A ginsenoside-protein peptide complex for cancer patient nutritional support, and a preparation method and application thereof

Abstract

The present application provides a ginsenoside-protein peptide complex for nutritional support of cancer patients, and a preparation method and application thereof, and belongs to the technical field of post-chemotherapy nutritional support.The present application comprises ginsenoside Rg3 5-7 parts, ginsenoside Rh2 2-4 parts, Compound K 0.5-1.5 parts, whey protein peptide 80-120 parts, marine fish scale peptide 25-40 parts, beta-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 part by weight.The present application can play an anti-tumor auxiliary role, provide nutritional support for cancer patients after chemotherapy, reduce the side effects of chemotherapy, and improve the quality of life.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of post-chemotherapy nutritional support, and particularly relates to a ginsenoside-protein peptide complex for nutritional support of cancer patients, and a preparation method and application thereof. BACKGROUND

[0002] Cancer patients often face multiple clinical challenges during chemotherapy: on the one hand, chemotherapy drugs can cause bone marrow suppression, gastrointestinal mucosa damage, liver and kidney function damage and other side effects, resulting in symptoms such as nausea, diarrhea, oral mucositis; on the other hand, metabolic disorders caused by tumors and treatment can easily lead to cachexia, manifested as muscle loss, weight loss and immune function decline.

[0003] Existing nutritional support products are mainly single protein or vitamins, for example, although whey protein powder on the market can provide essential amino acids, it lacks antioxidant components and cannot neutralize ROS (reactive oxygen species) produced during chemotherapy; single vitamin preparations cannot sufficiently improve antioxidant enzyme activity. More importantly, current traditional formulations lack multi-target synergistic design and multi-component synergistic design, making it difficult to simultaneously achieve the multiple goals of anti-tumor adjuvant, mucosa repair and immune activation, resulting in limited clinical application effect. SUMMARY

[0004] Therefore, the present application aims to provide a ginsenoside-protein peptide complex for nutritional support of cancer patients, and a preparation method and application thereof, which synergistically plays an anti-tumor adjuvant role, provides nutritional support for cancer patients after chemotherapy, reduces the side effects of chemotherapy and improves the quality of life.

[0005] In order to achieve the above-mentioned application purposes, the present application provides the following technical solutions:

[0006] A ginsenoside-protein peptide complex for nutritional support of cancer patients, comprising the following raw materials by weight: ginsenoside Rg3 5-7 parts, ginsenoside Rh2 2-4 parts, Compound K 0.5-1.5 parts, whey protein peptide 80-120 parts, marine fish scale peptide 25-40 parts, beta-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 part.

[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 with liposomes, and the encapsulation rate is ≥ 90%.

[0010] The application further provides a preparation method of the compound, comprising the following steps: dissolving ginsenoside Rg3, ginsenoside Rh2 and Compound K in an ethanol solution, performing microencapsulation embedding to obtain a microencapsulated ginsenoside mixture; dissolving whey protein peptides and marine fish scale peptides in water, adding β-glucan and HMB, and homogenizing to obtain a protein peptide base solution; and adding the microencapsulated ginsenoside mixture, nano-curcumin, sodium butyrate, N-acetylcysteine, vitamin C and selenium yeast into the protein peptide base solution, and mixing and drying to obtain the compound.

[0011] Preferably, the volume fraction of the ethanol solution is 50%-70%; and the wall material of the microencapsulation embedding is hydroxypropyl-β-cyclodextrin, and 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 is 1-2 times.

[0013] Preferably, the drying is performed by freeze-drying, and the water content of the compound is < 5%.

[0014] The application further provides an application of the ginsenoside-protein peptide compound in preparation of a nutritional support product for cancer patients after chemotherapy.

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

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

[0017] (1) Multi-dimensional synergistic nutritional support and anti-tumor assistance. The compound of the application forms an anti-tumor-nutritional supplement-immune regulation synergistic network through scientific proportioning of ginsenosides, small molecule protein peptides and functional ingredients, which can not only inhibit tumor angiogenesis and induce apoptosis of cancer cells, but also provide efficient amino acid supply for chemotherapy patients and reverse muscle loss caused by cachexia.

[0018] (2) Significantly reducing the side effects of chemotherapy. Through the multi-target effects of sodium butyrate in repairing intestinal mucosal barrier, nano-curcumin in anti-inflammation and anti-oxidation, and N-acetylcysteine in neutralizing hepatorenal toxicity, the incidence of diarrhea, oral mucositis and bone marrow suppression caused by chemotherapy is significantly reduced, and the treatment tolerance of patients is improved.

[0019] (3) Improving clinical outcomes. Through clinical verification, the compound can increase the patient's weight maintenance rate by 12.5%, increase the serum prealbumin level by 34%, reduce the incidence of grade III / IV chemotherapy side effects by 47%-60%, and increase the appetite and overall quality of life score by 36% or more, providing an innovative solution for post-chemotherapy nutritional support.

[0020] (4) Improving bioavailability and stability. The present application uses microencapsulation to embed ginsenosides, liposome-embedded nanocurcumin, and combines freeze-drying technology 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 application provides a ginsenoside-protein peptide compound for nutritional support of cancer patients, which comprises the following raw materials by weight: ginsenoside Rg3 5-7 parts, ginsenoside Rh2 2-4 parts, Compound K 0.5-1.5 parts, whey protein peptide 80-120 parts, marine fish scale peptide 25-40 parts, beta-glucan 8-12 parts, nanocurcumin 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 part.

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

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

[0024] Ginsenoside Rh2 can induce cancer cell apoptosis, inhibit metastasis, and alleviate chemotherapy-induced bone marrow suppression. Preferably, ginsenoside Rh2 is 2-4 parts, more preferably 3 parts.

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

[0026] Ginsenoside Rg3, Rh2 and Compound K are used in combination to form an anti-tumor-immune synergistic network, which can improve the response rate of chemotherapy and reduce the risk of tumor progression.

[0027] In the present application, protein peptides are composed of whey protein peptides and marine fish scale peptides; wherein:

[0028] Whey protein peptides can quickly provide essential amino acids, inhibit muscle decomposition, and promote synthesis. Preferably, 90-110 parts of whey protein peptides, further preferably 100 parts, and more preferably whey protein peptides with a molecular weight of 300-600 Da.

[0029] Marine fish scale peptides can resist inflammation and repair tissue damage; hydroxyproline promotes collagen regeneration. Preferably, 28-35 parts of marine fish scale peptides, further preferably 30 parts, and more preferably marine fish scale peptides with a molecular weight of 500-800 Da.

[0030] In the present application, 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 to enhance innate immune response. Preferably, 9-11 parts of β-glucan, and more preferably 10 parts.

[0032] Nano-curcumin can effectively resist inflammation and oxidation, reduce chemotherapy mucositis; and synergistically inhibit tumor growth with Rg3. Preferably, 18-22 parts of nano-curcumin, and more preferably 20 parts. Preferably, nano-curcumin is embedded in liposomes with an encapsulation efficiency of ≥90%, and further preferably a particle size of 100±20 nm. As an implementable mode, curcumin liposomes are prepared by a thin film hydration-ultrasonic extrusion method. The specific steps are as follows: soybean 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 organic solvent residues; then, preheated to 60°C phosphate buffer solution (PBS, pH 7.4) is added, and hydrated for 1 hour to obtain a crude liposome suspension; the crude suspension is sequentially filtered through 0.8 μm, 0.45 μm and 0.22 μm microporous membranes, and finally extruded through 200 nm and 100 nm polycarbonate membranes at 60°C for 10 times each time using a high-pressure extruder to obtain a nano-liposome suspension.

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

[0034] Sodium butyrate can repair intestinal mucosal barrier, reduce systemic inflammation caused by bacterial translocation; and inhibit histone deacetylation (HDAC) to resist tumors. Preferably, 38-45 parts of sodium butyrate, and more preferably 40 parts.

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

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

[0037] Selenium yeast can enhance immune cell activity and reduce the risk of infection. It can also synergistically enhance the activity of antioxidant enzymes with vitamin C. Preferably, 0.8-1 parts of selenium yeast, more preferably 1 part.

[0038] Marine fish scale peptide, HMB and curcumin play a synergistic role in anti-inflammatory and muscle protection, reducing muscle loss in cachexia patients and stabilizing body weight. Whey protein peptide, sodium butyrate and N-acetylcysteine reduce the incidence of chemotherapy-related diarrhea and reduce liver damage. Nano-curcumin, vitamin C and selenium yeast reduce oxidative stress after chemotherapy. The ginsenoside-protein peptide complex of the present application can play an anti-tumor auxiliary role, provide nutritional support for cancer patients after chemotherapy, reduce the side effects of chemotherapy, and improve the quality of life.

[0039] The present application also provides a preparation method of the above-mentioned complex, comprising the following steps:

[0040] (1) Dissolve ginsenosides Rg3, Rh2 and Compound K in an ethanol solution, and perform microencapsulation embedding to obtain a microencapsulated ginsenoside mixture.

[0041] In the present application, the volume fraction of the ethanol solution is preferably 50%-70%, and further preferably 60%. The wall material for microencapsulation embedding is preferably hydroxypropyl-β-cyclodextrin, and the wall-to-core mass ratio is 2:1, with an embedding rate of ≥95%. Further preferably, it is sieved through a 100-mesh sieve. More preferably, the microencapsulation embedding step is as follows:

[0042] A. Mix Rg3, Rh2 and Compound K according to the mass ratio; add 60% ethanol solution, control the temperature at 45±2℃; stir at a speed of 800 rpm until complete dissolution, and obtain a clear solution;

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

[0044] C. Slowly add the saponin ethanol solution to the hydroxypropyl-β-cyclodextrin water solution according to a wall-to-core mass ratio of 2:1, maintain a water bath at 50±1℃, and mechanically stir at 500 rpm for 4 hours; adjust the pH to 8.0-8.5 with a sodium bicarbonate buffer system;

[0045] D. Filter the reaction solution through a 0.45μm filter membrane to remove unencapsulated substances; remove free saponins by dialysis (molecular weight cutoff 1kDa); and freeze-dry to obtain a microencapsulated ginsenoside mixture.

[0046] (2) Dissolve the whey protein peptide and marine fish scale peptide in water, add β-glucan and HMB, and homogenize to obtain a protein peptide base solution.

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

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

[0049] In the present application, preferably, the mixing is performed at 30-40°C with stirring at 200-300 rpm, and further preferably, the mixing is performed at 35°C with stirring at 250 rpm to avoid foam generation.

[0050] (4) Dry to obtain a complex.

[0051] In the present application, preferably, the drying is performed by freeze-drying until the water content of the complex is <5%; further preferably, the freeze-drying parameters are: pre-freezing at -45°C±2°C for 4-5 hours, vacuum degree 0.1-0.2 mbar, temperature gradient 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 application, preferably, the complex is further subjected to (5) sterilization and (6) packaging, and further preferably:

[0053] (5) 60 Co-γ-ray irradiation sterilization, and more preferably, the irradiation dose is 8-12 kGy. The irradiation sterilization can effectively kill bacteria and avoid affecting the properties of the complex.

[0054] (6) Aluminum foil bag packaging, nitrogen filling and airtight sealing, and more preferably, the residual oxygen after nitrogen filling is ≤1%, which prolongs the shelf life of the complex and facilitates circulation and carrying.

[0055] In the absence of special instructions, the above raw materials of the present application can be obtained through market channels, and the preparation methods can be prepared by using common equipment in the art.

[0056] The present application also provides the use of the above 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 the side effects of chemotherapy and enhancing immune function, and further preferably, the addition amount of the complex in the product is 0.5wt%-99.5wt%, and more preferably 20wt%-80wt%.

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

[0058] Example 1

[0059] A ginsenoside-protein peptide complex for nutritional support of cancer patients, raw materials as follows:

[0060] Ginsenoside Rg3 5 parts, ginsenoside Rh2 2 parts, Compound K 0.5 parts, whey protein peptide 80 parts (molecular weight 300-600 Da), marine fish scale peptide 25 parts (molecular weight 500-800 Da), 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] Dissolve Rg3, Rh2 and Compound K in an ethanol solution with a volume fraction of 50% (45°C water bath), and stir at a speed of 800 rpm until completely dissolved; dissolve hydroxypropyl-β-cyclodextrin in pure water at 50°C according to a core-to-wall mass ratio of 2:1 (concentration 15% w / v), slowly drop the saponin solution into the cyclodextrin solution, stir at 50°C for 4 hours, and adjust the pH to 8.0; filter the reaction solution through a 0.45 μm filter membrane, remove free saponins by dialysis (molecular weight cutoff 1 kDa), and freeze-dry (-45°C pre-freezing for 4 hours, main drying at -25°C to -10°C, vacuum degree 0.1 mbar, analytical drying at 25°C, 0.01 mbar) to obtain a microencapsulated mixture.

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

[0065] Dissolve whey protein peptide and marine fish scale peptide in purified water at 40°C, and add β-glucan and HMB, and homogenize at 15 MPa for one time.

[0066] (3) Mixing and drying:

[0067] Add microencapsulated ginsenoside mixture, nano-curcumin, sodium butyrate, etc. to the protein peptide base solution, mix by stirring at 30°C and 200 rpm, and freeze-dry to a water content of <5%.

[0068] Example 2

[0069] A ginsenoside-protein peptide complex for nutritional support of cancer patients, raw materials as follows:

[0070] Ginsenoside Rg37 parts, ginsenoside Rh24 parts, Compound K 1.5 parts, whey protein peptide 120 parts (molecular weight 300-600 Da), marine fish scale peptide 40 parts (molecular weight 500-800 Da), 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, which is the same as that in Example 1:

[0072] (1) Preparation of microencapsulated ginsenosides:

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

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

[0075] Whey protein peptide and marine fish scale peptide are dissolved in 50°C purified water, and β-glucan, HMB are added and homogenized at 25 MPa for 2 times.

[0076] (3) Mixing and drying:

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

[0078] Example 3

[0079] A ginsenoside-protein peptide complex for nutritional support of cancer patients, the raw materials are as follows:

[0080] Ginsenoside Rg36.5 parts, ginsenoside Rh23.5 parts, Compound K 1.2 parts, whey protein peptide 110 parts (molecular weight 300-600 Da), marine fish scale peptide 35 parts (molecular weight 500-800 Da), 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, which is the same as that in Example 1:

[0082] (1) Preparation of microencapsulated ginsenosides:

[0083] Rg3, Rh2, Compound K are dissolved in 60% ethanol solution, stirred to dissolve at 45℃, and microencapsulated for embedding.

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

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

[0086] (3) Mixing and drying:

[0087] After each component is added to the base solution, it is mixed at 35℃ and 250rpm, and freeze-dried to a water content of <5%.

[0088] Example 4

[0089] A ginsenoside-protein peptide complex for nutritional support of cancer patients, the raw materials are as follows:

[0090] Ginsenoside Rg3 5.5 parts, ginsenoside Rh2 2.5 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 the parameters are the same as in Example 1:

[0092] (1) Preparation of microencapsulated ginsenosides:

[0093] Rg3, Rh2, Compound K are dissolved in 55% ethanol solution, stirred to dissolve at 45℃, and microencapsulated for embedding.

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

[0095] Whey protein peptide and marine fish scale peptide are dissolved in pure water at 42℃, and β-glucan and HMB are added and homogenized at 18MPa for two times.

[0096] (3) Mixing and drying:

[0097] After each component is added to the base solution, it is mixed at 32℃ and 220rpm, and freeze-dried to a water content of <5%.

[0098] Example 5

[0099] A ginsenoside-protein peptide complex for nutritional support of cancer patients, the raw materials are as follows:

[0100] Ginsenoside Rg36 parts, ginsenoside Rh23 parts, Compound K 1 part, whey protein peptide 100 parts (molecular weight 300-600 Da), marine fish scale peptide 30 parts (molecular weight 500-800 Da), 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, which is the same as that in Example 1:

[0102] (1) Preparation of microencapsulated ginsenosides:

[0103] Rg3, Rh2, and Compound K are dissolved in a 60% ethanol solution, stirred and dissolved at 45°C, and subjected to microencapsulation embedding treatment.

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

[0105] Whey protein peptide and marine fish scale peptide are dissolved in purified water at 45°C, and β-glucan and HMB are added and homogenized at 20 MPa for 2 times.

[0106] (3) Mixing and drying:

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

[0108] Comparative Example 1

[0109] The same as Example 5, except that the raw materials do not contain a 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 ginsenoside-protein peptide complex samples of Examples 1-5 were subjected to physical property detection, and the specific method was as follows:

[0120] (1) Test of reconstitution and dispersibility

[0121] 10 g of the freeze-dried powder of each of Examples 1-5 was dissolved in 200 mL of warm water (40°C ± 2°C), and 200 rpm magnetic stirring was performed. The complete dissolution time (no particles were observed visually) was recorded. After standing for 2 h, the sedimentation rate was measured (centrifugation at 3000 x g for 10 min).

[0122] Test results: As shown in Table 1, the reconstitution time of the complex of Examples 1-5 was ≤60 s, and the sedimentation rate was ≤3%, both of which were qualified products (Chinese Pharmacopoeia 2020).

[0123] Table 1 Reconstitution and dispersibility of the complex of Examples 1-5

[0124]

[0125] (2) Measurement of flowability parameters

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

[0127] Test results: As shown in Table 2, the angle of repose of the complex of Examples 1-5 was <40°, and the compressibility was <25%, both of which were acceptable (USP <1174>).

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

[0129]

[0130] (3) Sensory evaluation

[0131] The taste of Examples 1-5 was evaluated by cancer patients after chemotherapy. The complex 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. Test design

[0135] (1) Research subjects

[0136] Inclusion criteria: patients with solid tumors diagnosed by pathology (lung cancer, colorectal cancer, breast cancer), aged 25-50 years, receiving platinum or taxane-containing chemotherapy regimen (≥2 cycles), ECOG score ≤2 points, expected survival >3 months, body mass index (BMI) 18.5-24.9 kg / m 2 .

[0137] Exclusion criteria: severe liver and kidney dysfunction (ALT / AST >3×ULN, Cr >1.5×ULN), gastrointestinal obstruction, combined 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 Examples 1-5 group, and Example 5 group) according to the random number table method, with 20 patients in each group, and the gender, age, and tumor type were matched (P P >0.05).

[0139] (2) Intervention measures

[0140] Control group: conventional nutritional support (25-30 kcal / kg per day, 1.0-1.2 g / kg of protein) was given without adding the compound of the application. Example 5 group and Comparative Examples 1-5 group were orally administered twice a day (once in the morning and once in the evening, 5 g each time, dissolved in 200 mL of warm water). The intervention was continued for 8 weeks from the beginning of the first cycle of chemotherapy.

[0141] 2. Index detection method

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

[0143] Body weight maintenance rate: body weight was measured at a fixed time each week (fasting in the morning), and the proportion of patients with a body weight decrease of ≤5% in 8 weeks was calculated.

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

[0145] (2) Chemotherapy side effect control indicators

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

[0147] Oral mucositis: WHO grading standard was used, and III grade was defined as ulcer with pain, unable to eat, and IV grade was ulcer with bleeding or infection.

[0148] Neutropenia: Blood routine examination was detected every week after chemotherapy, and neutrophil count <1.5 x 10 9 / L was defined as abnormal.

[0149] (3) Quality of life score

[0150] Appetite score (FAACT appetite subscale): including 6 items (such as "loss of appetite" "decrease in food intake"), using 5-point scale (0 = completely no, 4 = very severe), the total score is converted into standard score (full score 50 points), the higher the score, the better the appetite.

[0151] Fatigue score (FACIT-F): 27-item self-report questionnaire, 5-point scale, total score is converted into standard score (full score 108 points), the lower the score, the more severe the fatigue.

[0152] Overall quality of life: EORTC QLQ-C30 scale was used, including physical, role, emotional, social function and other dimensions, the total score is converted into standard score (full score 100 points), the higher the score, the better the quality of life.

[0153] 3. Statistical analysis

[0154] SPSS 26.0 software was used, measurement data was represented by x ± s, one-way ANOVA was used for comparison between groups, and LSD-t test was used for pairwise comparison; count data was represented by rate (%), and chi-square test was used. P P <0.05 indicates that the difference is statistically significant.

[0155] 4. Test results

[0156] (1) As shown in Table 3, the weight maintenance rate of Example 5 group (92.6%) was significantly higher than that of the control group (82.3%), the average weight gain was 0.4 kg, and the serum prealbumin level reached 22.5 mg / dL, confirming that the complex of the application improves the efficiency of amino acid absorption by combining small molecular peptides of whey protein peptides and marine fish scale peptides, and inhibits muscle decomposition. The weight of the comparative example 2 group decreased by 4.1 kg, and the prealbumin level was the lowest (14.2 mg / dL), indicating that protein peptides are the core component for improving cachexia; the weight maintenance rate of the comparative example 5 group was only 75.4%, proving the auxiliary role of β-glucan, HMB and other components on weight stability.

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

[0158]

[0159] (2) As shown in Table 4, the Example 5 group shows a significant advantage in the control of chemotherapy side effects. The incidence of III / IV grade diarrhea is only 15%, which is significantly lower than 40% of the control group and all the comparative groups, which is due to the promotion of intestinal mucosal epithelial cell proliferation by sodium butyrate, combined with the increase of glutathione level by N-acetylcysteine, to reduce the cisplatin-induced intestinal mucosal damage. The incidence of oral mucositis is 30%, which is 60% lower than 75% of the control group, indicating that the components synergistically promote collagen synthesis and accelerate ulcer healing. The incidence of neutropenia is 45%, which is significantly lower than 85% of the control group, reflecting the role of ginsenoside Rh2 in promoting hematopoietic stem cell proliferation, and Compound K in activating intestinal flora metabolites, short-chain fatty acids, and indirectly enhancing the support capacity of bone marrow microenvironment.

[0160] Table 4 Effect of different compound groups on the control of chemotherapy side effects of patients

[0161]

[0162] (3) As shown in Table 5, the appetite score of the Example 5 group (35.6 points) is increased by 41% compared with the control group (25.3 points), the fatigue score (38.7 points) is reduced by 30%, and the overall quality of life (68.5 points) is increased by 36%. This is due to the multi-target synergy of HMB in the compound of the present application 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 is only 56.7 points, which shows the importance of the antioxidant system of nano-curcumin, vitamin C and selenium yeast in reducing oxidative stress of chemotherapy; the appetite score of the comparative example 4 group is only 26.4 points, which proves the necessity of sodium butyrate and HMB for gastrointestinal function recovery.

[0163] Table 5 Quality of life score of patients in different compound groups

[0164]

[0165] As can be seen from the above, the compound of the present application significantly improves the clinical outcome of cancer patients after chemotherapy through the three-dimensional synergistic mechanism of ginsenosides, protein peptides and functional ingredients. In terms of nutritional metabolism, small molecule protein peptides and HMB synergistically increase body weight maintenance rate and serum prealbumin level, effectively reversing cachexia; in terms of toxic side effects, ginsenosides combined with nano-curcumin reduce the incidence of III / IV grade mucositis, sodium butyrate and N-acetylcysteine reduce the risk of diarrhea, and the incidence of neutropenia is reduced; in terms of quality of life, multi-component synergy increases appetite score, significantly relieves fatigue, and the overall quality of life score reaches 68.5 points, which is a breakthrough improvement compared with traditional nutritional support programs.

[0166] The advantages of the compound of the present application compared with single component or partial component combination are: the bioavailability of ginsenoside is improved by microencapsulation embedding, and the double activation of anti-tumor-anti-inflammatory pathway is formed with nano-curcumin; the molecular weight optimization of whey protein peptide and marine fish scale peptide ensures rapid absorption, and forms a closed loop network of nutrient absorption-mucosal repair-immune regulation with components such as β-glucan and sodium butyrate.

[0167] The above only describes the preferred embodiments of the present application, and it should be pointed out that for ordinary skilled in the art, without departing from the principles of the present application, a number of improvements and refinements can be made, and these improvements and refinements should be considered as the protection scope of the present application.

Claims

1. A ginsenoside-protein peptide complex for nutritional support in cancer patients, characterized in that, It is made from the following raw materials in parts by weight: 5-7 parts ginsenoside Rg3, 2-4 parts ginsenoside Rh2, 0.5-1.5 parts Compound K, 80-120 parts whey protein peptide, 25-40 parts marine fish scale peptide, 8-12 parts β-glucan, 15-25 parts nano-curcumin, 20-30 parts HMB, 35-50 parts sodium butyrate, 40-60 parts N-acetylcysteine, 40-60 parts vitamin C, and 0.6-1 parts selenium yeast; The molecular weight of whey protein peptides is 300-600 Da; the molecular weight of the marine fish scale peptides is 500-800 Da. The nano-curcumin was prepared by encapsulating curcumin in liposomes, with an encapsulation rate of ≥90%. The preparation method of the ginsenoside-protein peptide complex includes the following steps: Ginsenosides Rg3, Rh2, and Compound K were dissolved in an ethanol solution and microencapsulated to obtain a microencapsulated ginsenoside mixture. Whey protein peptides and marine fish scale peptides were dissolved in water, and β-glucan and HMB were added. After homogenization, a protein peptide base solution was obtained. The microencapsulated ginsenoside mixture, nano-curcumin, sodium butyrate, N-acetylcysteine, vitamin C, and selenium yeast were added to the protein peptide base solution and mixed, then dried to obtain the complex.

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

1.

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

4. The complex according to claim 1, characterized in that, The water is purified water; the homogenization pressure is 15-25 MPa, and the homogenization is performed 1-2 times.

5. The complex according to claim 1, characterized in that, The drying process employs freeze drying until the water content of the composite is <5%.

6. The use of the ginsenoside-protein peptide complex according to any one of claims 1-5 in the preparation of nutritional support products for cancer patients after chemotherapy.

7. The application according to claim 6, characterized in that, The nutritional support includes improving cachexia, reducing chemotherapy side effects, and enhancing immune function.

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