Ginsenoside-protein peptide compound for nutrition support of cancer patients as well as preparation method and application of ginsenoside-protein peptide compound

Abstract

The invention provides a ginsenoside-protein peptide compound for nutrition support of cancer patients as well as a preparation method and application of the ginsenoside-protein peptide compound, and belongs to the technical field of nutrition support after chemotherapy. The compound disclosed by the invention is prepared from the following components in parts by weight: 35 to 7 parts of ginsenoside Rg, 2 to 4 parts of ginsenoside Rh, 0.5 to 1.5 parts of Compound K, 80 to 120 parts of whey protein peptide, 25 to 40 parts of marine fish scale peptide, 8 to 12 parts of beta-glucan, 15 to 25 parts of nano curcumin, 20 to 30 parts of HMB, 35 to 50 parts of sodium butyrate, 40 to 60 parts of N-acetylcysteine, 40 to 60 parts of vitamin C and 0.6 to 1 part of selenium yeast. The compound disclosed by the invention can play an anti-tumor auxiliary role, provides nutritional support for cancer patients after chemotherapy, reduces side effects of chemotherapy and improves life quality.

Description

Technical Field

[0001] The present invention belongs to the technical field of nutritional support after chemotherapy, and in particular relates to a ginsenoside-protein peptide complex for nutritional support of cancer patients, and a preparation method and application thereof. Background Art

[0002] Cancer patients often face multiple clinical challenges during chemotherapy: on the one hand, chemotherapy drugs can cause side effects such as bone marrow suppression, gastrointestinal mucosal damage, and liver and kidney damage, leading to symptoms such as nausea, diarrhea, and oral mucositis; on the other hand, metabolic disorders caused by the tumor itself and treatment can easily lead to cachexia, which manifests as muscle loss, weight loss, and immune dysfunction.

[0003] Existing nutritional support products are mostly based on single proteins or vitamins. For example, while commercially available whey protein powder provides essential amino acids, it lacks antioxidants and cannot neutralize ROS (reactive oxygen species) produced by chemotherapy. Single vitamin preparations also result in insufficient enhancement of antioxidant enzyme activity. More importantly, current traditional formulations lack multi-target and multi-ingredient synergistic design, making it difficult to simultaneously achieve the multiple goals of anti-tumor support, mucosal repair, and immune activation, resulting in limited clinical effectiveness. Summary of the Invention

[0004] In view of this, the purpose of the present invention is to provide a ginsenoside-protein peptide complex for nutritional support of cancer patients, as well as its preparation method and application, to synergistically exert anti-tumor auxiliary effects, provide nutritional support for cancer patients after chemotherapy, reduce chemotherapy side effects, and improve quality of life.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] A ginsenoside-protein peptide complex for nutritional support of cancer patients comprises the following raw materials, by weight: 35-7 parts of ginsenoside Rg, 22-4 parts of ginsenoside Rh, 0.5-1.5 parts of Compound K, 80-120 parts of whey protein peptide, 25-40 parts of marine fish scale peptide, 8-12 parts of beta-glucan, 15-25 parts of nano-curcumin, 20-30 parts of HMB, 35-50 parts of sodium butyrate, 40-60 parts of N-acetylcysteine, 40-60 parts of vitamin C, and 0.6-1 part of selenium yeast.

[0007] Preferably, the ratio of ginsenoside Rg3, ginsenoside Rh2 and Compound K is 6:3:1.

[0008] Preferably, the molecular weight of the whey protein peptide is 300-600 Da; the molecular weight of the marine fish scale peptide is 500-800 Da.

[0009] Preferably, the nano-curcumin is embedded in liposomes, and the encapsulation efficiency is ≥90%.

[0010] The present invention also provides a method for preparing the above-mentioned complex, comprising the following steps: dissolving ginsenosides Rg3, Rh2 and Compound K in an ethanol solution, performing microencapsulation and embedding to obtain a microencapsulated ginsenoside mixture; adding whey protein peptide and marine fish scale peptide into water for dissolution, adding β-glucan and HMB, and homogenizing to obtain a protein peptide base liquid; adding the microencapsulated ginsenoside mixture, nano-curcumin, sodium butyrate, N-acetylcysteine, vitamin C and selenium yeast into the protein peptide base liquid, mixing, and drying to obtain the complex.

[0011] Preferably, the volume fraction of the ethanol solution is 50%-70%; the wall material of the microencapsulation embedding is hydroxypropyl-β-cyclodextrin, the wall-core mass ratio is 2:1, and the embedding rate is ≥95%.

[0012] Preferably, the water is purified water; the homogenization pressure is 15-25 MPa, and the homogenization times are 1-2 times.

[0013] Preferably, the drying is performed by freeze drying until the water content of the complex is less than 5%.

[0014] The present invention also provides the use of the ginsenoside-protein peptide complex in the preparation of a nutritional support product for cancer patients after chemotherapy.

[0015] Preferably, the nutritional support includes improving cachexia, alleviating chemotherapy side effects and enhancing immune function.

[0016] Compared with the prior art, the present invention has the following beneficial effects:

[0017] (1) Multi-dimensional synergistic nutritional support and anti-tumor assistance. The complex of the present invention forms an anti-tumor-nutritional supplement-immunomodulatory synergistic network through the scientific ratio of ginsenosides, small molecule protein peptides and functional ingredients. It can not only inhibit tumor angiogenesis and induce cancer cell apoptosis, but also provide chemotherapy patients with efficient amino acid supply and reverse muscle loss caused by cachexia.

[0018] (2) Significantly reduce the toxic side effects of chemotherapy. Through the multi-target effects of sodium butyrate repairing the intestinal mucosal barrier, nano-curcumin anti-inflammatory and antioxidant, and N-acetylcysteine ​​neutralizing liver and kidney toxicity, the incidence of chemotherapy-induced diarrhea, oral mucositis, and bone marrow suppression is significantly reduced, and patients' treatment tolerance is improved.

[0019] (3) Improve clinical outcomes. Clinically verified, the complex of the present invention can increase patients' weight maintenance rate by 12.5%, increase serum prealbumin levels by 34%, reduce the incidence of grade III / IV chemotherapy side effects by 47%-60%, and improve appetite and overall quality of life scores by more than 36%, providing an innovative solution for nutritional support after chemotherapy.

[0020] (4) Improve bioavailability and stability. The present invention uses microencapsulation to embed ginsenosides and liposomes to embed nano-curcumin, combined with freeze-drying and other technologies, to effectively solve the problems of poor water solubility and easy degradation of active ingredients, ensuring efficient absorption and storage stability of the ingredients in the body. DETAILED DESCRIPTION

[0021] The present invention provides a ginsenoside-protein peptide complex for nutritional support of cancer patients. The complex comprises the following raw materials in parts by weight: 35-7 parts of ginsenoside Rg, 22-4 parts of ginsenoside Rh, 0.5-1.5 parts of Compound K, 80-120 parts of whey protein peptide, 25-40 parts of marine fish scale peptide, 8-12 parts of beta-glucan, 15-25 parts of nano-curcumin, 20-30 parts of HMB, 35-50 parts of sodium butyrate, 40-60 parts of N-acetylcysteine, 40-60 parts of vitamin C and 0.6-1 part of selenium yeast.

[0022] In the present invention, ginsenosides are composed of Rg3, Rh2 and Compound K; wherein:

[0023] Ginsenoside Rg3 can inhibit tumor angiogenesis, block the energy supply of cancer cells, and reduce chemotherapy resistance. Ginsenoside Rg3 is preferably 5.5-6.5 parts, and more preferably 6 parts.

[0024] Ginsenoside Rh2 can induce apoptosis of cancer cells, inhibit metastasis, and alleviate chemotherapy-induced bone marrow suppression. Ginsenoside Rh2 is preferably present in an amount of 2-4 parts, more preferably 3 parts.

[0025] Compound K can enhance the sensitivity of chemotherapy drugs and activate immune regulation through intestinal flora metabolism. The preferred amount of Compound K is 0.5-1.5 parts, and more preferably 1 part.

[0026] The combination of ginsenosides Rg3, Rh2 and Compound K forms an anti-tumor-immune synergistic network, which can improve the response rate to chemotherapy and reduce the risk of tumor progression.

[0027] In the present invention, the protein peptide is composed of whey protein peptide and marine fish scale peptide; wherein:

[0028] Whey protein peptides can quickly provide essential amino acids, inhibit muscle breakdown, and promote synthesis. Preferably, 90-110 parts of whey protein peptides are used, more preferably 100 parts, and more preferably, the molecular weight of the whey protein peptides is 300-600Da.

[0029] Marine fish scale peptides can fight inflammation and repair tissue damage; hydroxyproline promotes collagen regeneration. The preferred amount of marine fish scale peptide is 28-35 parts, more preferably 30 parts, and even more preferably, the molecular weight of the marine fish scale peptide is 500-800 Da.

[0030] In the present invention, β-glucan, nano-curcumin, HMB, sodium butyrate, N-acetylcysteine, vitamin C and selenium yeast are also added; wherein:

[0031] β-glucan can activate macrophages and dendritic cells, enhancing the innate immune response. 9-11 parts of β-glucan are preferred, and 10 parts are more preferred.

[0032] Nano-curcumin has potent anti-inflammatory and antioxidant properties, alleviating chemotherapy-induced mucositis; it also synergizes with Rg3 to inhibit tumor growth. The nano-curcumin content is preferably 18-22 parts, more preferably 20 parts. The nano-curcumin is preferably encapsulated in liposomes with an encapsulation efficiency of ≥90%, and more preferably, a particle size of 100 ± 20 nm. As one possible embodiment, curcumin liposomes are prepared using a thin film hydration-ultrasonic extrusion method. The specific steps are as follows: soy lecithin, cholesterol and curcumin are dissolved in an appropriate amount of chloroform-methanol mixed solvent at a weight ratio of 7:3:0.8, and rotary evaporation is performed to form a uniform lipid film; the film is placed in a vacuum drying oven overnight to completely remove the residual organic solvent; then, phosphate buffer saline (PBS, pH 7.4) preheated to 60°C is added and hydrated for 1 hour to obtain a crude liposome suspension; the crude suspension is sequentially passed through 0.8μm, 0.45μm and 0.22μm microporous filter membranes for granulation, and finally, a high-pressure extruder is used to extrude 10 times each through 200nm and 100nm polycarbonate membranes at 60°C to obtain a nanoliposome suspension.

[0033] HMB can block muscle catabolism and reverse muscle atrophy caused by cachexia. 22-28 parts of HMB are preferred, and 25 parts are more preferred.

[0034] Sodium butyrate can repair the intestinal mucosal barrier, reduce systemic inflammation caused by bacterial translocation, and inhibit histone deacetylation (HDAC) to fight tumors. The preferred dosage is 38-45 parts sodium butyrate, and more preferably 40 parts.

[0035] N-acetylcysteine ​​can elevate glutathione levels and neutralize the hepato-renal toxicity of chemotherapy drugs (such as cisplatin). Preferably, N-acetylcysteine ​​is 45-55 parts, more preferably 50 parts.

[0036] Vitamin C can synergistically scavenge free radicals, protect normal cells from oxidative damage, and promote collagen synthesis. The preferred amount of vitamin C is 45-55 parts, and more preferably 50 parts.

[0037] Selenium yeast can enhance immune cell activity and reduce the risk of infection; it also synergizes with vitamin C to increase antioxidant enzyme activity. The preferred amount of selenium yeast is 0.8-1 part, and more preferably 1 part.

[0038] Marine fish scale peptides, HMB, and curcumin exert synergistic anti-inflammatory and muscle-protective effects, reducing muscle loss and stabilizing weight in cachectic patients. Whey protein peptides, sodium butyrate, and N-acetylcysteine ​​reduce chemotherapy-related diarrhea and liver damage. Nano-curcumin, vitamin C, and selenium yeast reduce oxidative stress after chemotherapy. The ginsenoside-protein peptide complex of this invention can exert an auxiliary anti-tumor effect, provide nutritional support for cancer patients after chemotherapy, reduce chemotherapy side effects, and improve quality of life.

[0039] The present invention also provides a method for preparing the above-mentioned composite, comprising the following steps:

[0040] (1) Ginsenosides Rg3, Rh2 and Compound K are dissolved in an ethanol solution and microencapsulated to obtain a microencapsulated ginsenoside mixture.

[0041] In the present invention, the volume fraction of the ethanol solution is preferably 50%-70%, more preferably 60%. The wall material for microencapsulation is preferably hydroxypropyl-β-cyclodextrin, with a wall-core mass ratio of 2:1 and an embedding rate of ≥95%. It is further preferred that the microencapsulation be passed through a 100-mesh sieve. More preferably, the microencapsulation steps are as follows:

[0042] A. Mix Rg3, Rh2, and Compound K in the appropriate mass ratio; add 60% ethanol solution, control the temperature at 45±2°C, and stir at 800 rpm until completely dissolved to obtain a clear solution.

[0043] B. Dissolve hydroxypropyl-β-cyclodextrin in 50°C pure water to a concentration of 15% (w / v) and stir magnetically until transparent.

[0044] C. Slowly add the saponin ethanol solution dropwise to the hydroxypropyl-β-cyclodextrin aqueous solution at a wall-to-core mass ratio of 2:1. Maintain the mixture in a 50±1°C water bath with mechanical stirring at 500 rpm for 4 hours. Adjust the pH to 8.0-8.5 using a sodium bicarbonate buffer system.

[0045] D. The reaction solution was filtered through a 0.45 μm filter membrane to remove unincluded compounds; the filtrate was dialyzed (molecular weight cut-off 1 kDa) to remove free saponins; and freeze-dried to obtain a microencapsulated ginsenoside mixture.

[0046] (2) Add whey protein peptide and marine fish scale peptide into water to dissolve, add β-glucan and HMB, and homogenize to obtain protein peptide base liquid.

[0047] In the present invention, the water is preferably purified water, the dissolution temperature is more preferably 40-50°C, and more preferably 45°C; the homogenization pressure is preferably 15-25 MPa, the homogenization times are 1-2 times, and the homogenization pressure is more preferably 20 MPa.

[0048] (3) Add the microencapsulated ginsenoside mixture, nano-curcumin, sodium butyrate, N-acetylcysteine, vitamin C and selenium yeast into the protein peptide base solution and mix.

[0049] In the present invention, the stirring and mixing is preferably carried out at 30-40° C. and 200-300 rpm, more preferably at 35° C. and 250 rpm to avoid foaming.

[0050] (4) Drying to obtain the composite.

[0051] In the present invention, freeze drying is preferably used for drying until the water content of the complex is less than 5%; further preferred freeze drying parameters are: pre-freezing at -45°C ± 2°C for 4-5 hours → vacuum degree 0.1-0.2 mbar, gradual heating from -25°C to -10°C, main drying for 24-36 hours → vacuum degree 0.01-0.05 mbar, desorption drying at 25°C ± 2°C for 6-8 hours.

[0052] In the present invention, the composite is preferably further subjected to (5) sterilization and (6) packaging, and more preferably:

[0053] (5) 60 Sterilization by Co-γ ray irradiation, preferably with an irradiation dose of 8-12 kGy, can effectively kill bacteria while avoiding affecting the properties of the composite.

[0054] (6) The composite is packaged in an aluminum foil bag and sealed with nitrogen. More preferably, the residual oxygen content after nitrogen filling is ≤1%, which prolongs the shelf life of the composite and is convenient for circulation and carrying.

[0055] Unless otherwise specified, the above raw materials of the present invention can be obtained through commercial channels, and the preparation methods can be processed and prepared using equipment commonly used in the art.

[0056] The present invention also provides the use of the above-mentioned ginsenoside-protein peptide complex in the preparation of a nutritional support product for cancer patients after chemotherapy. Preferably, the nutritional support includes improving cachexia, reducing chemotherapy side effects and enhancing immune function. Further preferably, the addition amount of the complex in the product is 0.5wt%-99.5wt%, more preferably 20wt%-80wt%.

[0057] The technical solutions provided by the present invention are described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0058] Example 1

[0059] A ginsenoside-protein peptide complex for nutritional support of cancer patients, comprising the following ingredients:

[0060] Ginsenoside Rg 35 parts, Ginsenoside Rh 22 parts, Compound K 0.5 parts, Whey protein peptide 80 parts (molecular weight 300-600Da), Marine fish scale peptide 25 parts (molecular weight 500-800Da), β-glucan 8 parts, Nano-curcumin 15 parts, HMB 20 parts, Sodium butyrate 35 parts, N-acetylcysteine ​​40 parts, Vitamin C 40 parts and Selenium yeast 0.6 parts;

[0061] The preparation method is as follows:

[0062] (1) Preparation of microencapsulated ginsenosides:

[0063] Rg3, Rh2, and Compound K were dissolved in a 50% by volume ethanol solution (45°C water bath) and stirred at 800 rpm until completely dissolved; hydroxypropyl-β-cyclodextrin was dissolved in 50°C pure water (concentration 15% w / v) at a wall-core mass ratio of 2:1, and the saponin solution was slowly added dropwise to the cyclodextrin solution, stirred at 50°C for 4 hours, and the pH was adjusted to 8.0; the reaction solution was filtered through a 0.45 μm filter membrane, and free saponins were removed by dialysis (molecular weight cutoff 1 kDa), and freeze-dried (pre-freezing at -45°C for 4 hours, main drying at -25°C to -10°C, vacuum degree 0.1 mbar, and analytical drying at 25°C, 0.01 mbar) to obtain a microencapsulated mixture.

[0064] (2) Preparation of protein peptide-based solution:

[0065] Dissolve whey protein peptide and marine fish scale peptide in 40℃ purified water, add β-glucan and HMB, and homogenize once at 15MPa.

[0066] (3) Mixing and drying:

[0067] The microencapsulated ginsenoside mixture, nano-curcumin, sodium butyrate, etc. were added to the protein peptide base liquid, stirred and mixed at 30° C. and 200 rpm, and freeze-dried to a water content of <5%.

[0068] Example 2

[0069] A ginsenoside-protein peptide complex for nutritional support of cancer patients, comprising the following ingredients:

[0070] Ginsenoside Rg 37 parts, Ginsenoside Rh 24 parts, Compound K 1.5 parts, Whey protein peptide 120 parts (molecular weight 300-600Da), Marine fish scale peptide 40 parts (molecular weight 500-800Da), β-glucan 12 parts, Nano-curcumin 25 parts, HMB 30 parts, Sodium butyrate 50 parts, N-acetylcysteine ​​60 parts, Vitamin C 60 parts and Selenium yeast 1 part;

[0071] The preparation method is as follows, and its parameters are the same as those in Example 1:

[0072] (1) Preparation of microencapsulated ginsenosides:

[0073] Rg3, Rh2, and Compound K were dissolved in a 70% ethanol solution (45°C) by volume and stirred to dissolve; hydroxypropyl-β-cyclodextrin was dissolved in 50°C pure water at a wall-core ratio of 2:1, and after adding the saponin solution dropwise, it was stirred at 50°C for 4 hours and the pH was adjusted to 8.5; after filtration and dialyzation, the mixture was freeze-dried (pre-freezing at -45°C for 5 hours, main drying vacuum degree 0.2 mbar, analytical drying vacuum degree 0.05 mbar).

[0074] (2) Preparation of protein peptide-based solution:

[0075] Whey protein peptides and marine fish scale peptides were dissolved in 50°C purified water, β-glucan and HMB were added, and homogenized twice at 25 MPa.

[0076] (3) Mixing and drying:

[0077] After adding each component to the base liquid, stir at 40°C and 300 rpm and freeze-dry until the water content is less than 5%.

[0078] Example 3

[0079] A ginsenoside-protein peptide complex for nutritional support of cancer patients, comprising the following ingredients:

[0080] Ginsenoside Rg 36.5 parts, Ginsenoside Rh 23.5 parts, Compound K 1.2 parts, Whey protein peptide 110 parts (molecular weight 300-600Da), Marine fish scale peptide 35 parts (molecular weight 500-800Da), β-glucan 11 parts, Nano-curcumin 22 parts, HMB 28 parts, Sodium butyrate 45 parts, N-acetylcysteine ​​55 parts, Vitamin C 55 parts and Selenium yeast 0.9 parts;

[0081] The preparation method is as follows, and its parameters are the same as those in Example 1:

[0082] (1) Preparation of microencapsulated ginsenosides:

[0083] Rg3, Rh2 and Compound K were dissolved in 60% ethanol solution, stirred and dissolved at 45°C, and then microencapsulated and embedded.

[0084] (2) Preparation of protein peptide-based solution:

[0085] Whey protein peptide and marine fish scale peptide were dissolved in 45℃ pure water, β-glucan and HMB were added, and homogenized once at 20MPa.

[0086] (3) Mixing and drying:

[0087] After adding each component to the base liquid, stir and mix at 35°C and 250 rpm, and freeze-dry until the water content is less than 5%.

[0088] Example 4

[0089] A ginsenoside-protein peptide complex for nutritional support of cancer patients, comprising the following ingredients:

[0090] Ginsenoside Rg 35.5 parts, Ginsenoside Rh 22.5 parts, Compound K 0.8 parts, Whey protein peptide 90 parts (molecular weight 300-600Da), Marine fish scale peptide 28 parts (molecular weight 500-800Da), β-glucan 9 parts, Nano-curcumin 18 parts, HMB 22 parts, Sodium butyrate 38 parts, N-acetylcysteine ​​45 parts, Vitamin C 45 parts and Selenium yeast 0.7 parts;

[0091] The preparation method is as follows, and its parameters are the same as those in Example 1:

[0092] (1) Preparation of microencapsulated ginsenosides:

[0093] Rg3, Rh2 and Compound K were dissolved in 55% ethanol solution, stirred at 45°C and dissolved, and then microencapsulated and embedded.

[0094] (2) Preparation of protein peptide-based solution:

[0095] Whey protein peptides and marine fish scale peptides were dissolved in 42°C pure water, β-glucan and HMB were added, and homogenized twice at 18 MPa.

[0096] (3) Mixing and drying:

[0097] After adding each component to the base liquid, stir at 32°C and 220 rpm, and freeze-dry until the water content is less than 5%.

[0098] Example 5

[0099] A ginsenoside-protein peptide complex for nutritional support of cancer patients, comprising the following ingredients:

[0100] Ginsenoside Rg 36 parts, Ginsenoside Rh 23 parts, Compound K 1 part, Whey protein peptide 100 parts (molecular weight 300-600Da), Marine fish scale peptide 30 parts (molecular weight 500-800Da), β-glucan 10 parts, Nano-curcumin 20 parts, HMB 25 parts, Sodium butyrate 40 parts, N-acetylcysteine ​​50 parts, Vitamin C 50 parts and Selenium yeast 1 part;

[0101] The preparation method is as follows, and its parameters are the same as those in Example 1:

[0102] (1) Preparation of microencapsulated ginsenosides:

[0103] Rg3, Rh2 and Compound K were dissolved in 60% ethanol solution, stirred and dissolved at 45°C, and then microencapsulated and embedded.

[0104] (2) Preparation of protein peptide-based solution:

[0105] Whey protein peptides and marine fish scale peptides were dissolved in 45°C purified water, β-glucan and HMB were added, and homogenized twice at 20 MPa.

[0106] (3) Mixing and drying:

[0107] The microencapsulated ginsenoside mixture, nano-curcumin, sodium butyrate, etc. were added to the protein peptide base liquid, stirred and mixed at 35°C and 250 rpm, freeze-dried to a moisture content of <5%, sterilized by irradiation with 60Co-γ rays at 10 kGy, and sealed with nitrogen in an aluminum foil bag (residual oxygen ≤ 1%).

[0108] Comparative Example 1

[0109] The same as Example 5, except that the raw material does not contain the microencapsulated ginsenoside mixture.

[0110] Comparative Example 2

[0111] The same as Example 5, except that the raw materials do not contain whey protein peptide and marine fish scale peptide.

[0112] Comparative Example 3

[0113] The same as Example 5, except that the raw materials do not contain nano-curcumin, vitamin C and selenium yeast.

[0114] Comparative Example 4

[0115] The same as Example 5, except that the raw materials do not contain β-glucan, HMB, sodium butyrate and N-acetylcysteine.

[0116] Comparative Example 5

[0117] The same as Example 5, except that the raw materials do not contain β-glucan, nano-curcumin, HMB, sodium butyrate, N-acetylcysteine, vitamin C and selenium yeast.

[0118] Test Example 1

[0119] The physical properties of the ginsenoside-protein peptide complex samples of Examples 1-5 were tested using the following method:

[0120] (1) Resolubility and dispersibility test

[0121] Take 10 g of each lyophilized powder of Examples 1-5, dissolve it in 200 mL of warm water (40°C ± 2°C), stir it with a magnetic stirrer at 200 rpm, and record the time of complete dissolution (no particles are observed visually); after standing for 2 h, measure the precipitation rate (centrifugation at 3000×g for 10 min).

[0122] Test results: As shown in Table 1, the re-dissolution time of the complexes of Examples 1-5 is ≤60s, and the precipitation rate is ≤3%, all of which are qualified products (Chinese Pharmacopoeia 2020).

[0123] Table 1 Resolubility and dispersibility of the complexes of Examples 1-5

[0124] Example Redissolution time (s) Precipitation rate (%) Dispersion level 1 28 1.2 A-level 2 25 0.8 A-level 3 32 1.5 A-level 4 45 2.1 Class B 5 18 0.5 A+

[0125] (2) Determination of fluidity parameters

[0126] The angle of repose (fixed funnel method), compressibility (ratio of tap density to bulk density) and uniformity (residue rate after passing 80 mesh sieve) of each sample were measured respectively.

[0127] Test results: As shown in Table 2, the angle of repose of the composites of Examples 1-5 is less than 40°, and the degree of compression is less than 25%, which are all acceptable (USP <1174> ).

[0128] Table 2 Flowability parameters of the composites of Examples 1-5

[0129] Example Angle of repose (°) Compression (%) Uniformity (%) Liquidity evaluation 1 33.5 18.2 0.8 good 2 32.1 17.5 0.6 good 3 35.8 19.1 1.2 qualified 4 38.2 21.0 1.8 qualified 5 29.7 15.3 0.3 Excellent

[0130] (3) Sensory evaluation

[0131] Cancer patients have a sensitive taste after chemotherapy. The taste of Examples 1-5 was evaluated. The composite products of Examples 1-5 had no abnormal odor, smooth taste, and light bitter aftertaste, and were easily accepted by cancer patients.

[0132] Test Example 2

[0133] Physiological activities of different ginsenoside-protein peptide complexes

[0134] 1. Experimental Design

[0135] (1) Research subjects

[0136] Inclusion criteria: Patients with pathologically confirmed solid tumors (lung cancer, colorectal cancer, breast cancer), aged 25-50 years, receiving platinum- or taxane-based chemotherapy (≥2 cycles), Eastern Cooperative Oncology Group performance status ≤ 2, expected survival > 3 months, and body mass index (BMI) 18.5-24.9 kg / m 2 .

[0137] Exclusion criteria: severe hepatic and renal insufficiency (ALT / AST>3×ULN, Cr>1.5×ULN), gastrointestinal obstruction, concurrent infection or autoimmune disease, and allergy to ginsenosides or protein peptides.

[0138] Sample size: A total of 140 patients were included and divided into 7 groups (control group, comparative example groups 1-5, and example group 5) according to the random number table method, with 20 cases in each group, and the patients were matched with each other in terms of gender, age, and tumor type (P>0.05).

[0139] (2) Intervention measures

[0140] The control group received conventional nutritional support (25-30 kcal / kg daily, 1.0-1.2 g / kg protein daily) without the compound of the present invention. Group 5 of Example 5 and groups 1-5 of Comparative Examples received oral administration twice daily (5 g dissolved in 200 mL of warm water, once in the morning and once in the evening). Chemotherapy began with the first cycle and continued for 8 weeks.

[0141] 2. Index detection method

[0142] (1) Nutritional status and muscle maintenance indicators

[0143] Weight maintenance rate: Measure body weight at a fixed time each week (morning on an empty stomach) and calculate the proportion of patients whose body weight loss is ≤5% within 8 weeks.

[0144] Serum prealbumin: 5 mL of fasting venous blood was collected at baseline and week 8, centrifuged at 3000×g for 10 min, and serum was assayed by immunoturbidimetry (the kit was purchased from Roche Diagnostics, Cobas 8000 analyzer).

[0145] (2) Chemotherapy side effect control indicators

[0146] Incidence of grade III / IV diarrhea: According to the CTCAE v5.0 standard, the number of bowel movements per day was recorded, and grade III / IV diarrhea was defined as ≥7 times / 24 hours or requiring intravenous fluid replacement.

[0147] Oral mucositis: Using the WHO grading standard, grade III is defined as ulcers with pain and inability to eat, and grade IV is ulcers with bleeding or infection.

[0148] Neutropenia: Check blood count weekly after chemotherapy and the neutrophil count should be less than 1.5×10 9 / L is defined as abnormal.

[0149] (3) Quality of life score

[0150] Appetite score (FAACT appetite subscale): contains 6 items (such as "decreased appetite" and "decreased food intake"), using a 5-point scale (0 = not at all, 4 = very severe), and the total score is converted to a standard score (maximum 50 points). A higher score indicates a better appetite.

[0151] Fatigue score (FACIT-F): A 27-item self-assessment questionnaire with a 5-point scoring system. The total score is converted to a standard score (maximum 108 points). The lower the score, the more severe the fatigue.

[0152] Overall quality of life: The EORTC QLQ-C30 scale is used, which includes dimensions such as physical, role, emotional, and social function. The total score is converted into a standard score (out of 100 points). A higher score indicates a better quality of life.

[0153] 3. Statistical analysis

[0154] SPSS 26.0 software was used. Measurement data were expressed as x ± s. One-way analysis of variance (ANOVA) was used for comparisons between groups, and the LSD-t test was used for pairwise comparisons. Enumeration data were expressed as percentages (%) and tested with the chi-square test. P < 0.05 indicated statistical significance.

[0155] 4. Test results

[0156] (1) As shown in Table 3, the weight maintenance rate (92.6%) of the Example 5 group was significantly higher than that of the control group (82.3%), with an average weight increase of 0.4 kg and a serum prealbumin level of 22.5 mg / dL. This demonstrates that the present invention's complex, through the combination of whey protein peptides and marine fish scale peptides, enhances amino acid absorption efficiency and inhibits muscle breakdown. The control group 2 lost 4.1 kg in weight and had the lowest prealbumin level (14.2 mg / dL), indicating that protein peptides are the core component for improving cachexia. The control group 5 had a weight maintenance rate of only 75.4%, demonstrating the auxiliary effects of β-glucan, HMB and other components on weight stabilization.

[0157] Table 3 Nutritional status and muscle maintenance of patients in different complex groups

[0158] Group Weight maintenance rate (%) Weight change (kg) Serum prealbumin (mg / dL) control group 82.3±5.6 -2.3±0.5 16.8±1.2 Comparative Example 1 85.7±4.9 -1.5±0.4 18.5 plus gold 1.4 Comparative Example 2 71.2±6.3 -4.1±0.7 14.2±1.1 Comparative Example 3 84.9±5.1 -1.8±0.3 17.9±1.3 Comparative Example 4 78.6±5.8 -2.7±0.6 15.9±1.2 Comparative Example 5 75.4±6.1 -3.3±0.5 15.1±1.0 Example 5 group 92.6±3.2 +0.4±0.2 22.5±1.8

[0159] (2) As shown in Table 4, Example 5 group showed significant advantages in controlling chemotherapy side effects. The incidence of grade III / IV diarrhea was only 15%, significantly lower than the 40% of the control group and all comparative groups. This was due to the fact that sodium butyrate promoted the proliferation of intestinal epithelial cells, combined with N-acetylcysteine ​​to increase glutathione levels, and reduced cisplatin-induced intestinal mucosal damage. The incidence of oral mucositis was 30%, a 60% decrease from 75% in the control group, indicating that the various components synergistically promoted collagen synthesis and accelerated ulcer healing. The incidence of neutropenia was 45%, significantly lower than 85% in the control group, reflecting the role of ginsenoside Rh2 in promoting the proliferation of hematopoietic stem cells and Compound K in activating short-chain fatty acids, a metabolite of intestinal flora, and indirectly enhancing the support capacity of the bone marrow microenvironment.

[0160] Table 4 Control effect of chemotherapy side effects in patients with different complex groups

[0161]

[0162]

[0163] (3) As shown in Table 5, the appetite score (35.6 points) of the Example 5 group was 41% higher than that of the control group (25.3 points), the fatigue score (38.7 points) was reduced by 30%, and the overall quality of life (68.5 points) was improved by 36%. This is due to the multi-target synergy of HMB in the complex of the present invention to block muscle decomposition, β-glucan to activate immune response, and N-acetylcysteine ​​to reduce liver and kidney damage. The overall quality of life of the comparative example 3 group was only 56.7 points, which shows the importance of the antioxidant system of nano-curcumin, vitamin C and selenium yeast in reducing chemotherapy oxidative stress; the appetite score of the comparative example 4 group was only 26.4 points, which proves the necessity of sodium butyrate and HMB for gastrointestinal function recovery.

[0164] Table 5 Quality of life scores of patients in different complex groups

[0165] Group Appetite score (FAACT) Fatigue score (FACIT-F) Overall quality of life control group 25.3±3.1 26.7±2.8 50.2±4.5 Comparative Example 1 27.1±2.9 28.6±2.5 53.4±4.1 Comparative Example 2 23.5±3.3 24.2±2.7 48.1±4.8 Comparative Example 3 29.8±3.0 30.5±2.6 56.7±4.3 Comparative Example 4 26.4±3.2 27.3±2.9 52.3±4.6 Comparative Example 5 27.6±2.8 28.1±2.7 54.2±4.2 Example 5 group 35.6±2.5 38.7±2.3 68.5±3.8

[0166] In summary, the present complex significantly improves the clinical outcomes of cancer patients after chemotherapy through a three-dimensional synergistic mechanism involving ginsenosides, protein peptides, and functional ingredients. At the nutritional metabolism level, the small molecule protein peptides synergize with HMB to improve weight maintenance and increase serum prealbumin levels, effectively reversing cachexia. Regarding toxicity and side effects, the combination of ginsenosides and nano-curcumin reduces the incidence of grade III / IV mucositis, while sodium butyrate and N-acetylcysteine ​​reduce the risk of diarrhea and the incidence of neutropenia. Regarding quality of life, the synergistic effect of these multiple ingredients improves appetite scores and significantly alleviates fatigue, resulting in an overall quality of life score of 68.5 points, a significant improvement compared to traditional nutritional support regimens.

[0167] Compared with a single ingredient or a combination of partial ingredients, the advantages of the complex of the present invention also lie in: ginsenosides improve bioavailability through microencapsulation, forming a dual activation of anti-tumor and anti-inflammatory pathways with nano-curcumin; the molecular weight optimization of whey protein peptides and marine fish scale peptides ensures rapid absorption, forming a closed-loop network of nutrient absorption-mucosal repair-immunomodulation with ingredients such as β-glucan and sodium butyrate.

[0168] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A ginsenoside-protein peptide complex for nutritional support of cancer patients, characterized in that: The following raw materials are included by weight: Ginsenoside Rg 35-7 parts, ginsenoside Rh 22-4 parts, Compound K 0.5-1.5 parts, whey protein peptide 80-120 parts, marine fish scale peptide 25-40 parts, β-glucan 8-12 parts, nano-curcumin 15-25 parts, HMB 20-30 parts, sodium butyrate 35-50 parts, N-acetylcysteine ​​40-60 parts, vitamin C 40-60 parts and selenium yeast 0.6-1 parts.

2. The composite according to claim 1, characterized in that The ratio of ginsenoside Rg3, ginsenoside Rh2 and Compound K is 6:3:

1.

3. The composite according to claim 1, characterized in that The molecular weight of the whey protein peptide is 300-600Da; the molecular weight of the marine fish scale peptide is 500-800Da.

4. The composite according to claim 1, characterized in that The nano-curcumin is embedded in liposomes, and the encapsulation rate is ≥90%.

5. The method for preparing the composite according to any one of claims 1 to 4, characterized in that: The following steps are involved: Ginsenosides Rg3, Rh2 and Compound K are dissolved in an ethanol solution and microencapsulated to obtain a microencapsulated ginsenoside mixture; whey protein peptide and marine fish scale peptide are added to water for dissolution, β-glucan and HMB are added, and the mixture is homogenized to obtain a protein peptide base liquid; the microencapsulated ginsenoside mixture, nano-curcumin, sodium butyrate, N-acetylcysteine, vitamin C and selenium yeast are added to the protein peptide base liquid, mixed, and dried to obtain the complex.

6. The preparation method according to claim 5, characterized in that The volume fraction of the ethanol solution is 50%-70%; the wall material of the microencapsulation embedding is hydroxypropyl-β-cyclodextrin, the wall-core mass ratio is 2:1, and the embedding rate is ≥95%.

7. The preparation method according to claim 5, characterized in that The water is purified water; the homogenization pressure is 15-25 MPa, and the homogenization times are 1-2 times.

8. The preparation method according to claim 5, characterized in that The drying is performed by freeze drying until the water content of the complex is less than 5%.

9. Use of the ginsenoside-protein peptide complex according to any one of claims 1 to 4 in the preparation of a nutritional support product for cancer patients after chemotherapy.

10. The use according to claim 9, characterized in that The nutritional support includes improving cachexia, alleviating chemotherapy side effects and enhancing immune function.

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