A pharmaceutical composition for improving immunity and a preparation method thereof

Abstract

The present application relates to the technical field of pharmaceutical compositions, and discloses a kind of pharmaceutical compositions for improving immunity and preparation method thereof, comprising: echinacea extract, lactoferrin peptide, seleniumized carrageenan, yeast beta-glucan, glutathione, lentinan, natural cordyceps militaris fruit body powder, fructooligosaccharide or galactooligosaccharide, vitamin D3, zinc citric acid, pretreatment, mixing, intermittent ultrasonic dispersion, low-temperature forming and spray drying are made into, wherein with the amount of echinacea extension, other synergistic components are adjusted in proportion, maintain the balance of immune activation-antioxidation-mucosa protection.The pharmaceutical composition disclosed in the present application is flexible in dosage, has synergistic effect of multiple components, has significant immunoregulatory effect, is high in safety and stable in process.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical composition technology, and more specifically, to a pharmaceutical composition for enhancing immunity and its preparation method. Background Technology

[0002] Immunity, as the core defense system of the human body against the invasion of exogenous pathogens and the elimination of abnormal cells in the body, encompasses two major dimensions: innate immunity and acquired immunity. Whether its function is normal or not directly determines the health status of the body. Innate immunity responds quickly to pathogens through macrophages and natural killer cells, while acquired immunity depends on the proliferation and differentiation of T / B lymphocytes to form specific antibodies. The two work together to maintain the stability of the internal environment.

[0003] In recent years, the number of people with weakened immune systems has continued to expand, with the causes becoming increasingly diverse: long-term mental stress caused by a fast-paced lifestyle and irregular sleep patterns can inhibit the secretion of immune cytokines; in the process of population aging, the immune organ function of the elderly naturally declines, with thymus atrophy and decreased spleen hematopoietic capacity, leading to a significant reduction in the number and activity of immune cells; environmental pollution and increased pathogen mutation further weaken the body's immune barrier; in addition, medical factors such as chronic diseases (e.g., diabetes, chronic kidney disease), radiotherapy and chemotherapy, long-term use of immunosuppressants, as well as unhealthy lifestyle habits such as smoking, excessive drinking, and lack of exercise, can all directly disrupt immune homeostasis, leading to a series of health risks such as recurrent infections and a high incidence of tumors.

[0004] Current immunomodulatory drugs on the market have many limitations: most products have a single ingredient, or rely solely on plant polysaccharides (such as lentinan), or focus on a single immune target (such as activating only cellular immunity), resulting in a one-sided mechanism of action and difficulty in achieving multi-dimensional synergistic regulation; some chemically synthesized immunomodulators, although they have a relatively fast onset of action, are prone to causing side effects such as gastrointestinal discomfort, increased burden on liver and kidney function, and allergic reactions, and their long-term safety is insufficient; at the same time, the dosage of existing drugs is fixed, which cannot adapt to the personalized needs of different scenarios such as mild immunodeficiency (such as sub-healthy people) and severe immunodeficiency (such as patients after radiotherapy and chemotherapy), resulting in insufficient flexibility in clinical application.

[0005] Therefore, developing a novel, synergistic, and safe immune-boosting drug composition is of great practical significance. Summary of the Invention

[0006] In view of this, the present invention proposes a pharmaceutical composition for enhancing immunity and its preparation method. The components of the pharmaceutical composition are synergistic and complementary, with significant immunomodulatory effects and a simple preparation process. The present invention also provides its preparation method and application, aiming to solve the problems of single components, poor synergy, limited safety, and insufficient dosage suitability of immunomodulatory drugs in the current technology.

[0007] This invention provides a pharmaceutical composition for enhancing immunity, comprising the following components in parts by weight: Echinacea extract 100-150 parts, lactoferrin peptide 3-9 parts, selenized carrageenan 1-3 parts, yeast β-glucan 1-6 parts, glutathione 0.5-2.25 parts, lentinan 40-60 parts, natural Cordyceps militaris fruiting body powder 60-83 parts, fructooligosaccharide or galactooligosaccharide 40-65 parts, vitamin D3 0.5-2.5 parts, zinc citric acid 1-3 parts.

[0008] Furthermore, the echinacea extract is prepared by ultrasound-assisted ethanol extraction of echinacea at an extraction temperature of 45-55°C; the content of chicoric acid in the echinacea extract is 3-10%.

[0009] Furthermore, the molecular weight distribution of the lactoferrin peptide is 1000~3000 Da.

[0010] Furthermore, the method for preparing the immune-enhancing pharmaceutical composition includes the following steps: (1) Pretreatment: Echinacea extract, lentinan, and natural Cordyceps militaris fruiting body powder were passed through a 100-mesh sieve and set aside. (2) Mixed phase A: Add lactoferrin peptide, selenized carrageenan, yeast β-glucan and glutathione to deionized water, stir to dissolve, and obtain mixed phase A; (3) Mixed Phase B: The sieved echinacea extract, lentinan, natural cordyceps fruiting body powder, fructooligosaccharide or galactooligosaccharide are mixed to obtain mixed phase B; (4) Composite dispersion: The mixed phase A is slowly added to the mixed phase B while intermittent ultrasonic dispersion is performed to obtain a mixture. (5) Low temperature molding: Add vitamin D3 and zinc citric acid to the mixture, stir evenly, refrigerate at low temperature and then spray dry to obtain the finished drug composition.

[0011] Furthermore, the stirring parameters in step (2) are: rotation speed 500~800r / min, temperature 30~40℃; the amount of deionized water added is 3~5 times the total mass of lactoferrin peptide, selenized carrageenan, yeast β-glucan and glutathione.

[0012] Furthermore, the mixing in step (3) is a dry mix for 15-25 minutes.

[0013] Furthermore, the intermittent ultrasonic dispersion parameters in step (4) are: power 200~300W, frequency 20~40kHz, dispersion time 20~30min.

[0014] Furthermore, the refrigeration parameters in step (5) are: temperature -5~0℃, time 1~2h.

[0015] Furthermore, the spray drying parameters in step (5) are: inlet air temperature 160~180℃, outlet air temperature 70~80℃, feed rate 20~30mL / min, and atomization pressure 0.3~0.5MPa.

[0016] This invention also protects the use of the above-mentioned pharmaceutical composition, specifically in the preparation of oral immunomodulatory agents and drugs for improving immunodeficiency after radiotherapy and chemotherapy.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows: By combining multiple active ingredients such as echinacea extract, lactoferrin peptide, and selenized carrageenan, this product synergistically enhances immunity through multiple pathways, including immune cell activation, antioxidant protection, and gut microbiota regulation, thus overcoming the limitations of single-ingredient effects.

[0018] The dosage of each component in this invention has been strictly optimized to avoid poor effects due to insufficient dosage or side effects caused by excessive dosage, thus ensuring high safety.

[0019] This invention employs an ultrasonic-assisted dispersion and low-temperature molding process, which effectively preserves the activity of the heat-sensitive active ingredients, improves the uniformity and stability of the composition, and effectively ensures the efficacy of the drug composition.

[0020] The pharmaceutical composition prepared by this invention can be used to prepare oral immunomodulatory agents, which are especially suitable for improving the immunity of people with weakened immunity after radiotherapy and chemotherapy, and have important clinical application value.

[0021] The pharmaceutical composition prepared by this invention has multiple components that synergistically complement each other, have a comprehensive pathway of action, high safety, and flexible dosage adjustment to improve immunity. It has important clinical value and practical significance for meeting the health needs of different immunocompromised populations and filling market gaps. Detailed Implementation

[0022] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention. It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the present invention.

[0023] Furthermore, regarding the numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Every smaller range between any stated value or intermediate value within a stated range, and any other stated value or intermediate value within said range, is also included within this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0024] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0025] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0026] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0027] Unless otherwise specified, "parts" in this invention refer to parts by mass. In the following examples, the raw materials are weighed according to 1 part = 1g.

[0028] This invention provides a pharmaceutical composition for enhancing immunity, the pharmaceutical composition comprising the following components in parts by weight: Echinacea extract 100-150 parts, lactoferrin peptide 3-9 parts, selenized carrageenan 1-3 parts, yeast β-glucan 1-6 parts, glutathione 0.5-2.25 parts, lentinan 40-60 parts, natural Cordyceps militaris fruiting body powder 60-83 parts, fructooligosaccharide or galactooligosaccharide 40-65 parts, vitamin D3 0.5-2.5 parts, zinc citric acid 1-3 parts.

[0029] In this invention, the pharmaceutical composition is further preferably composed of the following components in parts by weight: Echinacea extract 120-150 parts, lactoferrin peptide 3.6-9 parts, selenized carrageenan 1.2-3 parts, yeast β-glucan 1.2-6 parts, glutathione 0.6-2.25 parts, lentinan 45-60 parts, natural Cordyceps militaris fruiting body powder 65-83 parts, fructooligosaccharides or galactooligosaccharides 40-65 parts, vitamin D3 1-2.5 parts, zinc citric acid 1.5-3 parts.

[0030] In this invention, the echinacea extract is prepared by ultrasound-assisted ethanol extraction of echinacea, with the extraction temperature preferably being 45-55°C, more preferably 48-55°C; the chicoric acid content in the echinacea extract is preferably 3-10%, more preferably 3-7%.

[0031] In this invention, the molecular weight distribution of the lactoferrin peptide is 1000~3000 Da.

[0032] This invention adds echinacea extract to the immune-enhancing pharmaceutical composition. The echinacea extract contains chicoric acid and polyphenols that can activate macrophages and lymphocytes, enhance the phagocytic ability of immune cells, and also activate immune cells such as macrophages and natural killer cells, thereby improving the body's defense against viruses and bacteria. Furthermore, the echinacea extract works by regulating immune cell activity and inhibiting pathogen proliferation. The specified dosage range ensures the effective concentration of the core active ingredient; reducing the dosage weakens the immune-activating effect, while increasing it may lead to ingredient waste and potential irritation. The selected dosage range of the echinacea extract ensures the effective concentration of the core active ingredient; reducing the dosage weakens the immune-activating effect, while increasing it may lead to ingredient waste and potential irritation.

[0033] This invention adds lactoferrin peptide to the aforementioned immune-enhancing pharmaceutical composition. As a natural active protein, lactoferrin peptide participates in various physiological processes such as immune regulation and antimicrobial activity. It can competitively bind to iron ions, depriving harmful bacteria of their "nutrient source" and inhibiting their reproduction. It can also activate immune cells such as macrophages and lymphocytes, regulating the balance between innate and adaptive immunity, and building a dual immune defense for the body. The lactoferrin peptide is a small molecule peptide with a molecular weight of 1000-3000 Da, easily absorbed by the human body, and can regulate the secretion of immune cytokines and promote lymphocyte proliferation. Furthermore, after echinacea activates immune cells, adding the lactoferrin peptide can regulate cytokine secretion, avoiding incomplete immune activation. Regarding the dosage of the lactoferrin peptide, insufficient dosage will not achieve an effective blood concentration, resulting in weak immune regulation; excessive dosage may cause intestinal flora imbalance and significantly increase costs.

[0034] This invention adds selenized carrageenan to the immune-enhancing pharmaceutical composition. Selenized carrageenan is an organic selenium donor that synergistically combats oxidation with glutathione. The organic selenium compounds in the selenized carrageenan allow selenium to participate in the synthesis of glutathione peroxidase, enhancing the body's antioxidant capacity and protecting immune cells from damage. During the preparation process, the increased use of echinacea is accompanied by mild oxidative stress, necessitating a simultaneous increase in selenium supply to protect immune cells. Regarding the dosage of selenized carrageenan, insufficient dosage will result in inadequate antioxidant activity and failure to effectively protect immune cells, while excessive selenium may lead to poisoning, causing adverse reactions such as nausea and vomiting.

[0035] This invention adds yeast β-glucan to the immune-enhancing pharmaceutical composition. Yeast β-glucan is a polysaccharide extracted from yeast cell walls, so there is no need to worry about side effects. It can be supplemented during seasonal changes to enhance immunity, stimulate the intestinal mucosal immune system, promote immunoglobulin secretion, and enhance mucosal barrier function. It can also stimulate the body's immune cells (macrophages, neutrophils, etc.), enhancing the body's immune response. When echinacea enhances systemic immunity, it is necessary to simultaneously strengthen the mucosal barrier to avoid immune imbalance. Regarding the dosage of yeast β-glucan, insufficient dosage will lead to insufficient activation of mucosal immunity, while excessive dosage can easily cause intestinal bloating and affect the user experience.

[0036] This invention adds glutathione to the pharmaceutical composition for enhancing immunity. Glutathione is a naturally occurring antioxidant in the human body that can neutralize free radicals, reduce oxidative stress damage to cells, and indirectly enhance immunity by regulating oxidative stress and supporting immune cell function. Immune cells produce a large number of free radicals when fighting pathogens, and excessive oxidative stress may inhibit immune function. Glutathione can also scavenge free radicals in the body, reduce oxidative stress damage to immune cells, and synergistically enhance the antioxidant effect with selenized carrageenan. Furthermore, glutathione indirectly supports the normal functioning of the immune system by protecting immune cells from oxidative damage. Regarding the dosage of glutathione, insufficient dosage results in an insignificant synergistic antioxidant effect, while excessive dosage increases its instability and makes it prone to decomposition and inactivation.

[0037] This invention adds lentinan to the immune-enhancing pharmaceutical composition. Lentinan is a natural immunomodulator that can bind to specific receptors on the surface of immune cells, activate T lymphocytes and B lymphocytes, improve humoral and cellular immunity, enhance phagocytic capacity, increase the efficiency of pathogen clearance, increase antibody production, strengthen humoral and cellular immunity, and balance pro-inflammatory and anti-inflammatory factors, reducing excessive inflammatory responses. Regarding the dosage of lentinan, insufficient dosage will result in insufficient immune cell activation, while excessive dosage may lead to over-activation of the immune system and trigger an inflammatory response.

[0038] This invention adds natural Cordyceps militaris fruiting body powder to the immune-enhancing pharmaceutical composition. The Cordyceps militaris fruiting body powder contains cordycepic acid, cordycepin, and other components, which can improve the function of immune organs and promote the proliferation and differentiation of immune cells. It also contains abundant polysaccharides, proteins, amino acids, and other nutrients, which can effectively improve human immunity and enhance resistance. The polysaccharides in the Cordyceps militaris fruiting body powder have anti-fatigue effects, which can improve human endurance, relieve fatigue, and improve work efficiency. The polyphenolic compounds in the Cordyceps militaris fruiting body powder have strong antioxidant effects, which can scavenge free radicals in the body, delay aging, and protect cells. Regarding the dosage of the Cordyceps militaris fruiting body powder, insufficient dosage may result in ineffective immune organ protection, while excessive dosage may cause antagonism between its components, reducing the overall immune regulation effect.

[0039] The present invention adds fructooligosaccharides or galactooligosaccharides to the pharmaceutical composition for enhancing immunity. The fructooligosaccharides or galactooligosaccharides can promote the proliferation of beneficial bacteria in the intestine, regulate the balance of intestinal microecology, and indirectly enhance immunity. Regarding the selection of the amount of fructooligosaccharides or galactooligosaccharides, if the amount is insufficient, the effect of beneficial bacteria proliferation will be poor, and if the amount is excessive, it may lead to an imbalance of intestinal osmotic pressure and cause diarrhea.

[0040] The present invention adds vitamin D3 to the pharmaceutical composition for enhancing immunity. Vitamin D3 supports the immune system by regulating calcium and phosphorus balance and promoting immune cell function. It can activate immune cells, help identify and fight pathogens, regulate inflammatory responses, and regulate the expression of immune cell surface receptors, thereby enhancing the ability of immune cells to recognize pathogens. Regarding the dosage of vitamin D3, insufficient dosage and excessive dosage will lead to insufficient receptor regulation and may lead to calcium metabolism disorders, respectively.

[0041] The present invention adds zinc citric acid to the pharmaceutical composition for enhancing immunity. Zinc citric acid promotes growth and development and enhances immunity. Its zinc element participates in the synthesis and activity regulation of immune enzymes and promotes the development and maturation of immune cells. Regarding the dosage of zinc citric acid, insufficient dosage will lead to insufficient immune enzyme activity, while excessive dosage will lead to calcium metabolism disorders and affect the absorption of minerals such as iron and copper.

[0042] In this invention, the method for preparing the immune-enhancing pharmaceutical composition includes the following steps: (1) Pretreatment: Echinacea extract, lentinan, and natural Cordyceps militaris fruiting body powder were passed through a 100-mesh sieve and set aside. (2) Mixed phase A: Add lactoferrin peptide, selenized carrageenan, yeast β-glucan and glutathione to deionized water, stir to dissolve, and obtain mixed phase A; (3) Mixed Phase B: The sieved echinacea extract, lentinan, natural cordyceps fruiting body powder, fructooligosaccharide or galactooligosaccharide are mixed to obtain mixed phase B; (4) Composite dispersion: The mixed phase A is slowly added to the mixed phase B while intermittent ultrasonic dispersion is performed to obtain a mixture. (5) Low temperature molding: Add vitamin D3 and zinc citric acid to the mixture, stir evenly, refrigerate at low temperature and then spray dry to obtain the finished drug composition.

[0043] In this invention, the stirring parameters in step (2) are preferably: rotation speed 500~800 r / min, temperature 30~40℃, and more preferably: rotation speed 600~800 r / min, temperature 33~40℃; the amount of deionized water added is preferably 3~5 times the total mass of lactoferrin peptide, selenized carrageenan, yeast β-glucan and glutathione, and more preferably 3~4 times.

[0044] In this invention, the mixing in step (3) is preferably dry mixing for 15 to 25 minutes, and more preferably dry mixing for 18 to 25 minutes.

[0045] In this invention, the intermittent ultrasonic dispersion in step (4) is a 30-second working and 10-second pause. The ultrasonic dispersion parameters are preferably: power 200-300W, frequency 20-40kHz, dispersion time 20-30min, and more preferably: power 220-300W, frequency 25-40kHz, dispersion time 25-30min.

[0046] In this invention, the refrigeration parameters in step (5) are preferably: temperature -5~0℃ and time 1~2h, and more preferably: temperature -3~0℃ and time 1.5~2h.

[0047] In this invention, the spray drying parameters in step (5) are preferably: inlet air temperature 160~180℃, outlet air temperature 70~80℃, feed rate 20~30mL / min, and atomization pressure 0.3~0.5MPa, and more preferably: inlet air temperature 165~180℃, outlet air temperature 73~80℃, feed rate 22~30mL / min, and atomization pressure 0.4~0.5MPa.

[0048] This invention also protects the use of the above-mentioned pharmaceutical composition, specifically in the preparation of oral immunomodulatory agents and drugs for improving immunodeficiency after radiotherapy and chemotherapy.

[0049] In this invention, unless otherwise specified, all raw materials required for preparation are commercially available products well known to those skilled in the art.

[0050] The technical solutions provided by the present invention will be 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.

[0051] Example 1 The raw material components are: 120 parts of Echinacea extract (chicoric acid content 3%), 3.6 parts of lactoferrin peptide, 1.2 parts of selenized carrageenan, 1.2 parts of yeast β-glucan, 0.6 parts of glutathione, 45 parts of lentinan, 65 parts of natural Cordyceps militaris fruiting body powder, 40 parts of fructooligosaccharides, 1 part of vitamin D3, and 1.5 parts of zinc citric acid.

[0052] Preparation method: (1) Pretreatment: Echinacea extract, lentinan, and natural Cordyceps militaris fruiting body powder were passed through a 100-mesh sieve and set aside. (2) Mixed phase A: Add lactoferrin peptide, selenized carrageenan, yeast β-glucan and glutathione to 3 times the total mass of raw material components in deionized water, and stir to dissolve at 33℃ and 600 r / min to obtain mixed phase A; (3) Mixed phase B: The sieved echinacea extract, lentinan, natural cordyceps fruiting body powder and oligofructose were dry-mixed for 18 min to obtain mixed phase B; (4) Composite dispersion: The mixed phase A is slowly added to the mixed phase B, and the mixture is subjected to intermittent ultrasonic dispersion for 30 minutes with a working power of 220W and a frequency of 25kHz, followed by a pause of 10s, to obtain the mixture. (5) Low temperature molding: Add vitamin D3 and zinc citric acid to the mixture, stir evenly, refrigerate at -3℃ for 1.5h, and then spray dry under the conditions of inlet air temperature of 165℃, outlet air temperature of 73℃, feed rate of 22mL / min and atomization pressure of 0.4MPa to obtain the finished drug composition.

[0053] Example 2 The raw material components are: 130 parts of Echinacea extract (5% chicoric acid), 5 parts of lactoferrin peptide, 1.5 parts of selenized carrageenan, 3 parts of yeast β-glucan, 1 part of glutathione, 50 parts of lentinan, 70 parts of natural Cordyceps militaris fruiting body powder, 50 parts of galactooligosaccharide, 1.5 parts of vitamin D3, and 2 parts of zinc citric acid.

[0054] Preparation method: (1) Pretreatment: Echinacea extract, lentinan, and natural Cordyceps militaris fruiting body powder were passed through a 100-mesh sieve and set aside. (2) Mixed phase A: Add lactoferrin peptide, selenized carrageenan, yeast β-glucan and glutathione to 3 times the total mass of raw material components in deionized water, and stir to dissolve at 36℃ and 700 r / min to obtain mixed phase A; (3) Mixed phase B: The sieved echinacea extract, lentinan, natural cordyceps fruiting body powder and galactooligosaccharide were dry-mixed for 20 min to obtain mixed phase B; (4) Composite dispersion: The mixed phase A is slowly added to the mixed phase B, and at the same time, intermittent ultrasonic dispersion is carried out for 28 minutes with an ultrasonic dispersion power of 250W and a frequency of 30kHz, with a working time of 30s and a pause of 10s, to obtain the mixture. (5) Low temperature molding: Add vitamin D3 and zinc citric acid to the mixture, stir evenly, refrigerate at -3℃ for 1.5h, and then spray dry under the conditions of inlet air temperature of 170℃, outlet air temperature of 75℃, feed rate of 25mL / min and atomization pressure of 0.4MPa to obtain the finished drug composition.

[0055] Example 3 The raw material components are: 150 parts of Echinacea extract (7% chicoric acid), 9 parts of lactoferrin peptide, 3 parts of selenized carrageenan, 6 parts of yeast β-glucan, 2.25 parts of glutathione, 60 parts of lentinan, 83 parts of natural Cordyceps militaris fruiting body powder, 65 parts of fructooligosaccharides, 2.5 parts of vitamin D3, and 3 parts of zinc citric acid.

[0056] Preparation method: (1) Pretreatment: Echinacea extract, lentinan, and natural Cordyceps militaris fruiting body powder were passed through a 100-mesh sieve and set aside. (2) Mixed phase A: Add lactoferrin peptide, selenized carrageenan, yeast β-glucan and glutathione to 4 times the total mass of raw material components in deionized water, and stir to dissolve at 40℃ and 800 r / min to obtain mixed phase A; (3) Mixed phase B: The sieved echinacea extract, lentinan, natural cordyceps fruiting body powder and oligofructose were dry-mixed for 25 min to obtain mixed phase B; (4) Composite dispersion: The mixed phase A is slowly added to the mixed phase B, and at the same time, intermittent ultrasonic dispersion is carried out for 25 minutes with an ultrasonic dispersion power of 300W and a frequency of 40kHz, with a working time of 30s and a pause of 10s, to obtain the mixture. (5) Low temperature molding: Add vitamin D3 and zinc citric acid to the mixture, stir evenly, refrigerate at 0°C for 2 hours, and then spray dry under the conditions of inlet air temperature of 180°C, outlet air temperature of 80°C, feed rate of 30mL / min and atomization pressure of 0.5MPa to obtain the finished drug composition.

[0057] Comparative Example 1 Components: 150 parts of Echinacea extract (7% chicoric acid), 3 parts of selenized carrageenan, 6 parts of yeast β-glucan, 2.25 parts of glutathione, 60 parts of lentinan, 83 parts of natural Cordyceps militaris fruiting body powder, 65 parts of fructooligosaccharides, 2.5 parts of vitamin D3, 3 parts of zinc citric acid, and 4.5 parts of lactoferrin peptide. Compared with Example 3, the amount of lactoferrin peptide is less.

[0058] Preparation method: Same as in Example 3.

[0059] Comparative Example 2 Raw materials: 130 parts of Echinacea extract (5% chicoric acid content), 5 parts of lactoferrin peptide, 1.5 parts of selenized carrageenan, 3 parts of yeast β-glucan, 1 part of glutathione, 50 parts of lentinan, 90 parts of natural Cordyceps militaris fruiting body powder, 50 parts of galactooligosaccharide, 1.5 parts of vitamin D3, and 2 parts of zinc citric acid. Compared with Example 2, the amount of natural Cordyceps militaris fruiting body powder is increased and exceeds the dosage range of this invention.

[0060] Preparation method: Same as in Example 2.

[0061] Comparative Example 3 Raw material composition: 120 parts of Echinacea extract (chicoric acid content 3%), 3.6 parts of lactoferrin peptide, 1.2 parts of selenized carrageenan, 1.2 parts of yeast β-glucan, 0.6 parts of glutathione, 45 parts of lentinan, 65 parts of natural Cordyceps militaris fruiting body powder, 70 parts of fructooligosaccharides, 1 part of vitamin D3, and 1.5 parts of zinc citric acid. Compared with Example 1, the amount of fructooligosaccharides is increased and exceeds the range of the present invention. Preparation method: Same as in Example 1.

[0062] Performance testing: (1) The thymus index (mg / g) was detected by the immune organ weight and index determination method. Immune organ index (mg / g) = organ wet weight (mg) / mouse body weight (g). The test was based on GB / T 15670.26-2019 "Toxicological Test Methods for Pesticide Registration Part 26: Immune Function Test".

[0063] (2) The spleen index (mg / g) was detected by the immune organ weight and index determination method. Immune organ index (mg / g) = organ wet weight (mg) / mouse body weight (g). The test was based on GB / T 15670.26-2019 "Toxicological Test Methods for Pesticide Registration Part 26: Immune Function Test".

[0064] (3) The lymphocyte transformation rate (%) was measured by the MTT assay. The lymphocyte transformation rate (%) = (OD value of experimental group - OD value of blank well) / OD value of blank well × 100%, where OD value is absorbance. The test was conducted according to WS / T 802-2022 "Lymphocyte Transformation Test MTT Method" and GB / T 15670.26-2019 "Toxicological Test Methods for Pesticide Registration Part 26: Immunological Function Test".

[0065] (4) The detection of serum IgG content (mg / mL) was performed by enzyme-linked immunosorbent assay (ELISA). The detection was based on GB / T 15670.26-2019 "Toxicological Test Methods for Pesticide Registration Part 26: Immunological Function Tests" and GB / T 27403-2008 "Laboratory Quality Control Standards for Microbiological Testing of Food" (General Operating Requirements for ELISA).

[0066] (5) The incidence of intestinal bloating (%) was detected by the observation method of apparent signs of experimental animals. The detection was based on GB / T 39476-2020 "Standardized Management of Laboratory Animals Mice and Rats" and GB / T 15670.26-2019 "Toxicological Test Methods for Pesticide Registration Part 26: Immunological Function Test" (Requirements for Apparent Observation of Drug Toxicity).

[0067] One hundred and forty SPF-grade Kunming mice were randomly divided into a blank control group, Example 1-3 groups, and Comparative Example 1-3 groups, with 20 mice in each group. Except for the blank control group, the other groups were administered the drug by gavage at a dose of 100 mg / (kg·d) for 30 consecutive days. The performance of the drug compositions described in Examples 1-3 and Comparative Example 1-3 on the mice is shown in Table 1 below (results are expressed as mean ± standard deviation): Table 1 Performance test results of the pharmaceutical compositions described in Examples 1-3 and Comparative Examples 1-3 In summary, in Examples 1-3, as the dosage of Echinacea and the content of chicoric acid increased, the immune indicators (thymus index, spleen index, etc.) showed a steady upward trend, and the incidence of intestinal bloating was controlled within 7%, verifying the scientific validity of dosage expansion and component synergy. In Comparative Examples 1-3, insufficient or excessive use of lactoferrin peptide / Cordyceps militaris fruiting body powder / fructooligosaccharides led to incomplete activation of immune cells, resulting not only in a decrease in immune indicators but also a surge in the incidence of intestinal bloating. In contrast, the pharmaceutical composition described in this invention has a wider range of raw material sources, higher safety, avoids cost waste and side effects, and allows for adaptive addition of raw materials according to the needs of people with different levels of immunodeficiency, resulting in high production efficiency and good uniformity and stability of the finished product.

[0068] The above embodiments are merely preferred embodiments of the present invention and are not intended to limit the present invention. The scope of protection of the present invention is determined by the appended claims.

[0069] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the specific implementation of the present invention. Any modifications or equivalent substitutions that do not depart from the spirit and scope of the present invention should be covered within the scope of protection of the claims of the present invention.

Claims

1. A pharmaceutical composition for enhancing immunity, characterized in that, The components include the following parts by mass: Echinacea extract 100-150 parts, lactoferrin peptide 3-9 parts, selenized carrageenan 1-3 parts, yeast β-glucan 1-6 parts, glutathione 0.5-2.25 parts, lentinan 40-60 parts, natural Cordyceps militaris fruiting body powder 60-83 parts, fructooligosaccharide or galactooligosaccharide 40-65 parts, vitamin D3 0.5-2.5 parts, zinc citric acid 1-3 parts.

2. The pharmaceutical composition for enhancing immunity according to claim 1, characterized in that, The echinacea extract is prepared by ultrasound-assisted ethanol extraction of echinacea at an extraction temperature of 45-55℃; the content of chicoric acid in the echinacea extract is 3-10%.

3. The pharmaceutical composition for enhancing immunity according to claim 1, characterized in that, The molecular weight distribution of the lactoferrin peptide is 1000~3000 Da.

4. The method for preparing a pharmaceutical composition for enhancing immunity according to claim 1, characterized in that, Includes the following steps: (1) Pretreatment: Echinacea extract, lentinan, and natural Cordyceps militaris fruiting body powder were passed through a 100-mesh sieve and set aside. (2) Mixed phase A: Add lactoferrin peptide, selenized carrageenan, yeast β-glucan and glutathione to deionized water, stir to dissolve, and obtain mixed phase A; (3) Mixed Phase B: The sieved echinacea extract, lentinan, natural cordyceps fruiting body powder, fructooligosaccharide or galactooligosaccharide are mixed to obtain mixed phase B; (4) Composite dispersion: The mixed phase A is slowly added to the mixed phase B while intermittent ultrasonic dispersion is performed to obtain a mixture. (5) Low temperature molding: Add vitamin D3 and zinc citric acid to the mixture, stir evenly, refrigerate at low temperature and then spray dry to obtain the finished drug composition.

5. The method for preparing a pharmaceutical composition for enhancing immunity according to claim 4, characterized in that, The stirring parameters in step (2) are: rotation speed 500~800 r / min, temperature 30~40℃; the amount of deionized water added is 3~5 times the total mass of lactoferrin peptide, selenized carrageenan, yeast β-glucan and glutathione.

6. The method for preparing a pharmaceutical composition for enhancing immunity according to claim 4, characterized in that, The mixing in step (3) is a dry mix for 15-25 minutes.

7. The method for preparing a pharmaceutical composition for enhancing immunity according to claim 4, characterized in that, The intermittent ultrasonic dispersion parameters mentioned in step (4) are: power 200~300W, frequency 20~40kHz, dispersion time 20~30min.

8. The method for preparing a pharmaceutical composition for enhancing immunity according to claim 4, characterized in that, The refrigeration parameters in step (5) are: temperature -5~0℃, time 1~2h.

9. The method for preparing a pharmaceutical composition for enhancing immunity according to claim 4, characterized in that, The spray drying parameters in step (5) are: inlet air temperature 160~180℃, outlet air temperature 70~80℃, feed rate 20~30mL / min, and atomization pressure 0.3~0.5MPa.

10. An application of the pharmaceutical composition according to any one of claims 1 to 3, wherein the application is specifically in the preparation of oral immunomodulatory agents and drugs for improving immunodeficiency after radiotherapy and chemotherapy.

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