Ganoderma lucidum polysaccharide uses and ganoderma lucidum polysaccharide flavonoid compositions and methods of making and uses thereof

Abstract

This invention relates to the uses of Ganoderma lucidum polysaccharides and a Ganoderma lucidum polysaccharide-lactoxin composition, its preparation method, and its uses. Specifically, it relates to the uses of Ganoderma lucidum polysaccharides in improving the bioavailability of lactoxin; the uses of the Ganoderma lucidum polysaccharide-lactoxin composition in the preparation of drugs for treating and / or preventing osteoarthritis and osteoporosis; the uses of the Ganoderma lucidum polysaccharide-lactoxin composition in the preparation of drugs for treating and / or preventing neurodegenerative diseases; and the uses of the Ganoderma lucidum polysaccharide-lactoxin composition in the preparation of anti-inflammatory drugs. It also includes a method for preparing the Ganoderma lucidum polysaccharide-lactoxin composition.

Description

Technical Field

[0001] This invention relates to the uses of Ganoderma lucidum polysaccharides and Ganoderma lucidum polysaccharide-lactoxin compositions, their preparation methods, and uses. Specifically, it relates to novel uses of Ganoderma lucidum polysaccharides in improving the bioavailability of lactoxin; uses of Ganoderma lucidum polysaccharides and lactoxin compositions in the preparation of anti-aging drugs, health products, or foods; uses of Ganoderma lucidum polysaccharides and lactoxin compositions in the preparation of products that improve skin condition, soothe skin, repair skin, tighten skin, whiten skin, or reduce wrinkles; uses of Ganoderma lucidum polysaccharides and lactoxin compositions in the preparation of drugs, health products, or foods for treating and / or preventing osteoarthritis and osteoporosis; uses of Ganoderma lucidum polysaccharides and lactoxin compositions in the preparation of drugs, health products, or foods for treating and / or preventing neurodegenerative diseases; and uses of Ganoderma lucidum polysaccharides and lactoxin compositions in the preparation of anti-inflammatory drugs, health products, or foods. The invention also includes a method for preparing Ganoderma lucidum polysaccharide-lactoxin compositions. Background Technology

[0002] Fisetin is a naturally occurring flavonoid compound, belonging to plant secondary metabolites, and is widely distributed in various fruits, vegetables, and trees. Chemical name: 3,3',4',7-tetrahydroxyflavone. Molecular formula: C 15 H 10 O6. Sources: Strawberries, apples, persimmons, grapes, onions, cucumbers, etc., especially found in Anacardiaceae plants (such as Cotinus coggygria). Solubility: Lipid-soluble, slightly soluble in water, readily soluble in organic solvents (such as ethanol, DMSO).

[0003] Rhus flavin has been extensively studied for its antioxidant and signaling pathway regulation effects, and has the following functions: (1) Antioxidant and anti-inflammatory: It scavenge free radicals and inhibit oxidative stress. It regulates inflammatory pathways such as NF-κB and reduces chronic inflammation. (2) Neuroprotection: It activates antioxidant pathways (such as Nrf2) and reduces nerve cell damage. Studies have shown that it can delay Alzheimer's disease and Parkinson's disease. (3) Anti-aging and longevity: As a senolytic agent (to clear senescent cells), it prolongs the lifespan of model organisms. It activates SIRT1 (a longevity-related protein). (4) Anti-cancer potential: It can inhibit pathways such as PI3K / AKT and mTOR and induce apoptosis in cancer cells. It may have inhibitory effects on breast cancer and prostate cancer. (5) Metabolic regulation: It can improve insulin sensitivity and has the potential to assist in the management of diabetes.

[0004] Currently, the bioavailability of rutin is low, with an oral bioavailability of only 5-10%. This is mainly limited by the following factors: (1) Poor solubility: It is a lipid-soluble molecule with low gastrointestinal absorption. (2) First-pass metabolism: It is rapidly metabolized in the liver and intestines by UGT (uridine diphosphate glucuronide transferase) and SULT (sulfotransferase) into glucuronic acid or sulfate derivatives. (3) Intestinal flora metabolism: It is partially degraded by intestinal microorganisms.

[0005] In the prior art, the existing strategies to improve the bioavailability of rutin are as follows: (1) Nanodelivery system: liposomes, polymer nanoparticles (such as PLGA), micelle encapsulation can improve solubility, delay metabolism, and target release; (2) Structural modification: synthesizing methylated or acetylated derivatives (such as 7,8-dimethylrutin) can reduce UGT metabolism and prolong half-life; (3) Combination administration: combined with piperine (CYP3A4 inhibitor) or quercetin (competitive metabolic enzyme) can reduce first-pass metabolism and increase blood drug concentration; (4) Novel dosage form: self-microemulsion (SMEDDS) and solid dispersion (such as combined with PVP) can enhance intestinal absorption.

[0006] Experimental studies have shown that encapsulation of lacquer citrate in nanoliposomes increases its bioavailability to 25% in a rat model. Encapsulation of lacquer citrate with γ-cyclodextrin increases water solubility by 10-fold and Cmax (maximum plasma concentration) by 3-fold. Based on current research, the bioavailability of lacquer citrate remains low, necessitating further investigation. Summary of the Invention

[0007] The purpose of this invention is to provide a composition of Ganoderma lucidum polysaccharide and rosin.

[0008] The purpose of this invention is to provide the use of Ganoderma lucidum polysaccharides in improving the bioavailability of rutin.

[0009] The purpose of this invention is to provide the use of Ganoderma lucidum polysaccharides in improving the bioavailability of rutin.

[0010] The purpose of this invention is to provide the use of a combination of Ganoderma lucidum polysaccharides and rutin in the preparation of anti-aging drugs. Experiments have shown that the combination of Ganoderma lucidum polysaccharides and rutin exerts anti-aging effects in bone, cardiovascular, skin, and muscle areas by regulating stem cell function, mimicking calorie restriction to prolong life, restoring cellular homeostasis, and activating genes such as Sirt and IL-23R.

[0011] The purpose of this invention is to provide the use of a combination of Ganoderma lucidum polysaccharides and rutin in the preparation of drugs for the treatment and / or prevention of osteoarthritis and osteoporosis. Experiments have shown that the combination of Ganoderma lucidum polysaccharides and rutin can inhibit osteoclast differentiation, promote osteoblast formation, increase bone mass and bone density, and prevent osteoporosis, osteoarthritis, intervertebral disc degeneration, and other skeletal diseases; it also accelerates the autophagic clearance of senescent muscle cells, enhances energy supply, and improves the exercise capacity, cardiopulmonary function, endurance, and muscle strength of aging individuals.

[0012] The purpose of this invention is to provide the use of a combination of Ganoderma lucidum polysaccharides and flavin in the preparation of drugs for the treatment and / or prevention of neurodegenerative diseases. Experiments have shown that the combination of Ganoderma lucidum polysaccharides and flavin can reduce oxidative damage and neuroinflammation of nerve cells; restore nerve function after spinal cord injury; improve cognition and enhance memory; and reduce anxiety, relieve stress, and regulate mood.

[0013] The purpose of this invention is to provide the use of a combination of Ganoderma lucidum polysaccharides and rutin in the preparation of anti-inflammatory drugs. Experiments have shown that the combination of Ganoderma lucidum polysaccharides and rutin can improve skin inflammation, alleviate UVA-induced skin damage, treat psoriasis, chronic urticaria, and other skin diseases caused by impaired immune function; reduce lung inflammation and oxidative stress, remodel airway smooth muscle, and treat lung damage and asthma caused by inflammation.

[0014] In the aforementioned Ganoderma lucidum polysaccharide and lacquer flavonoid composition, the weight ratio of Ganoderma lucidum polysaccharide to lacquer flavonoid is 18-40:10-30.

[0015] The composition is a Ganoderma lucidum polysaccharide inclusion complex of rutin.

[0016] The preparation method of the Ganoderma lucidum polysaccharide and laccasein composition includes the following steps:

[0017] Take Ganoderma lucidum polysaccharide, rutin, and deionized water equivalent to 3-10 times the weight of Ganoderma lucidum polysaccharide, grind and mix them, then filter and mix them through a 200-800um microfluidic chip, then freeze-dry them, and then pulverize the freeze-dried product and pass it through a 200-800 mesh sieve to obtain the final product.

[0018] The grinding and mixing are carried out in a high-energy ball mill, with the temperature controlled at 25-40℃.

[0019] The freeze-drying time is 24-48 hours.

[0020] Experimental studies have shown that Ganoderma lucidum polysaccharides can significantly improve the bioavailability of flavin, with a relative bioavailability 10.16 times that of the flavin group and 3.63 times that of the phospholipid group, and an absolute bioavailability of over 29%.

[0021] Pharmacological experiments have demonstrated that the complex of Ganoderma lucidum polysaccharides and rutin exhibits a significant synergistic effect, noticeably enhancing anti-aging and anti-inflammatory efficacy, as well as significantly improving the treatment of osteoarthritis, osteoporosis, and neurodegenerative diseases. Furthermore, it also improves skin condition, soothes, repairs, firms, whitens, and reduces wrinkles. Attached Figure Description

[0022] Figure 1 It is the linear regression equation of the standard curve of laccoside in Example 5;

[0023] Figure 2 This is the oral administration-drug duration curve of laccasein in Example 5;

[0024] Figure 3 This is the oral administration-drug cycle curve of rosin + arabinose in Example 5;

[0025] Figure 4 This is the oral administration-drug time curve of the rutin + Ganoderma lucidum polysaccharide sample in Example 5;

[0026] Figure 5 This is the oral administration-drug duration curve of the rutin + chitosan sample in Example 5;

[0027] Figure 6 This is the oral administration-drug cycle curve of the laccase + phospholipid sample from Example 5;

[0028] Figure 7 Overall dosing-time curve of lacquer xanthocyanin in Example 5;

[0029] Figure 8 This is a comparison chart of Cmax for each group of samples;

[0030] Figure 9 This is a comparison chart of the half-lives of each group of samples;

[0031] Figure 10 This is a comparison chart of Tmax for each group of samples;

[0032] Figure 11 This is a comparison chart of the MRT values ​​of each group of samples;

[0033] Figure 12 This is a comparison chart of the absolute bioavailability of each group of samples.

[0034] Figure 13 This is a comparison chart of the relative bioavailability of each group of samples. Detailed Implementation

[0035] The present invention is further illustrated below by way of examples. It should be understood that the examples are for illustrative purposes only and not for limiting the invention. Simple modifications made to the invention based on its essence are within the scope of protection claimed by the present invention. Unless otherwise stated, percentages in the present invention are weight percentages (volume percentages for ethanol).

[0036] Example 1

[0037] Rhus flavin-Ganoderma lucidum polysaccharide inclusion complex:

[0038] 18kg of Ganoderma lucidum polysaccharides

[0039] 11kg of lacquer yellow pigment

[0040] The purity of laccoside is 98%.

[0041] The preparation method of the inclusion complex includes the following steps:

[0042] Weigh out Ganoderma lucidum polysaccharide and rutin by weight, add 54 kg of deionized water, grind and mix them in a high-energy ball mill, control the grinding and mixing temperature at 25℃, then filter and mix them through a 200 μm microfluidic chip, and then freeze-dry for 24 hours. The freeze-dried product is then pulverized and passed through a 200-mesh sieve to obtain the final product.

[0043] Example 2

[0044] Rhus flavin-Ganoderma lucidum polysaccharide inclusion complex:

[0045] 40kg of Ganoderma lucidum polysaccharides

[0046] 30kg of lacquer yellow pigment

[0047] The purity of laccoside is 98%.

[0048] The preparation method of the inclusion complex includes the following steps:

[0049] Weigh out Ganoderma lucidum polysaccharides and rutin by weight, add 400 kg of deionized water, grind and mix them in a high-energy ball mill, control the grinding and mixing temperature at 40℃, then filter and mix them through an 800 μm microfluidic chip, and then freeze-dry for 48 hours. The freeze-dried product is then pulverized and passed through an 800-mesh sieve to obtain the final product.

[0050] Example 3

[0051] Rhus flavin-Ganoderma lucidum polysaccharide inclusion complex:

[0052] 25kg of Ganoderma lucidum polysaccharides

[0053] 25kg of lacquer yellow pigment

[0054] The purity of laccoside is 98%.

[0055] The preparation method of the inclusion complex includes the following steps:

[0056] Weigh out Ganoderma lucidum polysaccharides and rutin by weight, add 150 kg of deionized water, grind and mix them in a high-energy ball mill, control the grinding and mixing temperature at 30℃, then filter and mix them through a 400 μm microfluidic chip, and then freeze-dry for 30 hours. The freeze-dried product is then pulverized and passed through a 400 mesh sieve to obtain the final product.

[0057] Example 4

[0058] Rhus flavin-Ganoderma lucidum polysaccharide inclusion complex:

[0059] 32kg of Ganoderma lucidum polysaccharides

[0060] 20kg of lacquer yellow pigment

[0061] The purity of laccoside is 98%.

[0062] The preparation method of the inclusion complex includes the following steps:

[0063] Weigh out Ganoderma lucidum polysaccharide and rutin by weight, add 160 kg of deionized water, grind and mix them in a high-energy ball mill, control the grinding and mixing temperature at 32℃, then filter and mix them through a 600 μm microfluidic chip, and then freeze-dry for 36 hours. The freeze-dried product is then pulverized and passed through a 600 mesh sieve to obtain the final product.

[0064] Example 5: Bioavailability Experiment of Rhubarb

[0065] I. Experimental Objective

[0066] In accordance with the technical guidelines for drug pharmacokinetic studies, the bioavailability of different rutin-encapsulated samples in rats was determined.

[0067] 1. Preparation method of experimental group: The lacquinone-Ganoderma lucidum polysaccharide inclusion complex prepared in Example 4.

[0068] 2. Preparation method of control group:

[0069] (1) Oxalis xanthocyanin + Arabic gelatin inclusion complex:

[0070] Weigh out gum arabic and laccoside, add 160 kg of deionized water, grind and mix them in a high-energy ball mill at a temperature of 32°C, then filter and mix them through a 600 μm microfluidic chip, and then freeze-dry for 36 hours. Finally, pulverize the freeze-dried product and pass it through a 600-mesh sieve to obtain the final product.

[0071] (2)Fisetin + chitosan inclusion compound:

[0072] At room temperature, 0.2% w / v chitosan (CS) was dissolved in 50 mL of 1% v / v aqueous acetic acid solution and stirred overnight at 600 rpm. The pH of the CS solution was adjusted to 5 using a 2M NaOH solution. The CS solution was then filtered through a 0.45 μm filter to separate any insoluble CS. Sodium tripolyphosphate was dissolved in distilled water under magnetic stirring to obtain a 1 mg / mL tripolyphosphate solution (TPP).

[0073] A 2 mg / mL Fisetin solution was prepared in a mixture of water and DMSO (4:1) and added dropwise to a CS solution of 5 times its volume while stirring at 400 rpm for 1 h. Next, a 2.5 times volume TPP solution was added dropwise to the Fisetin-containing CS solution at the same stirring speed, at a rate of 1 mL / min. To separate the nanoparticles, the resulting suspension was centrifuged at 12,000 rpm for 20 min (4 °C), washed twice with distilled water, centrifuged again, and the precipitate was resuspended in distilled water and lyophilized to obtain FIS-CS particles.

[0074] (3) Rhus flavin + lecithin inclusion complex:

[0075] Use soybean phosphatidylcholine ( S100 was mixed with Fisetin at a 1:1 ratio, and 30% (v / v) anhydrous ethanol was added. The reaction mixture was then gently and magnetically stirred at 400 rpm for 1 h at 40-45 °C until a complex was formed. Subsequently, 10 mL of deionized water (equivalent to 30 mg Fisetin) was added to the FIS-SPC complex to form a phospholipid complex. The self-assembled vesicles were then sonicated in a water bath for 5 min (50 W / cm²). 2 The process continued until a clear dispersion was obtained. Finally, residual organic solvent was removed using a rotary evaporator under vacuum at 40°C. To further remove solvent, the dispersion was dried in an oven at 37°C for 2 hours. To achieve a suitable size reduction effect, the prepared phospholipid complex dispersion was placed in an ice bath and subjected to probe sonication again at 60% amplitude for 5 minutes (5 seconds on, 5 seconds off).

[0076] II. Sample Information

[0077] Yellow pigment Sealed bag, keep out of light pale yellow powder normal temperature Fibroin + Arabic gelatin The bottle should be sealed and kept away from light. Yellow powder normal temperature Ficus pluvialis + Ganoderma lucidum polysaccharide The bottle should be sealed and kept away from light. brown powder normal temperature Ficus flavin + chitosan The bottle should be sealed and kept away from light. Yellow powder normal temperature Fibroin + Lecithin The bottle should be sealed and kept away from light. Yellow powder normal temperature

[0078] III. Instruments and Reagents

[0079] 3.1 Reagents

[0080] Yellow pigment HPLC > 98% Shanghai McLean Biotechnology Co., Ltd. Formic acid HPLC grade CNW Technologies Acetonitrile HPLC grade CNW Technologies water Ultrapure water Watsons Veterinary saline 0.9% Sodium Chloride Injection Jiangsu Hengfengqiang Biotechnology Co., Ltd. Polyethylene glycol-400 (PEG400) AR level Sinopharm Chemical Reagent Co., Ltd.

[0081] 3.2 Instruments

[0082] Electronic analytical balance BS-3000A Shanghai Yousheng Weighing Instrument Co., Ltd. low-speed refrigerated centrifuge KDC-2046 Anhui Zhongke Zhongjia Scientific Instruments Co., Ltd. Ultra-high performance liquid chromatography ACQUITY UPLC Waters Corporation Triple quadrupole mass spectrometer TSQ Altis Thermo Fisher Scientific Microplate thermostatic oscillator BE-9010 Haimen Qilinbei Instrument Co., Ltd.

[0083] IV. Laboratory Animals and Their Housing Conditions

[0084] 4.1 Breed: SD rat;

[0085] 4.2 Level: SPF level;

[0086] 4.3 Number, sex, and weight range of animals to be purchased: 12 animals, male, 200-230g;

[0087] 4.4 Source: Guangzhou Ruige Biotechnology Co., Ltd.

[0088] 4.5 The quality certificate number for this batch of laboratory animals is: No. 44827200015375

[0089] 4.6 Identification Method: Write the number on the tail with a marker. Identification is achieved by marking the tail with a dual number: the tail number and the cage number.

[0090] 4.7 Animal Welfare: The content and procedures related to animal testing in this study will comply with the relevant laws and regulations on the use and management of laboratory animals and the relevant regulations of the Laboratory Animal Ethics Committee of this institution to ensure the welfare of laboratory animals.

[0091] 4.8 Safe suicide: carbon dioxide euthanasia; the body is temporarily stored in a morgue and will be disposed of in an environmentally friendly manner by our laboratory.

[0092] 4.9 Quarantine and observation: Purchased rats were quarantined for 5 days and observed once a day. Any unhealthy rats were immediately removed, and healthy rats were selected for the experiment.

[0093] 4.10 Animal husbandry and management: Animals are housed in the animal facility of Nanxin Instrument (Guangzhou) Manufacturing Co., Ltd. Animal housing conditions: 5 animals / cage, group housing;

[0094] Temperature and humidity for rearing: 20–26℃, 40–70%, with intermittent lighting at night and during the day (12h:12h). Conditions in the rearing room were kept stable at all times to ensure the reliability of the experimental results. Free access to food and water was provided by Nanxin Instruments (Guangzhou) Manufacturing Co., Ltd.

[0095] V. Dosage Design and Grouping

[0096] 5.1 After passing animal quarantine, the rats were randomly divided into 4 groups of 3 rats each, according to their body weight. The grouping and dosage are shown in Table 1 below.

[0097] Table 1 Dosage Design and Grouping

[0098]

[0099] VI. Experimental Methods

[0100] 6.1 Animal administration

[0101] 6.1.1 Preparation method of lacquer xanthoside gavage solution: Weigh 150mg of lacquer xanthoside in the dark, add an appropriate amount of 5%-PEG400 physiological saline to 15mL, and vortex for 5min to prepare lacquer xanthoside gavage solution. This gavage solution should be prepared fresh for use.

[0102] 6.1.2 Administration method: Group A rats were given lacquinone gavage solution by gavage; Group B rats were given lacquinone + arabinogelatin sample by gavage; Group C rats were given lacquinone + Ganoderma lucidum polysaccharide sample by gavage; Group D rats were given lacquinone + chitosan sample by gavage; Group E rats were given lacquinone + phospholipid sample by gavage. The dosage was as shown in Table 1, and the administration frequency was once. Before administration, rats were fasted but not allowed to drink for more than 12 hours.

[0103] 6.1.3 Blood collection method: Blood was collected from the orbital venous plexus. 0.5 mL of blood was collected from the orbital venous plexus before administration and at 5 min, 15 min, 30 min, 45 min, 60 min, 90 min, 150 min, 240 min, 8 h, and 12 h after administration. Heparin sodium was used for anticoagulation. The plasma was separated by centrifugation at 3000 r / min for 15 min and stored at -80℃.

[0104] 6.2 Determination of Sample Content

[0105] 6.2.1 Sample Pretreatment Method

[0106] Take 50 μL of plasma, add 200 μL of extraction buffer 1 (0.1% formic acid acetonitrile solution containing 10 ng / mL quercetin), vortex for 10 min, 4000 rpm.

[0107] Centrifuge for 10 minutes, take 200 μL of supernatant for LC-MS detection.

[0108] 6.2.2 Chromatographic conditions

[0109] Chromatographic column: ACQYUTYUPLCBEH C18 1.7μm, 50×2.1mm, Waters Technology (Shanghai) Co., Ltd.;

[0110] Column temperature: 40℃;

[0111] Mobile phase: A—water (containing 0.1% formic acid), B—acetonitrile (containing 0.1% formic acid)

[0112] Injection volume: 10 μL.

[0113] Table 2 Elution gradient

[0114]

[0115]

[0116] 6.2.3 Mass Spectrometry Conditions Mass spectrometry parameter settings The ion source gas used is high-purity (>99%) nitrogen.

[0117] Table 3 Mass Spectrometry Parameters

[0118]

[0119] VII. Data Processing

[0120] 7.1 Plotting Blood Drug Concentration-Time Curves

[0121] Experimental data were statistically processed using GraphPadPrism 10 biostatistics software, and quantitative data are expressed as mean ± SEM.

[0122] 7.2 Calculation of pharmacokinetic parameters

[0123] The pharmacokinetic parameters of the test samples were calculated using DAS software, and the main pharmacokinetic parameters were calculated using a non-compartmental model analysis.

[0124] 7.3 Statistical Analysis

[0125] Significance analysis was performed using SPSS 22.0 software, and independent samples t-tests were used to compare the two groups.

[0126] 7.4 Bioavailability Calculation

[0127] Using the data from intravenous and oral administration of flaxseed extract samples as a standard formulation, the absolute bioavailability of the four samples was calculated to compare the bioavailability of different samples.

[0128] VIII. Results and Analysis

[0129] 8.1 Standard Curve

[0130] A standard curve was plotted with the concentration of each target compound in the standard as the x-axis and the peak area as the y-axis. The linear regression equation and correlation coefficient of the standard curve are shown in the table below. All target compounds showed good linearity within the investigated concentration range, and the correlation coefficients (R2) of the linear regression equations were all above 0.99.

[0131]

[0132] 8.2 Data Quality Control

[0133] Quality control (QC) samples are mixed standards. The pretreatment method for QC samples is the same as for calibrators and test samples. One QC sample is interspersed with every 50 samples tested to assess the stability of the instrument during the testing process. The peak area ratio of each target compound and its corresponding internal standard in the QC sample is substituted into a linear regression equation to calculate the concentration of the target compound in the QC sample. The RSD% of all target compound concentrations in the QC sample must be less than 20%, and the deviation from the target value must be less than 15% to be considered a pass for data quality control.

[0134] Table 5 Data Quality Control Results

[0135]

[0136] 8.3 Blood drug concentration-time curve

[0137] See Figures 2-7 .

[0138] 8.4 Drug metabolism data results

[0139] The main pharmacokinetic parameters in this experiment are as follows:

[0140]

[0141]

[0142]

[0143] Note: *: using lacquer yellow as a control, *: P<0.05, **: P<0.01, ***: P<0.001, ****: P<0.0001

[0144] #: Using rutin + Ganoderma lucidum polysaccharide as a control, #: P<0.05, ##: P<0.01, ###: P<0.001, ####: P<0.0001

[0145] 8.5 Bioavailability Data Chart

[0146] Using laccasein as a control:

[0147] Figure 8 This is a comparison chart of Cmax values ​​for each group of samples. Figure 9 This is a comparison chart of the half-lives of each group of samples. Figure 10 This is a comparison chart of Tmax values ​​for each group of samples. Figure 11 This is a comparison chart of MRT (Mass Rapid Transit) devices; from Figure 9 It is evident that phospholipids reduced the Cmax of rutin while prolonging the time to peak concentration and half-life. Combined with MRT data, this suggests that phospholipids have a sustained-release effect on rutin, but may potentially reduce overall efficacy. The Ganoderma lucidum polysaccharide group showed a significant increase in Cmax, also significantly higher than the phospholipid group, but only a slight prolongation in half-life and Tmax. The remaining groups all increased the half-life and Tmax of rutin to some extent, but without significant difference.

[0148] Figure 12 This is a comparison chart of absolute bioavailability. Figure 13 The chart shows the comparison of relative bioavailability. In terms of absolute bioavailability, the groups were 2.87%, 21.88%, 29.13%, 6.84%, and 8.05%, respectively. In terms of relative bioavailability, the groups had multiples of 7.63, 10.16, 2.38, and 2.80, respectively. The Ganoderma lucidum polysaccharide group showed significant differences from all other groups.

[0149] 8.6 Bioavailability Calculation

[0150] 1. Absolute bioavailability (calculated based on intravenous administration data):

[0151] For the flavonoid (98%) sample: F(abs) = (AUCpo·Div) / (AUCiv·Dpo) × 100% = 2.87 ± 0.86%

[0152] Oxalis + Gum Arabic: F(abs) = (AUCpo·Div) / (AUCiv·Dpo) × 100% = 21.88 ± 4.97%

[0153] Rhubarb + Ganoderma lucidum polysaccharide: F(abs)=(AUCpo·Div / (AUCiv·Dpo)×100%=29.13±8.33%

[0154] Rhus xanthophyll + chitosan: F(abs) = (AUCpo·Div) / (AUCiv·Dpo) × 100% = 6.84 ± 2.65%

[0155] Rhubarb + Phospholipid: F(abs) = (AUCpo·Div) / (AUCiv·Dpo) × 100% = 8.05 ± 1.64%

[0156] 2. Using the flavonoid (98%) sample as the standard reference preparation, the relative bioavailability of the other preparations is as follows:

[0157] AUCpo laccasein + arabinogelatin: F' = (AUCpo laccasein + arabinogelatin) / (AUCpo laccasein)

[0158] (Number of elements) × 100% = 763.48 ± 178.09%

[0159] Rhubarb + Ganoderma lucidum polysaccharide: F'=(AUCpoRhubarb + Ganoderma lucidum polysaccharide) / (AUCpoRhubarb)

[0160] (Number of elements) × 100% = 1016.50 ± 296.98%

[0161] Rhubarb + Chitosan: F' = (AUCpo Rhubarb + Ganoderma lucidum polysaccharide) / (AUCpo Rhubarb)

[0162] (Number of elements) × 100% = 238.76 ± 90.59%

[0163] Rhubarb + Phospholipid: F' = (AUCpo rhubarb + Phospholipid · Dpo rhubarb) / (AUCpo rhubarb · Dpo rhubarb + Phospholipid) × 100% = 280.79 ± 65.20%

[0164] Note: AUCpo: Area under the curve for oral administration (AUC(0-t); AUCiv: Area under the curve for intravenous administration (AUC(0-t); Div: Intravenous dose; Dpo: Oral dose.

Claims

1. A composition of Ganoderma lucidum polysaccharide and rutin, characterized in that: The weight ratio of Ganoderma lucidum polysaccharide to laccasein is 18-40:10-30.

2. The composition according to claim 1, characterized in that: The composition is a Ganoderma lucidum polysaccharide inclusion complex of rutin.

3. The composition according to claim 1, characterized in that, Its preparation method includes the following steps: Take Ganoderma lucidum polysaccharide, rutin, and deionized water equivalent to 3-10 times the weight of Ganoderma lucidum polysaccharide, grind and mix them, then filter and mix them through a 200-800um microfluidic chip, then freeze-dry them, and then pulverize the freeze-dried product and pass it through a 200-800 mesh sieve to obtain the final product.

4. The composition according to claim 3, characterized in that: The grinding and mixing are carried out in a high-energy ball mill, with the temperature controlled at 25-40℃.

5. The composition according to claim 3, characterized in that: The freeze-drying time is 24-48 hours.

6. Uses of Ganoderma lucidum polysaccharides in improving the bioavailability of rutin.

7. The use of the combination of Ganoderma lucidum polysaccharide and rutin in the preparation of anti-aging drugs, health products, or food.

8. The use of the combination of Ganoderma lucidum polysaccharide and rutin in the preparation of products that improve skin condition, soothe skin, repair skin, tighten skin, whiten skin, or reduce wrinkles.

9. The use of the combination of Ganoderma lucidum polysaccharide and rutin in the preparation of medicines, health products or foods for the treatment and / or prevention of osteoarthritis and osteoporosis.

10. The use of the combination of Ganoderma lucidum polysaccharide and rutin in the preparation of medicines, health products, or foods for the treatment and / or prevention of neurodegenerative diseases.

11. The use of the combination of Ganoderma lucidum polysaccharide and rutin in the preparation of anti-inflammatory drugs, health products, or food.

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