products, etc., will irritate organs such as the trachea and lungs; Inflammatory reaction: fibrosis, granuloma, calcified nodules and other inflammations; Lung infections caused by low immunity: such as tuberculosis, pneumonia, fungal infections, etc.

[0005] Pulmonary nodules can be solitary or multiple depending on the number. Clinically, they can be divided into inflammatory nodules and viral nodules according to the nature of the nodules, and the majority are inflammatory pulmonary nodules. In the early stages of pulmonary nodules, there are often no obvious symptoms and signs. Cough, a small amount of sputum, and occasionally a small amount of hemoptysis may occur. There may also be symptoms such as fatigue, fever, night sweats, loss of appetite and weight loss. The condition may be aggravated by concurrent infection with emphysema, bronchiectasis, cor pulmonale, etc. The existing treatment for inflammatory pulmonary nodules mainly uses antibiotics to reduce inflammation. The long-term and large-scale use of antibiotics to treat small nodule inflammatory lesions carries the risk of abuse of antibiotics and is also ineffective.

[0006] Traditional Chinese Medicine believes that lung nodules are tangible evils, mainly formed by the interaction of phlegm, blood stasis, and toxins. When the nodules grow larger and develop into a combined infection, they will show some syndromic characteristics, which may include the syndromes of qi stagnation and phlegm obstruction, cold phlegm stagnation, damp-heat phlegm and blood stasis, yang deficiency and internal heat. Although traditional Chinese medicine has unique advantages in preventing and treating lung diseases, its specific mechanism of action remains unclear. Modern medical research on the mechanism of lung nodules is as follows:

[0007] Activation of inflammatory mediators: The formation of pulmonary nodules is closely related to the inflammatory response in the lungs. Inflammatory mediators such as cytokines (such as IL-1β, IL-6, TNF-α, etc.) and chemokines (such as CCL2, CCL5, CXCL10, etc.) are activated and released. These mediators can attract immune cells to the lungs, causing local inflammation and tissue damage, which in turn promotes the formation of pulmonary nodules.

[0008] Infiltration of immune cells: During inflammatory responses, immune cells such as T cells and macrophages are recruited to the lungs. These cells participate in the formation and development of lung nodules by releasing inflammatory mediators and direct cell-cell interactions.

[0009] Granuloma formation: During the formation of pulmonary nodules, macrophages and lymphocytes aggregate to form granulomas, a characteristic feature of pulmonary nodules. Granuloma formation may be a defensive response to certain antigens or pathogens, but excessive or persistent granuloma formation can lead to lung tissue damage and fibrosis. Nodules are essentially inflammatory immune granulomas, and their formation is positively correlated with angiotensin-converting enzyme (ACE) activity. Blocking the production of angiotensin II (ACE-2) can inhibit vascular proliferation and inflammatory responses.

[0010] The role of oxidative stress: Reactive oxygen species (ROS) play a key role in the inflammatory response and the formation of pulmonary nodules. ROS can be produced by inflammatory cells, such as macrophages and neutrophils, and they can oxidize intracellular biomolecules such as lipids, proteins, and DNA, leading to cell damage and death. In addition, ROS can activate transcription factors such as NF-κB, further promoting the production and release of inflammatory mediators, exacerbating the inflammatory response and the formation of pulmonary nodules.

[0011] Natural plant extracts or active components of natural plants can inhibit inflammatory responses and dissipate lung nodules by regulating inflammatory mediators, reducing the release of inflammatory factors, and regulating reactive oxygen species. Targeting the pathogenesis of lung diseases, it is necessary to develop extract compositions containing active ingredients to achieve the dissipation and elimination of lung nodules through multiple targets and mechanisms. Summary of the Invention

[0012] The technical problem to be solved by the present invention is to address the deficiencies of the existing technology and provide a composition based on elderberry, which is a natural plant extract composition based on elderberry, and the composition is used for preventing, treating and eliminating pulmonary nodules.

[0013] The invention provides an elderberry-based composition for preventing, treating and eliminating pulmonary nodules, which consists of elderberry extract, salvia miltiorrhiza extract, sophora japonica flower extract, curcumin, menthol and beta-glucan.

[0014] By adopting the above-mentioned technical scheme, the elderberry extract is rich in bioflavonoids, anthocyanins, vitamins, omega-3 vegetable oils, cyanidin-3-glucoside, and cyanidin-3-sambubioside. Elderberry (Sambucus nigra L.) extract has been shown to promote anti-inflammatory and cellular antioxidant activities. In lipopolysaccharide-stimulated RAW 264.7 cells pre-exposed to elderberry extract, it exhibited a dose-dependent inhibition of nitric oxide release, demonstrating anti-inflammatory activity. Regarding cellular antioxidant protection, pre-exposure of HepG2 and Caco-2 cells to elderberry extract (50 μg / mL) prevented up to 90% of tert-butyl hydroperoxide (t-BOOH)-induced toxicity. In Caco-2 cells, elderberry extract prevented glutathione depletion, reactive oxygen species production, abnormal morphological changes, and DNA fragmentation in response to t-BOOH oxidative damage. These results suggest that elderberry has high potential for reducing cellular oxidative stress and preventing inflammatory processes.

[0015] By adopting the above technical solution, the sophora japonica extract refers primarily to substances extracted from the flower buds of the sophora japonica tree, specifically a compound called quercetin. Quercetin has anti-inflammatory, antioxidant, and apoptosis-promoting properties, which suggest it could have a positive impact on the formation and development of lung nodules. For example, quercetin may work by inhibiting nodular reactions, reducing inflammation, and maintaining lung health.

[0016] By adopting the above technical solution, the main active ingredients of the Danshen extract include luteolin, salvianolic acid, danshensu and tanshinone, etc., which have multiple functions of anti-inflammatory, antioxidant, anticoagulant and improving blood circulation, and can play its role in preventing and treating pulmonary fibrosis through multiple components, multiple targets and multiple pathways. In the treatment of pulmonary fibrosis, Danshen mainly intervenes in key links such as oxidative stress, inflammatory damage, epithelial-mesenchymal transition, fibroblast activation, extracellular matrix accumulation and metabolic regulation. Its mechanism of action involves signaling pathways such as NF-κB, TGF-β1 / Smad, PI3K / Akt, MAPK, Nrf2 and AMPK. Related factors include TGF-β, ACE-2, ANG-(1-7), TNF-α and IL-6. For example, tanshinone IIA can inhibit angiotensin II by regulating the MAPK signaling pathway, thereby inhibiting vascular proliferation and inflammatory response, regulating immune suppression and inflammation, and thus achieving the prevention and elimination of lung nodules.

[0017] By adopting the above technical solution, the curcumin is a natural polyphenol compound extracted from turmeric. Curcumin can regulate various inflammatory factors, such as cyclooxygenase (COX-2), interleukins (IL-1, IL-6, IL-12), TNF-α, IFN-γ and NF-κB, etc., to reduce lung inflammatory response. By reducing the level of inflammation, curcumin has a positive effect on the treatment of lung nodules. Curcumin can also react with glutathione (GSH) in cells to generate new antioxidants to remove peroxides and protect cells from damage. The formation of lung nodules is closely related to oxidative stress, so the powerful antioxidant activity of curcumin helps to inhibit the development of nodules.

[0018] In some embodiments, the weight ratio of each component in the composition, namely, elderberry extract, salvia miltiorrhiza extract, sophora japonica extract, curcumin, menthol and β-glucan, is 20-30:4-10:10-18:14-18:0.1-1:5-15.

[0019] In some embodiments, the weight portion of the elderberry extract is 20 to 30 parts by weight, preferably 23 to 27 parts by weight.

[0020] In some embodiments, the amount of the Salvia miltiorrhiza extract is 4 to 10 parts by weight, preferably 6 to 8 parts by weight.

[0021] In some embodiments, the weight portion of the Sophora japonica flower extract is 10 to 18 parts by weight, preferably 12 to 16 parts by weight.

[0022] In some embodiments, the amount of curcumin is 14 to 18 parts by weight, preferably 15 to 17 parts by weight.

[0023] In some embodiments, the menthol is present in an amount of 0.1 to 1 part by weight, preferably 0.2 to 0.8 part by weight.

[0024] In some embodiments, the β-glucan is present in an amount of 5 to 15 parts by weight, preferably 8 to 12 parts by weight.

[0025] The Danshen extract contains fat-soluble tanshinones and water-soluble phenolic acid components. The fat-soluble components include: Tanshinone IIA, Tanshinone I, Cryptotanshinone, Dihydrotanshinone, etc.; the water-soluble components include: Danshensu, Salvianolic Acid B, Protocatechuic Aldehyde, Rosmarinic Acid, etc. Among them, the fat-soluble components have low oral absorption and utilization. The Sophora japonica extract is derived from Sophora japonica, which is a traditional Chinese medicine with the effects of clearing heat and cooling blood, stopping bleeding and anti-inflammation. However, the beneficial components in the extract, such as rutin and quercetin, are poorly soluble in water and also have relatively low absorption when preparing oral preparations. The curcumin is a class of hydrophobic acidic compounds extracted from turmeric (Curcuma longa L.) with multiple biological activities such as anti-inflammatory and antioxidant. However, due to various reasons such as poor water solubility, unstable chemical properties, and rapid degradation under physiological conditions, curcumin also has extremely low bioavailability. Therefore, the present invention adopts lipid microencapsulation technology, which can significantly promote the membrane permeability of fat-soluble components, effectively improve bioavailability, and enhance its anti-inflammatory and anti-inflammatory effects.

[0026] Another object of the present invention is to provide use of the composition in preparing a drug for eliminating pulmonary nodules.

[0027] The medicine is prepared from the composition and pharmaceutically acceptable excipients.

[0028] The drug regulates oxidative stress, inhibits the production and release of inflammatory factors, and on the other hand, can prevent and eliminate lung nodules by blocking the generation of angiotensin II, inhibiting vascular proliferation and inflammatory response, and regulating the immune system to suppress inflammation.

[0029] The drug is mainly used to prevent, treat and eliminate lung nodules, and also has preventive and therapeutic effects on other lung diseases, including the prevention and treatment of lung injury, prevention and treatment of pulmonary fibrosis, prevention and treatment of pulmonary edema, prevention and treatment of asthma, and prevention and treatment of chronic pulmonary obstructive pulmonary disease; the lung injury is acute lung injury and / or pulmonary fibrosis.

[0030] The excipients include adhesives, suspending agents or thickening agents, disintegrants, fillers, solubilizers, stabilizers, lubricants, wetting agents, flavoring agents, etc.

[0031] The composition may further include a binder, which includes but is not limited to one or more of povidone K30, povidone K29 / 32, hydroxypropyl methylcellulose, hydroxypropyl cellulose, starch, maltodextrin, and sucrose.

[0032] The composition may also include a disintegrant. Disintegrants aid in the breakdown or decomposition of a substance. The term "disintegrate" includes the dissolution and dispersion of a dosage form upon contact with gastrointestinal fluids. Examples of disintegrants include, but are not limited to, starches such as one or more of pregelatinized starch, sodium starch glycolate, crosslinked sodium carboxymethyl cellulose, and crosslinked polymers.

[0033] In some embodiments, the compositions described herein may further include a filler, including but not limited to one or more of lactose, calcium phosphate, microcrystalline cellulose, starch, maltodextrin, and mannitol.

[0034] In some embodiments, the composition described herein may further include a lubricant, including but not limited to one or more of stearic acid, talc, micronized silica gel, sodium stearyl fumarate, hydrogenated vegetable oil, magnesium stearate, and glyceryl behenate.

[0035] In some embodiments, the compositions described herein may further include a plasticizer. Plasticizers include, but are not limited to, compounds used to soften the microcapsule material or film coating to make it less brittle. Suitable plasticizers include PEG 300, PEG 400, PEG 2000, PEG 3350, propylene glycol, oleic acid, and triacetin. Plasticizers may also serve as wetting agents.

[0036] In some embodiments, the compositions as described herein may further include a solubilizing agent. The solubilizing agent includes, but is not limited to, one or more of medium chain triglycerides, olive oil, triacetin, ethyl caprylate, N-methylpyrrolidone, hydroxypropyl cyclodextrin, ethanol, isopropyl alcohol, polyethylene glycol 300, polyethylene glycol 400, and propylene glycol.

[0037] In some embodiments, the compositions described herein may further include a stabilizer. Stabilizers include, but are not limited to, any antioxidant, buffer, preservative, or other compound. Typical stabilizers include one or more of L-arginine, citric acid, benzyl alcohol, phenol, propylene glycol, m-cresol, and tromethamine.

[0038] In some embodiments, the compositions described herein may further include a suspending agent or thickening agent. Suspending agents or thickening agents include, but are not limited to, one or more of polyvinyl pyrrolidone, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, sodium alginate, chitosan, gum arabic, guar gum, and xanthan gum. In some embodiments, the compositions described herein may further include flavoring agents. Flavoring agents include, but are not limited to, fruit essences, acesulfame potassium, glucose, fructose, sucrose, maltose, starch sugar, and lactose, as well as one or more of stevioside, glycyrrhizin, simple syrup and aromatic syrup, saccharin sodium, sucralose, aspartame, neotame, glycerin, sorbitol, mannitol, and citric acid.

[0039] The dosage form of the medicine is an oral preparation.

[0040] Alternatively, the oral dosage form may include the elderberry extract, β-glucan and microcapsule particles (containing salvia miltiorrhiza extract, sophora japonica extract, curcumin and menthol) described herein and other acceptable (eg, physiologically acceptable) excipients.

[0041] The microcapsule particles are prepared by using lipid microencapsulation technology to prepare salvia miltiorrhiza extract, sophora japonica flower extract, menthol and curcumin, so as to improve membrane permeability and thus increase bioavailability.

[0042] The compositions as described herein are administered as one or more capsules. In some embodiments, the dosage is a single capsule, two capsules, three capsules or more. In some embodiments, the capsule comprises an amount of the composition as described herein of at least or about 100 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 850 mg, 850 mg, 900 mg, 950 mg, 1000 mg, or includes and / or spans the range of the above values. For example, the capsule can comprise an amount of 300 mg to 400 mg, 250 mg to 500 mg, 350 mg to 400 mg, etc. In some embodiments, the capsule comprises about 400 mg of the composition as described herein.

[0043] The drug is achieved by the following steps: (1) Salvia miltiorrhiza extract, Sophora japonica extract, menthol and curcumin are prepared into microcapsule particles by lipid microencapsulation technology; (2) microcapsule particles are mixed with active ingredients such as elderberry extract and β-glucan; (3) Mixing with other excipients and providing at least one excipient. (4) Compress the tablets into tablets, fill the capsules into capsules, or pack the granules into granules.

[0044] Therefore, the compositions provided by the present invention can be discrete units suitable for oral administration, such as capsules or tablets, each of which contains a predetermined amount of one or more active ingredients. These compositions can be prepared by any pharmaceutical method. Generally, such methods include the step of associating the active ingredient with an excipient constituting one or more essential ingredients. Generally, the compositions are prepared by uniformly and closely mixing the active ingredient with a liquid excipient or a finely divided solid excipient or both. The product can then be easily shaped into the desired appearance.

[0045] The microcapsule particles are prepared by the following steps: a. The salvia miltiorrhiza extract, sophora japonica extract, menthol, curcumin and the oil phase solvent were sheared at 5000-20000 r / min at 30-50 ℃ for 5-20min to obtain an oil phase material; b. Add the emulsifier and dispersant to water and shear at 8000-20000 r / min for 10-30 min at 30-50 ° C to obtain an aqueous phase material; c. After mixing the oil phase material and the water phase material to obtain a liquid, shear at 8000-20000 r / min for 15-30 minutes, and then spray dry to obtain microcapsule particles. The spray drying air inlet temperature is 170-200°C, the air outlet temperature is 70-80°C, and the pressure is 15-30 bar.

[0046] The oil phase solvent may include, but is not limited to, one or more of medium chain triglycerides, olive oil, soybean oil, and sesame oil.

[0047] The emulsifier may include, but is not limited to, one or more of sodium starch glycolate, lecithin, sodium lauryl sulfate, Tween 60 or 80, vitamin E polyethylene glycol succinate (TPGS), sorbitan monooleate, polyoxyethylene sorbitan monooleate, poloxamer, polyoxyethylene hydrogenated castor oil, and polyethylene glycol (15)-hydroxystearate.

[0048] The dispersant may include, but is not limited to, one or more of mannitol, lactose, trehalose, and tricalcium phosphate.

[0049] The elderberry-based composition of the present invention utilizes lipid microencapsulation technology to effectively improve the absorption and bioavailability of fat-soluble active ingredients in natural plant extracts, enhancing their effectiveness. It also works synergistically with the elderberry extract. The components of the composition complement and interact with each other to achieve multi-component, multi-target, and multi-pathway effects in preventing and treating lung nodules, including regulating oxidative stress, modulating immunosuppressive inflammatory responses, and regulating signaling pathways associated with epithelial-mesenchymal transition. Anti-tissue inflammation studies have also demonstrated that the present invention exhibits superior efficacy compared to conventional techniques. BRIEF DESCRIPTION OF THE DRAWINGS

[0050] Figure 1 :Changes in inflammatory factor TNF-α levels

[0051] Figure 2 :Changes in the level of inflammatory factor TGF-β1

[0052] Figure 3 :Changes in inflammatory factor IL-1β levels DETAILED DESCRIPTION

[0053] The present invention is further described with reference to the accompanying drawings and examples, but the present invention is not limited to the following examples, etc. It should be noted that in each example, the amount of each component in the prescription is "calculated by weight" unless otherwise specified.

[0054] The sources of the raw materials used in the following examples are as follows: Elderberry extract was purchased from Ningshan Guosheng Biotechnology Co., Ltd. with a specification of 10% anthocyanins; Salvia miltiorrhiza extract was purchased from Ningshan Guosheng Biotechnology Co., Ltd. with the specification of tanshinone IIA 5%; Sophora japonica extract was purchased from Zhejiang Tiancao Biotechnology Co., Ltd. with a specification of 90% quercetin.

[0055] Example 1 name Dosage g Elderberry Extract 25 Salvia miltiorrhiza extract 8 Curcumin 16 Menthol 0.5 β-glucan 10 Sophora japonica extract 14 calcium phosphate 20 Glucose syrup powder 10 microcrystalline cellulose 56 Micro-powder silica gel 0.5 Sodium starch octenylsuccinate 10 Medium-chain triglycerides 60 200 tablets

[0056] This embodiment provides a capsule containing an elderberry composition, the preparation method of which comprises the following steps: (1) curcumin, salvia miltiorrhiza extract, sophora japonica extract, menthol and medium chain triglycerides were sheared at 35° C. and 5000 r / min for 5 min to obtain an oil phase material; (2) adding water to sodium starch octenylsuccinate, tricalcium phosphate, and glucose syrup powder until the solid content is 20%, and shearing at 10,000 r / min for 15 min at 35° C. to obtain an aqueous phase material; (3) The oil phase material and the water phase material were mixed to obtain a liquid, which was sheared at 12,000 r / min for 20 min and then spray-dried to obtain microcapsule particles. The spray drying air inlet temperature was 180°C, the air outlet temperature was 75°C, and the pressure was 20 bar. (4) The microcapsule particles obtained in (3) are mixed with elderberry extract, β-glucan, microcrystalline cellulose, and micropowdered silica gel. (5) Filling capsules with the mixed powder obtained in 4) to obtain elderberry composition capsules.

[0057] Example 2 name Dosage / g Elderberry Extract 20 Curcumin 18 Menthol 0.2 Sophora japonica extract 10 calcium phosphate 20 Glucose syrup powder 10 Mannitol 81.3 Sodium starch octenylsuccinate 10 Medium-chain triglycerides 60 magnesium stearate 0.5 200 bags

[0058] This embodiment provides a capsule containing an elderberry composition, the preparation method of which comprises the following steps: (1) Salvia miltiorrhiza extract, Sophora japonica extract, curcumin, and medium-chain triglycerides were sheared at 8000 rpm for 10 min at 35° C. to obtain an oil phase material; (2) adding sodium starch octenylsuccinate, glucose syrup powder, and calcium phosphate to water, and shearing at 15,000 r / min for 10 min at 35° C. to obtain an aqueous phase material; (3) The oil phase material and the water phase material are mixed to obtain a liquid, which is sheared at 15,000 r / min for 20 min and then spray-dried to obtain microcapsule particles. The spray drying air inlet temperature is 180°C, the air outlet temperature is 75°C, and the pressure is 15 bar; (4) mixing the microcapsule particles obtained in (3) with elderberry extract, β-glucan, mannitol, and magnesium stearate; (5) Filling capsules with the mixed powder obtained in 4) to obtain elderberry composition capsules.

[0059] Example 3

[0060] This embodiment provides a composition tablet containing an elderberry composition, the preparation method of which comprises the following steps: (1) Salvia miltiorrhiza extract, Sophora japonica extract, curcumin, and olive oil were sheared at 50° C. and 10,000 r / min for 20 min to obtain an oil phase material; (2) TPGS and lactose were added to water and sheared at 12,000 rpm for 20 min at 40°C to obtain an aqueous phase material; (3) The oil phase material and the water phase material are mixed to obtain a liquid, which is sheared at 15,000 r / min for 20 min and then spray-dried to obtain microcapsule particles. The spray drying air inlet temperature is 190°C, the air outlet temperature is 80°C, and the pressure is 30 bar; (4) mixing the microcapsule particles obtained in (3) with elderberry extract, β-glucan, microcrystalline cellulose, cross-linked polyvinylpyrrolidone, and magnesium stearate; (5) Compress the product obtained in (4) into tablets to obtain elderberry composition tablets.

[0061] Example 4 name Dosage / g Elderberry Extract 23 Salvia miltiorrhiza extract 6 Curcumin 15 Menthol 0.2 β-glucan 8 Sophora japonica extract 12 calcium phosphate 10 lactose 10 maltodextrin 10 Soy lecithin 8 Medium-chain triglycerides 50 microcrystalline cellulose 66.6 Sodium stearyl fumarate 1.2 200 tablets

[0062] This embodiment provides a composition tablet containing elderberry, and the preparation method thereof comprises the following steps: (1) Salvia miltiorrhiza extract, Sophora japonica extract, curcumin, and medium-chain triglycerides were sheared at 40° C. and 15,000 r / min for 20 min to obtain an oil phase material; (2) adding soy lecithin, lactose, and calcium phosphate to water, and shearing at 18,000 rpm for 20 min at 50° C. to obtain an aqueous phase material; (3) The oil phase material and the water phase material are mixed to obtain a liquid, which is sheared at 15,000 r / min for 20 min and then spray-dried to obtain microcapsule particles. The spray drying air inlet temperature is 185°C, the air outlet temperature is 75°C, and the pressure is 20 bar; (4) mixing the microcapsule particles obtained in 3), elderberry extract, β-glucan, microcrystalline cellulose, maltodextrin and sodium stearyl fumarate; (5) Compress the product obtained in (4) into tablets to obtain elderberry composition tablets.

[0063] Example 5 name Dosage / g Elderberry Extract 27 Salvia miltiorrhiza extract 8 Curcumin 17 Menthol 0.8 β-glucan 12 Sophora japonica extract 16 calcium phosphate 10 Glucose syrup powder 10 Sodium starch octenylsuccinate 10 Medium-chain triglycerides 80 maltodextrin 53 Micro-powder silica gel 2.2 Xanthan gum 2 Aspartame 2 200 bags

[0064] This embodiment provides a granule based on an elderberry composition, the preparation method of which comprises the following steps: (1) Salvia miltiorrhiza extract, Sophora japonica extract, curcumin, and medium-chain triglycerides were sheared at 45° C. and 10,000 r / min for 15 min to obtain an oil phase material; (2) adding sodium starch octenylsuccinate, calcium phosphate, and glucose syrup powder to water, and shearing at 10,000 r / min for 20 min at 45° C. to obtain an aqueous phase material; (3) The oil phase material and the water phase material are mixed to obtain a liquid, which is sheared at 15,000 r / min for 20 min and then spray-dried to obtain microcapsule particles. The spray drying air inlet temperature is 180°C, the air outlet temperature is 75°C, and the pressure is 120 bar; (4) mixing the microcapsule particles obtained in 3), elderberry extract, β-glucan, maltodextrin, xanthan gum, aspartame and micro-powdered silica gel; (5) Packaging the granules to obtain the granules of the composition.

[0065] Comparative Example 1 name Dosage g Elderberry Extract 25 Salvia miltiorrhiza extract 8 Curcumin 16 Menthol 0.5 β-glucan 10 Sophora japonica extract 14 calcium phosphate 20 Glucose syrup powder 10 microcrystalline cellulose 90.5 Pregelatinized starch 5 Micro-powder silica gel 1 200 tablets

[0066] This embodiment provides a capsule containing an elderberry composition, the preparation method of which comprises the following steps: (1) Salvia miltiorrhiza extract, curcumin, Sophora japonica extract, menthol, calcium phosphate, glucose powder and microcrystalline cellulose were mixed, purified water was added, wet granulation was performed, sieved through a 24-mesh sieve, and dried in a hot air circulation oven at 50°C for 4 h until the mixed granules were obtained; (2) mixing the elderberry extract, the mixed particles, and the micro-powdered silica gel; (3) The mixed powder obtained in (2) is filled into capsules to obtain control capsules that are not microencapsulated.

[0067] Example 6 Anti-lung tissue inflammation experiment

[0068] (1) Experimental animals Species: SPF-grade SD rats, male, 9 weeks old, weighing (200 ± 20) g; Number: 36, randomly divided into 6 groups (6 in each group), namely: control group, model group, experimental group 1, experimental group 2, experimental group 3, and comparison group.

[0069] (2) Experimental animal modeling Six rats were fed adaptively for one week, and then weighed one by one. 20% urethane was injected intraperitoneally at a dose of 5 ml / kg. After the rats were anesthetized, bleomycin solution was slowly injected into the model group at a dose of 5 mg / kg using a 1 ml syringe. The control group was injected with an equal amount of 0.9% sodium chloride injection using the same method.

[0070] (3) Experimental period On the third day after the rat model was established, each group was given different drugs for intervention treatment by gavage, with a dose of 200 mg / kg·d, once a day, for 4 weeks.

[0071] Control group: normal diet, and oral administration of normal saline.

[0072] Model group: normal diet, and oral administration of normal saline.

[0073] Experimental group 1: administered with the composition of Example 1,

[0074] Experimental group 2: administered with the composition of Example 2,

[0075] Experimental group 3: administered with the composition of Example 5,

[0076] Control group: administered the composition of Comparative Example 1.

[0077] (4) Detection indicators and methods The cytokine TGF-β1 is an important inflammatory cytokine and is recognized as the most important regulatory factor and initiation hub of tissue fibrosis. TNF-α is a cytokine that induces inflammatory responses, has a chemotactic effect on a variety of inflammatory cells, and induces the production of cytokines, activates and promotes the synthesis and secretion of other inflammatory factors. It is closely related to the formation of granulomas and fibrosis, and is an important and sensitive indicator reflecting the severity of inflammation and tissue damage in the body.

[0078] TGF-β1, TNF-α, and IL-1β cytokines were selected as inflammation-related indicators, and their levels in lung tissues were examined. After 28 days of administration, the rats were killed, the lung tissues were removed, washed with water, dried with filter paper, and weighed. The left lung lobe was fixed in 4% paraformaldehyde and set aside. The right lung was added with physiological saline at a ratio of mass (g): volume (ml) = 1:9, placed on ice for tissue homogenization, and centrifuged at 12000r / min at 4°C for 20 minutes. The supernatant was extracted and the content of TGF-β1, TNF-α, IL-1β, IL-10, and IFN-γ in the lung tissue was detected according to the instructions of the ELISA kit. The absorbance value at a wavelength of 450nm was measured by microplate reader, and the concentration of each cytokine was calculated using the standard curve. The results are shown in Table 1 and Figure 1-3 shown.

[0079] (5) Data Analysis The data were expressed as mean ± standard deviation and compared using one-way analysis of variance (ANOVA) and T test. P < 0.05 was considered significant. The results are shown in Table 1 and Figure 1-3 , where * represents significant difference compared with the model group (P<0.05), and # represents significant difference compared with the control group (P<0.05).

[0080] Table 1 Cytokine detection results of lung tissue of rats in each group (ng / g)

[0081] (6) Results From Table 1 and Figure 1-3 Comparison of the data shows that the levels of TGF-β1, TNF-α, and IL-1β in the lung tissue of the model group rats were significantly higher than those in the normal group. After drug intervention, the levels of TGF-β1, TNF-α, and IL-1β in the lung tissue of rats in each group were reduced to varying degrees compared with the model group, and the differences were statistically significant (P<0.05). This suggests that the experimental group preparations 1-3 and the control group all have different degrees of anti-inflammatory effects, reducing the inflammatory response of lung nodules, thereby treating lung nodules. Among them, the experimental group has the strongest effect. This further illustrates that the composition based on elderberry extract prepared by the lipid microencapsulation technology of the present invention has more significant effects than conventional technology.

[0082] The present invention can better inhibit inflammatory factors and reduce the inflammatory response of lung nodules. The examples show that the present invention can play a better role in preventing, treating and eliminating lung nodules.

Claims

1. A composition based on elderberry, characterized in that The invention is composed of elderberry extract, salvia miltiorrhiza extract, sophora japonica extract, curcumin, menthol and beta-glucan. The weight ratio of the components is 20-30:4-10:10-18:14-18:0.1-1:5-15.

2. The composition according to claim 1, characterized in that The proportions of the components, namely, elderberry extract, salvia miltiorrhiza extract, sophora japonica flower extract, curcumin, menthol and beta-glucan, are 23-27:6-8:12-16:15-17:0.2-0.8:8-12, in parts by weight.

3. Use of the composition according to claim 1 or 2 in preparing a drug for eliminating pulmonary nodules.

4. The use according to claim 3, characterized in that The medicine is prepared from the composition and pharmaceutically acceptable excipients.

5. The use according to claim 3, characterized in that The drug is prepared by the following method: (1) Salvia miltiorrhiza extract, Sophora japonica extract, menthol and curcumin are prepared into microcapsule particles by lipid microencapsulation technology; (2) microcapsule particles are mixed with elderberry extract and β-glucan active ingredients; (3) mixing with excipients; (4) Compress the tablets into tablets, fill the capsules into capsules, or pack the granules into granules.

6. The use according to claim 3, characterized in that The microcapsule particles are prepared by the following steps: a. The salvia miltiorrhiza extract, sophora japonica extract, menthol, curcumin and the oil phase solvent were sheared at 5000-20000 r / min at 30-50 ℃ for 5-20min to obtain an oil phase material; b. Add the emulsifier and dispersant to water and shear at 8000-20000 r / min for 10-30 min at 30-50 ° C to obtain an aqueous phase material; c. After mixing the oil phase material and the aqueous phase material to obtain a liquid, the liquid is sheared at 8000-20000 r / min for 15-30 min, and then spray-dried to obtain microcapsule particles. The air inlet temperature of the spray drying is 170-200°C, the air outlet temperature is 70-80°C, and the pressure is 15-30 bar.

7. The use according to claim 6, characterized in that The oil phase solvent is selected from one or more of medium chain triglycerides, olive oil, soybean oil or sesame oil.

8. The use according to claim 6, characterized in that The emulsifier is selected from one or more of sodium starch octenylsuccinate, lecithin, sodium lauryl sulfate, Tween 60 or 80, vitamin E polyethylene glycol succinate, sorbitol monooleate, polyoxyethylene sorbitan monooleate, poloxamer, polyoxyethylene hydrogenated castor oil or polyethylene glycol (15)-hydroxystearate.

9. The use according to claim 6, characterized in that The dispersant is selected from one or more of mannitol, lactose, trehalose or tricalcium phosphate.

10. The use according to claim 3, characterized in that The pharmaceutical dosage form is an oral preparation, which is selected from soft capsules, capsules, tablets, granules, suspensions or emulsions.

Images