Medicinal oral liquid of glycosaminoglycan and preparation method thereof

Abstract

The invention relates to medicinal oral liquid of glycosaminoglycan and a preparation method, and belongs to the technical field of biological medicines.The oral liquid adopts glycosaminoglycan-rich collagen peptide, cod collagen oligopeptide powder, skipjack elastin peptide-Y, fish maw oligopeptide powder, fish collagen tripeptide, apple concentrated juice, white birch juice and the like as effective active ingredients, the apple concentrated juice is obtained by sequentially carrying out step-by-step enzymolysis on green apples through bromelain, ficin and trypsin; the white birch juice is obtained by carrying out anaerobic fermentation on white birch juice through lactobacillus brevis and lactobacillus cellosus. All the components are matched for use, so that the food has very good effects of reducing blood fat, increasing bone mineral density, improving immunity, resisting fatigue and the like, and the action effect is rapid and effective.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to a medicinal oral liquid of glycosaminoglycans and its preparation method. Background Technology

[0002] With the improvement of people's living standards and changes in lifestyle, the incidence of chronic diseases is gradually increasing, such as hyperlipidemia, osteoporosis, low immunity and chronic fatigue syndrome, which seriously affect people's quality of life and health.

[0003] Dyslipidemia is a significant risk factor for cardiovascular disease. In modern society, high-calorie, high-fat diets and unhealthy lifestyle habits such as lack of exercise have led to a continuous increase in the number of patients with hyperlipidemia. Long-term hyperlipidemia accelerates the progression of atherosclerosis and increases the risk of cardiovascular diseases such as myocardial infarction and stroke. While commonly used lipid-lowering drugs can control blood lipid levels to some extent, they often have problems such as significant side effects and unstable efficacy.

[0004] Decreased bone density is a serious problem facing an aging society. With age and improper diet, the body's bone metabolism becomes unbalanced, with bone resorption exceeding bone formation, leading to a gradual decline in bone density and increasing the risk of osteoporosis. Osteoporosis not only causes bone pain and fractures, but also increases the disability and mortality rates of patients. Traditional treatments, such as calcium and vitamin D supplementation, have limited effectiveness and cannot fundamentally solve the problem of decreased bone density.

[0005] Immunity is a crucial defense mechanism for the body against disease. Under the influence of factors such as stress, environmental pollution, and poor diet, the body's immune system is prone to dysfunction, leading to decreased immunity and increasing the risk of infections, tumors, and other diseases. Currently, methods to improve immunity mainly include a balanced diet, moderate exercise, and sufficient sleep. However, for some individuals with severely weakened immunity, these methods are often insufficient to quickly and effectively improve immune function.

[0006] Fatigue is a common symptom. High stress levels, long hours of work, and other factors can all lead to fatigue. Chronic fatigue can seriously impact physical and mental health. The fast pace of modern life, high-intensity work, and psychological stress are causing more and more people to feel exhausted. Current methods for relieving fatigue mainly include rest and lifestyle adjustments, but these methods are often ineffective for fatigue caused by physiological dysfunction.

[0007] Therefore, targeted treatment of various symptoms is necessary using health supplements or biological drugs. With the rapid development of biotechnology, an increasing number of biological drugs have been developed, providing new options for treating various diseases. Biological drugs have also shown great potential in lowering blood lipids, increasing bone density, enhancing immunity, and combating fatigue. For example, certain bioactive peptides can lower blood cholesterol and triglyceride levels by regulating the activity of enzymes related to lipid metabolism; some active factors can promote the proliferation and differentiation of bone cells, increasing bone density; certain proteins can enhance the body's immune response and improve immunity; and certain biomolecules with antioxidant effects can scavenge free radicals in the body, reducing oxidative stress damage, thereby achieving anti-fatigue effects.

[0008] However, research on biological drugs that lower blood lipids, increase bone density, enhance immunity, and combat fatigue is still in its early stages, with varying efficacy and the speed and effectiveness of their effects needing further improvement. Therefore, continued in-depth development, improvement, and optimization of drug components and preparation processes are necessary to enhance both efficacy and safety. Summary of the Invention

[0009] The existing biological drugs exhibit inconsistent efficacy in lowering blood lipids, increasing bone density, enhancing immunity, and combating fatigue, and their rapid and effective effects require further improvement. This invention provides a glycosaminoglycan-based oral liquid and its preparation method. The oral liquid uses glycosaminoglycan-rich collagen peptides, cod collagen oligopeptide powder, bonito elastin peptide-Y, fish maw oligopeptide powder, fish collagen tripeptide, apple concentrate, and birch sap as active ingredients. The apple concentrate is obtained by sequentially hydrolyzing green apples with bromelain, figase, and trypsin. The birch sap is obtained through anaerobic fermentation of birch sap with *Lactobacillus brevis* and *Lactobacillus fibrinolyticus*. The combined effects of these ingredients effectively lower blood lipids, increase bone density, enhance immunity, and combat fatigue, with rapid and effective results. The specific technical solution is as follows:

[0010] A medicinal oral liquid of glycosaminoglycans, comprising the following raw materials in parts by weight: 1-5 parts glycosaminoglycan-rich collagen peptides, 1-5 parts cod collagen oligopeptide powder, 1-5 parts bonito elastin peptide-Y, 1-5 parts fish maw oligopeptide powder, 1-10 parts fish collagen tripeptide, 0.1-1 part vitamin C, 1-10 parts apple concentrate, 0.1-1 part citric acid, 0.5-1 part erythritol, 0.01-0.1 parts food flavoring, 30-90 parts birch sap, and 20-40 parts purified water; wherein the apple concentrate is obtained by sequentially enzymatically hydrolyzing green apples with bromelain, figase, and trypsin, followed by concentration; and the birch sap is obtained by anaerobic fermentation of birch sap with Lactobacillus brevis and Lactobacillus fibrinolyticus.

[0011] In the above technical solution, the glycosaminoglycan-rich collagen peptide has a glycosaminoglycan content of 32wt% to 42wt%.

[0012] In the above technical solution, the total nitrogen content of the cod collagen oligopeptide powder is ≥15wt%.

[0013] In the above technical solution, the total content of desmokine and isodesmokine of the skipjack tuna elastin peptide-Y is ≥0.2wt%.

[0014] In the above technical solution, the oligopeptide content of the fish maw oligopeptide powder is ≥75.0wt%.

[0015] The method for preparing apple concentrate in the above technical solution includes the following steps: crush green apples, add 4 to 6 times the weight of the green apples in water, mix, adjust the pH to 6.8 to 7.2, then add 0.5% to 1.5% of the weight of the green apples in bromelain, hydrolyze at 50℃ to 60℃ for 1.5 to 2 hours, inactivate the enzyme at high temperature, cool to room temperature, add 0.5% to 1.5% of the weight of the green apples in fig protease, hydrolyze at 60℃ to 65℃ for 1 to 1.5 hours, inactivate the enzyme at high temperature, cool to room temperature, adjust the pH to 7.8 to 8.5, add 0.5% to 1% of the weight of protein in trypsin, hydrolyze at 35℃ to 38℃ for 1 to 1.5 hours, inactivate the enzyme at high temperature, cool to room temperature, adjust the pH to 6.8 to 7.2, filter using a sieve to obtain apple juice, concentrate to 15% to 25% of the volume, and obtain apple concentrate.

[0016] The bromelain has an enzyme activity of 100,000 U / g; the fig protease has an enzyme activity of 100,000 U / g; the trypsin has an enzyme activity of 100,000 U / g; the high-temperature enzyme inactivation temperature is 90℃~90℃.

[0017] The temperature is 5℃, and the time is 15 min to 20 min; the mesh size of the sieve is 325 mesh to 500 mesh.

[0018] The above technical solution includes the following steps for preparing birch sap: collecting birch sap, filtering it through a 200-250 mesh sieve to remove impurities and suspended matter, adding 1%-5% glucose, 0.5%-1.5% peptone, and 0.05%-0.1% potassium chloride by weight of birch sap, then adding 0.3%-0.8% Lactobacillus brevis and 0.3%-0.8% Lactobacillus fibrinolyticus by weight of birch sap, anaerobic fermentation for 20-30 hours, high-temperature sterilization, and filtering through a 325-500 mesh sieve to obtain birch sap.

[0019] The viability of the *Lactobacillus brevis* is 100 million CFU / g; the viability of the *Lactobacillus fibrinolyticus* is 100 million CFU / g; the high-temperature sterilization temperature is 121℃~125℃, and the time is 15min~20min.

[0020] The preparation method of the above-mentioned glycosaminoglycan oral liquid includes the following steps:

[0021] According to the mass fraction ratio, heat purified water to 60℃~65℃, then add cod collagen oligopeptide powder, fish collagen tripeptide, erythritol, glycosaminoglycan collagen peptide, bonito elastin peptide-Y, fish maw oligopeptide powder, vitamin C, and citric acid in sequence, and stir until well mixed. Then add apple concentrate and stir until well mixed. Next, add food flavoring and stir until well mixed. Finally, add birch sap to make up the volume, filter through a 200-250 mesh sieve, bottle and seal, and microwave sterilize to obtain oral liquid.

[0022] In the above preparation method, the microwave sterilization temperature is above 80°C and the frequency is 2450 MHz.

[0023] The glycosaminoglycan oral liquid prepared by the above preparation method can be used to formulate oral liquids with the effects of lowering blood lipids, increasing bone density, improving immunity and anti-fatigue; it can be prepared and used directly, or after dilution, or after concentration.

[0024] The present invention provides a pharmaceutical oral liquid of glycosaminoglycans and its preparation method, which, compared with the prior art, have the following advantages:

[0025] I. The oral liquid of this invention contains active ingredients such as glycosaminoglycan collagen peptides, cod collagen oligopeptide powder, bonito elastin peptide-Y, fish maw oligopeptide powder, fish collagen tripeptide, apple concentrate, and birch sap. The combination of these ingredients has a good effect on lowering blood lipids, increasing bone density, improving immunity, and anti-fatigue, with rapid and effective results.

[0026] II. Glycosamine-rich collagen peptides contain 32wt%–42wt% glycosamines. These peptides increase the thickness and resilience of articular cartilage, increase bone density, promote digestive health, enhance immunity, regulate the endocrine system, relieve stress and anxiety, improve sleep quality, and boost energy levels, thus combating fatigue. Furthermore, glycosamines lower blood lipid levels, reduce the risk of atherosclerosis, improve vascular flexibility and elasticity, and maintain normal blood pressure.

[0027] Third, cod collagen oligopeptide powder can maintain skin health, delay skin aging, enhance bone health, increase bone density, accelerate wound healing, promote the repair and regeneration of damaged tissues, and also has good effects such as lowering blood lipids, improving immunity, improving sleep quality and anti-fatigue.

[0028] IV. Skipjack tuna elastin peptide-Y is a protein peptide extracted from the bulbus arteriosus of the skipjack tuna heart.

[0029] It helps maintain skin elasticity and firmness, reduces wrinkles and sagging, is beneficial to the health of joints and connective tissues, and can enhance their toughness and flexibility. It also has certain effects on lowering blood lipids, increasing bone density, improving immunity, and anti-fatigue.

[0030] V. Glycosamine-rich collagen peptides, cod collagen oligopeptide powder, and bonito elastin peptide-Y all have the effects of lowering blood lipids, increasing bone density, improving immunity, and anti-fatigue. When used in combination in a certain proportion, the three can exert outstanding therapeutic effects, with rapid and effective results.

[0031] VI. Fish maw oligopeptide powder has nourishing and beautifying effects, helping to improve skin moisture and elasticity, reduce wrinkles, and make skin smoother and firmer. It also enhances immunity, providing nutrients to the body and helping to improve resistance and strengthen the immune system. Furthermore, it nourishes blood, improves pale complexion, and combats fatigue. Finally, it helps maintain the health of joint cartilage and accelerates tissue regeneration and repair.

[0032] 7. Fish collagen tripeptide has the effect of repairing tissues. It can promote the synthesis of bone collagen, enhance the strength and toughness of bones, prevent osteoporosis and other problems, improve joint function, maintain the normal structure and function of articular cartilage, improve joint mobility, lower blood lipids, enhance vascular elasticity, and improve vascular function.

[0033] 8. The apple concentrate of this invention is obtained by sequentially enzymatically hydrolyzing green apples with bromelain, figase, and trypsin, followed by concentration. The apple concentrate prepared by this method contains various enzymatically hydrolyzed small molecule peptides and other active nutrients, exhibiting significant effects in lowering blood lipids, enhancing immunity, and combating fatigue, with rapid and effective results.

[0034] 9. The birch sap of this invention is obtained by anaerobic fermentation of birch sap with Lactobacillus brevis and Lactobacillus fibrinolyticus. Birch sap contains fermentation products of Lactobacillus brevis and Lactobacillus fibrinolyticus, as well as other active nutrients, and has outstanding effects in lowering blood lipids, improving immunity, and combating fatigue, with rapid and effective results. Detailed Implementation

[0035] The present invention will be further described below with reference to specific implementation examples, but the present invention is not limited to these embodiments.

[0036] Example 1

[0037] A medicinal oral liquid of glycosaminoglycans, the oral liquid being made from the following raw materials in parts by weight: 3 parts glycosaminoglycan-rich collagen peptides, 3 parts cod collagen oligopeptide powder, 3 parts bonito elastin peptide-Y, 3 parts fish maw oligopeptide powder, 5 parts fish collagen tripeptide, 0.5 parts vitamin C, 5 parts apple concentrate, 0.5 parts citric acid, 0.8 parts erythritol, 0.05 parts food flavoring, 60 parts birch sap, and 30 parts purified water.

[0038] The preparation method of apple concentrate includes the following steps: Green apples are crushed, then water (4 times the weight of the green apples) is added and mixed. The pH is adjusted to 6.8. Then, 0.5% (by weight of the green apples) of bromelain with an activity of 100,000 U / g is added. The mixture is hydrolyzed at 50℃ for 1.5 hours, and then inactivated at 90℃ for 15 minutes. After cooling to room temperature, 0.5% (by weight of the green apples) of fig protease with an activity of 100,000 U / g is added. The mixture is hydrolyzed at 60℃ for 1 hour, and then inactivated at 90℃ for 15 minutes. After cooling to room temperature, the pH is adjusted to 7.8. Then, 0.5% (by weight of the protein) of trypsin with an activity of 100,000 U / g is added. The mixture is hydrolyzed at 35℃ for 1 hour, and then inactivated at 90℃ for 15 minutes. After cooling to room temperature, the pH is adjusted to 6.8. The mixture is filtered through a 325-mesh sieve to obtain apple juice. The juice is then concentrated to 15% of its volume to obtain apple concentrate.

[0039] The preparation method of birch sap includes the following steps: collecting birch sap, filtering it through a 200-mesh sieve to remove impurities and suspended matter, adding 1% glucose, 0.5% peptone, and 0.05% potassium chloride by weight of birch sap, then adding 0.3% Lactobacillus brevis with a bacterial activity of 100 million CFU / g and 0.3% Lactobacillus fibrinolyticus with a bacterial activity of 100 million CFU / g by weight of birch sap, anaerobic fermentation for 20 hours, high-temperature sterilization at 121℃ for 15 minutes, and filtering through a 325-mesh sieve to obtain birch sap.

[0040] The preparation method of the above-mentioned glycosaminoglycan oral liquid includes the following steps:

[0041] According to the mass fraction ratio, heat purified water to 60℃, then add cod collagen oligopeptide powder, fish collagen tripeptide, erythritol, glycosaminoglycan collagen peptide, bonito elastin peptide-Y, fish maw oligopeptide powder, vitamin C, and citric acid in sequence, and stir until well mixed. Then add apple concentrate and stir until well mixed. Next, add food flavoring and stir until well mixed. Finally, add birch sap to make up the volume, filter through a 200-mesh sieve, bottle and seal, and microwave sterilize to obtain oral liquid.

[0042] In this embodiment, the oral liquid is sterilized by microwave at a temperature of 80°C, a frequency of 2450MHz, and a time of 5 minutes.

[0043] The supplier of the glycosaminoglycan-rich collagen peptides in this embodiment is ABYSS INGREDIENTS, and the glycosaminoglycan content of the glycosaminoglycan-rich collagen peptides is 32 wt%. The supplier of cod collagen oligopeptide powder is Hainan Huayan Collagen Technology Co., Ltd., and the total nitrogen content of the cod collagen oligopeptide powder is 15 wt%. The supplier of skipjack tuna elastin peptide-Y is COPAL ISI NDUSTRI E, and the total content of desmokine and isodesmokine in skipjack tuna elastin peptide-Y is 0.2 wt%. The supplier of fish maw oligopeptide powder is Dalian Shenlan Peptide Technology R&D Co., Ltd., and the oligopeptide content of the fish maw oligopeptide powder is 75.0 wt%. The supplier of fish collagen tripeptide is Xiamen Yuanzhidao Biotechnology Co., Ltd., and the fish collagen tripeptide content is 86.93 wt%.

[0044] Example 2

[0045] A medicinal oral liquid of glycosaminoglycans, the oral liquid being made from the following raw materials in parts by weight: 1 part glycosaminoglycan-rich collagen peptide, 1 part cod collagen oligopeptide powder, 1 part bonito elastin peptide-Y, 1 part fish maw oligopeptide powder, 1 part fish collagen tripeptide, 0.1 part vitamin C, 1 part apple concentrate, 0.1 part citric acid, 0.5 part erythritol, 0.01 part food flavoring, 30 parts birch sap, and 20 parts purified water.

[0046] The preparation method of apple concentrate includes the following steps: Green apples are crushed, then 4.5 times their weight in water is added and mixed. The pH is adjusted to 6.9. Then, 0.8% (by weight of the green apples) of bromelain with an activity of 100,000 U / g is added. The mixture is hydrolyzed at 52℃ for 1.5 hours, and then inactivated at 92℃ for 16 minutes. After cooling to room temperature, 0.8% (by weight of the green apples) of fig protease with an activity of 100,000 U / g is added. The mixture is hydrolyzed at 62℃ for 1 hour, and then inactivated at 92℃ for 16 minutes. After cooling to room temperature, the pH is adjusted to 8. Then, 0.6% (by weight of the protein) of trypsin with an activity of 100,000 U / g is added. The mixture is hydrolyzed at 36℃ for 1 hour, and then inactivated at 92℃ for 16 minutes. After cooling to room temperature, the pH is adjusted to 6.9. The mixture is filtered through a 325-mesh sieve to obtain apple juice. The juice is then concentrated to 18% of its volume to obtain apple concentrate.

[0047] The preparation method of birch sap includes the following steps: collecting birch sap, filtering it through a 200-mesh sieve to remove impurities and suspended matter, adding 2% glucose, 0.8% peptone, and 0.06% potassium chloride by weight of birch sap, then adding 0.4% Lactobacillus brevis with a bacterial activity of 100 million CFU / g and 0.4% Lactobacillus fibrinolyticus with a bacterial activity of 100 million CFU / g by weight of birch sap, anaerobic fermentation for 22 hours, high-temperature sterilization at 122℃ for 16 minutes, and filtering through a 325-mesh sieve to obtain birch sap.

[0048] The preparation method of the above-mentioned glycosaminoglycan oral liquid includes the following steps:

[0049] According to the mass fraction ratio, heat purified water to 62℃, then add cod collagen oligopeptide powder, fish collagen tripeptide, erythritol, glycosaminoglycan collagen peptide, bonito elastin peptide-Y, fish maw oligopeptide powder, vitamin C, and citric acid in sequence, and stir until well mixed. Then add apple concentrate and stir until well mixed. Next, add food flavoring and stir until well mixed. Finally, add birch sap to make up the volume, filter through a 200-mesh sieve, bottle and seal, and microwave sterilize to obtain the oral liquid.

[0050] In this embodiment, the temperature for microwave sterilization of the oral liquid is 82°C, the frequency is 2450MHz, and the time is 8 minutes.

[0051] The supplier of the glycosaminoglycan-rich collagen peptides in this embodiment is ABYSS I NGREDI ENTS, and the glycosaminoglycan content of the glycosaminoglycan-rich collagen peptides is 35 wt%. The supplier of cod collagen oligopeptide powder is Hainan Huayan Collagen Technology Co., Ltd., and the total nitrogen content of the cod collagen oligopeptide powder is 16 wt%. The supplier of skipjack tuna elastin peptide-Y is COPALI SI NDUSTRI E, and the total content of desmokine and isodesmokine in skipjack tuna elastin peptide-Y is 0.22 wt%. The supplier of fish maw oligopeptide powder is Dalian Shenlan Peptide Technology R&D Co., Ltd., and the oligopeptide content of the fish maw oligopeptide powder is 76 wt%. The supplier of fish collagen tripeptide is Xiamen Yuanzhidao Biotechnology Co., Ltd., and the fish collagen tripeptide content is 87.02 wt%.

[0052] Example 3

[0053] A medicinal oral liquid of glycosaminoglycans, the oral liquid being made from the following raw materials in parts by weight: 2 parts glycosaminoglycan-rich collagen peptides, 2 parts cod collagen oligopeptide powder, 2 parts bonito elastin peptide-Y, 2 parts fish maw oligopeptide powder, 3 parts fish collagen tripeptide, 0.3 parts vitamin C, 3 parts apple concentrate, 0.3 parts citric acid, 0.7 parts erythritol, 0.03 parts food flavoring, 40 parts birch sap, and 25 parts purified water.

[0054] The preparation method of apple concentrate includes the following steps: Green apples are crushed, then water with a mass equal to 5 times the weight of the green apples is added and mixed. The pH is adjusted to 7. Then, 1% (by weight of the green apples) of bromelain with an enzyme activity of 100,000 U / g is added, and the mixture is hydrolyzed at 55℃ for 1.5 hours, followed by enzyme inactivation at 93℃ for 18 minutes. After cooling to room temperature, 1% (by weight of the green apples) of fig protease with an enzyme activity of 100,000 U / g is added, and the mixture is hydrolyzed at 63℃ for 1 hour, followed by enzyme inactivation at 93℃ for 18 minutes. After cooling to room temperature, the pH is adjusted to 8.2. 0.8% (by weight of protein) of trypsin with an enzyme activity of 100,000 U / g is added, and the mixture is hydrolyzed at 37℃ for 1 hour, followed by enzyme inactivation at 93℃ for 18 minutes. After cooling to room temperature, the pH is adjusted to 7. The mixture is then filtered through a 325-mesh sieve to obtain apple juice. The juice is then concentrated to 20% of its volume to obtain apple concentrate.

[0055] The preparation method of birch sap includes the following steps: collecting birch sap, filtering it through a 200-mesh sieve to remove impurities and suspended matter, adding 3% glucose, 1% peptone, and 0.08% potassium chloride by weight of birch sap, then adding 0.5% Lactobacillus brevis with a bacterial activity of 100 million CFU / g and 0.5% Lactobacillus fibrinolyticus with a bacterial activity of 100 million CFU / g by weight of birch sap, anaerobic fermentation for 25 hours, high-temperature sterilization at 124℃ for 18 minutes, and filtering through a 325-mesh sieve to obtain birch sap.

[0056] The preparation method of the above-mentioned glycosaminoglycan oral liquid includes the following steps:

[0057] According to the mass fraction ratio, purified water is heated to 63°C, and then cod collagen oligopeptide powder, fish collagen tripeptide, erythritol, glycosaminoglycan collagen peptide, bonito elastin peptide-Y, fish maw oligopeptide powder, vitamin C, and citric acid are added in sequence. The mixture is stirred and mixed evenly. Then, apple concentrate is added and stirred and mixed evenly. Next, food flavoring is added and stirred and mixed evenly. Finally, birch sap is added to make up the volume. The mixture is filtered through a 200-mesh sieve, bottled and sealed, and microwaved to obtain the oral liquid.

[0058] In this embodiment, the oral liquid was microwave sterilized at a temperature of 85°C, a frequency of 2450MHz, and a time of 10 minutes.

[0059] The supplier of the glycosaminoglycan-rich collagen peptides in this embodiment is ABYSS I NGREDI ENTS, and the glycosaminoglycan content of the glycosaminoglycan-rich collagen peptides is 37 wt%. The supplier of cod collagen oligopeptide powder is Hainan Huayan Collagen Technology Co., Ltd., and the total nitrogen content of the cod collagen oligopeptide powder is 16.2 wt%. The supplier of skipjack tuna elastin peptide-Y is COPALI SI NDUSTRI E, and the total content of desmokine and isodesmokine in skipjack tuna elastin peptide-Y is 0.3 wt%. The supplier of fish maw oligopeptide powder is Dalian Shenlan Peptide Technology R&D Co., Ltd., and the oligopeptide content of the fish maw oligopeptide powder is 76.8 wt%. The supplier of fish collagen tripeptide is Xiamen Yuanzhidao Biotechnology Co., Ltd., and the fish collagen tripeptide content is 87.43 wt%.

[0060] Example 4

[0061] A medicinal oral liquid of glycosaminoglycans, the oral liquid being made from the following raw materials in parts by weight: 4 parts glycosaminoglycan-rich collagen peptides, 4 parts cod collagen oligopeptide powder, 4 parts bonito elastin peptide-Y, 4 parts fish maw oligopeptide powder, 8 parts fish collagen tripeptide, 0.8 parts vitamin C, 8 parts apple concentrate, 0.8 parts citric acid, 0.8 parts erythritol, 0.08 parts food flavoring, 75 parts birch sap, and 35 parts purified water.

[0062] The preparation method of apple concentrate includes the following steps: Green apples are crushed, then water (5.5 times the weight of the green apples) is added and mixed. The pH is adjusted to 7.1. Then, 1.2% (by weight of the green apples) of bromelain with an enzyme activity of 100,000 U / g is added. The mixture is hydrolyzed at 58℃ for 2 hours, and then inactivated at 94℃ for 18 minutes. After cooling to room temperature, 1.2% (by weight of the green apples) of fig protease with an enzyme activity of 100,000 U / g is added. The mixture is hydrolyzed at 62℃ for 1.5 hours, and then inactivated at 94℃ for 18 minutes. After cooling to room temperature, the pH is adjusted to 8.4. Then, 0.8% (by weight of protein) of trypsin with an enzyme activity of 100,000 U / g is added. The mixture is hydrolyzed at 37℃ for 1.5 hours, and then inactivated at 94℃ for 18 minutes. After cooling to room temperature, the pH is adjusted to 7.1. The mixture is filtered through a 500-mesh sieve to obtain apple juice. The juice is then concentrated to 23% of its volume to obtain apple concentrate.

[0063] The preparation method of birch sap includes the following steps: collecting birch sap, filtering it through a 250-mesh sieve to remove impurities and suspended solids, adding 4% glucose, 1.2% peptone, and 0.08% potassium chloride by weight of birch sap, then adding 0.7% Lactobacillus brevis with a bacterial activity of 100 million CFU / g and 0.7% Lactobacillus fibrinolyticus with a bacterial activity of 100 million CFU / g by weight of birch sap, anaerobic fermentation for 28 hours, high-temperature sterilization at 125℃ for 18 minutes, and filtering through a 500-mesh sieve to obtain birch sap.

[0064] The preparation method of the above-mentioned glycosaminoglycan oral liquid includes the following steps:

[0065] According to the mass fraction ratio, purified water is heated to 64℃, and then cod collagen oligopeptide powder, fish collagen tripeptide, erythritol, glycosaminoglycan collagen peptide, bonito elastin peptide-Y, fish maw oligopeptide powder, vitamin C, and citric acid are added in sequence. The mixture is stirred and mixed evenly. Then, apple concentrate is added and stirred and mixed evenly. Next, food flavoring is added and stirred and mixed evenly. Finally, birch sap is added to make up the volume. The mixture is filtered through a 250-mesh sieve, bottled and sealed, and microwaved to obtain the oral liquid.

[0066] In this embodiment, the oral liquid was microwave sterilized at a temperature of 88°C, a frequency of 2450MHz, and a time of 12 minutes.

[0067] The supplier of the glycosaminoglycan-rich collagen peptides in this embodiment is ABYSS INGREDIENTS, and the glycosaminoglycan content of the glycosaminoglycan-rich collagen peptides is 40 wt%. The supplier of cod collagen oligopeptide powder is Hainan Huayan Collagen Technology Co., Ltd., and the total nitrogen content of the cod collagen oligopeptide powder is 17.3 wt%. The supplier of skipjack tuna elastin peptide-Y is COPAL ISI NDUSTRI E, and the total content of desmokine and isodesmokine in skipjack tuna elastin peptide-Y is 0.36 wt%. The supplier of fish maw oligopeptide powder is Dalian Shenlan Peptide Technology R&D Co., Ltd., and the oligopeptide content of the fish maw oligopeptide powder is 76.8 wt%. The supplier of fish collagen tripeptide is Xiamen Yuanzhidao Biotechnology Co., Ltd., and the fish collagen tripeptide content is 88.45 wt%.

[0068] Example 5

[0069] A medicinal oral liquid of glycosaminoglycans, the oral liquid being made from the following raw materials in parts by weight: 5 parts glycosaminoglycan-rich collagen peptides, 5 parts cod collagen oligopeptide powder, 5 parts bonito elastin peptide-Y, 5 parts fish maw oligopeptide powder, 10 parts fish collagen tripeptide, 1 part vitamin C, 10 parts apple concentrated juice, 1 part citric acid, 1 part erythritol, 0.1 part food flavoring, 90 parts birch sap, and 40 parts purified water.

[0070] The preparation method of apple concentrate includes the following steps: Green apples are crushed, then water (6 times the weight of the green apples) is added and mixed. The pH is adjusted to 7.2. Then, 1.5% (by weight of the green apples) of bromelain with an activity of 100,000 U / g is added. The mixture is hydrolyzed at 60℃ for 2 hours, and then inactivated at 95℃ for 20 minutes. After cooling to room temperature, 1.5% (by weight of the green apples) of fig protease with an activity of 100,000 U / g is added. The mixture is hydrolyzed at 65℃ for 1.5 hours, and then inactivated at 95℃ for 20 minutes. After cooling to room temperature, the pH is adjusted to 8.5. Then, 1% (by weight of protein) of trypsin with an activity of 100,000 U / g is added. The mixture is hydrolyzed at 38℃ for 1.5 hours, and then inactivated at 95℃ for 20 minutes. After cooling to room temperature, the pH is adjusted to 7.2. The mixture is filtered through a 500-mesh sieve to obtain apple juice. The juice is then concentrated to 25% of its volume to obtain apple concentrate.

[0071] The preparation method of birch sap includes the following steps: collecting birch sap, filtering it through a 250-mesh sieve to remove impurities and suspended matter, adding 5% glucose, 1.5% peptone, and 0.1% potassium chloride by weight of birch sap, then adding 0.8% Lactobacillus brevis with a bacterial activity of 100 million CFU / g and 0.8% Lactobacillus fibrinolyticus with a bacterial activity of 100 million CFU / g by weight of birch sap, anaerobic fermentation for 30 hours, high-temperature sterilization at 125℃ for 20 minutes, and filtering through a 500-mesh sieve to obtain birch sap.

[0072] The preparation method of the above-mentioned glycosaminoglycan oral liquid includes the following steps:

[0073] According to the mass fraction ratio, heat purified water to 65℃, then add cod collagen oligopeptide powder, fish collagen tripeptide, erythritol, glycosaminoglycan collagen peptide, bonito elastin peptide-Y, fish maw oligopeptide powder, vitamin C, and citric acid in sequence, and stir until well mixed. Then add apple concentrate and stir until well mixed. Next, add food flavoring and stir until well mixed. Finally, add birch sap to make up the volume, filter through a 250-mesh sieve, bottle and seal, and microwave sterilize to obtain oral liquid.

[0074] In this embodiment, the oral liquid is sterilized by microwave at a temperature of 90°C, a frequency of 2450MHz, and a time of 15 minutes.

[0075] The supplier of the glycosaminoglycan-rich collagen peptides in this embodiment is ABYSS INGREDIENTS, and the glycosaminoglycan content of the glycosaminoglycan-rich collagen peptides is 42 wt%. The supplier of cod collagen oligopeptide powder is Hainan Huayan Collagen Technology Co., Ltd., and the total nitrogen content of the cod collagen oligopeptide powder is 17.8 wt%. The supplier of skipjack tuna elastin peptide-Y is COPAL ISI NDUSTRI E, and the total content of desmokine and isodesmokine in skipjack tuna elastin peptide-Y is 0.34 wt%. The supplier of fish maw oligopeptide powder is Dalian Shenlan Peptide Technology R&D Co., Ltd., and the oligopeptide content of the fish maw oligopeptide powder is 76.5 wt%. The supplier of fish collagen tripeptide is Xiamen Yuanzhidao Biotechnology Co., Ltd., and the fish collagen tripeptide content is 88.43 wt%.

[0076] Comparative Example 1

[0077] The oral liquid does not contain glycosaminoglycan collagen peptides; the glycosaminoglycan collagen peptides are replaced by purified water. Other parameters and methods are the same as in Example 1.

[0078] Comparative Example 2

[0079] The oral liquid does not contain cod collagen oligopeptide powder; the cod collagen oligopeptide powder component is replaced by purified water. Other parameters and methods are the same as in Example 1.

[0080] Comparative Example 3

[0081] The oral liquid does not contain bonito elastin peptide-Y; instead, purified water is used to replace bonito elastin peptide-Y. Other parameters and methods are the same as in Example 1.

[0082] Comparative Example 4

[0083] The oral liquid does not contain glycosaminoglycan collagen peptides, cod collagen oligopeptide powder, or bonito elastin peptide-Y. The glycosaminoglycan collagen peptides, cod collagen oligopeptide powder, and bonito elastin peptide-Y are replaced with purified water. Other parameters and methods are the same as in Example 1.

[0084] Comparative Example 5

[0085] In the preparation method of apple concentrate, figase and trypsin hydrolysis are not performed; other parameters and methods are the same as in Example 1.

[0086] Comparative Example 6

[0087] In the preparation method of apple concentrate, fig protease hydrolysis is not performed; other parameters and methods are the same as in Example 1.

[0088] Comparative Example 7

[0089] The method for preparing birch sap is as follows: collect birch sap, filter it through a 200-mesh sieve to remove impurities and suspended solids, and obtain birch sap. Other parameters and methods are the same as in Example 1.

[0090] Comparative Example 8

[0091] In the preparation method of birch sap, no Lactobacillus cellulose is added for fermentation; other parameters and methods are the same as in Example 1.

[0092] The efficacy of the oral liquids in the above embodiments and the comparative oral liquids was tested.

[0093] I. Blood lipid-lowering test:

[0094] SPF-grade rats were used, and 120 rats (half male and half female) were randomly divided into 15 groups of 8 rats each: a normal group, a high-fat control group, groups 1-5 (Examples 1-5), and comparative groups 1-8. The normal group was fed only a standard diet daily. The high-fat control group was fed only a high-fat diet daily (high-fat diet: 12% sucrose, 10% egg yolk powder, 15% lard, 2% cholesterol, 0.2% sodium cholate, with the remainder being standard diet). The example and comparative groups were fed a high-fat diet daily, followed by oral administration of 0.5 mL / day of the corresponding oral solution via gavage. After 30 days of continuous feeding, the rats were sacrificed, and blood was collected via the peritoneal vein to determine the serum total cholesterol (TC) and triglyceride (TG) levels. The test results are shown in Table 1 below.

[0095] Table 1. Results of the lipid-lowering test (average value)

[0096]

[0097]

[0098] The results above indicate that the oral liquids of Examples 1 to 5 have excellent lipid-lowering effects. The results of Comparative Examples 1 to 4 show that glycosaminoglycan collagen peptides, cod collagen oligopeptide powder, and bonito elastin peptide-Y all have certain lipid-lowering effects, and their combined use can exert outstanding therapeutic effects. The results of Comparative Examples 5 and 6 show that omitting the enzymatic hydrolysis step with green apples reduces the lipid-lowering efficacy of the resulting product. The results of Comparative Example 7 show that not fermenting birch sap significantly reduces its lipid-lowering efficacy. The results of Comparative Example 8 show that not adding *Lactobacillus cellulose* for fermentation significantly reduces its lipid-lowering efficacy. Therefore, it can be concluded that enzymatic hydrolysis of green apples and fermentation of birch sap with specific bacteria both result in products with good lipid-lowering effects.

[0099] II. Add bone density testing:

[0100] Ninety SPF-grade female weaned SD rats (weight difference range 205±2g) were selected and, after one week of acclimatization, divided into 15 groups of 6 rats each: the normal group was administered 0.5 mL of pure water by gavage per day; the control group was administered calcium carbonate granules by gavage at a dose of 200 mg / kg bw; the example groups were administered the corresponding oral solutions of each example by gavage per day at 0.5 mL; and the comparative groups were administered the corresponding oral solutions of each comparative example by gavage per day at 0.5 mL. Administered once daily for 12 weeks, the final body weight was measured, the rats were sacrificed, and both femurs were removed, dried, and the right femur weight was measured. The calcium content of the right femur was detected using atomic absorption spectrophotometry, and the bone mineral density of the left femur was detected using a fully automated high-resolution X-ray machine. The results are shown in Table 2 below.

[0101] Table 2 includes bone mineral density test results (average).

[0102]

[0103]

[0104] The results above show that the oral liquids of Examples 1 to 5 have a good effect on increasing bone density. The results of Comparative Examples 1 to 4 show that glycosaminoglycan collagen peptides, cod collagen oligopeptide powder, and bonito elastin peptide-Y all have the effect of increasing bone density, and the combined use of the three can exert a significant effect on increasing bone density.

[0105] III. Fatigue Resistance Test:

[0106] Female ICR mice, weighing 20g-22g, were randomly divided into groups of 6 mice each and allowed to acclimatize for 3 days.

[0107] Blank control group: Distilled water, 0.5 mL by gavage daily;

[0108] Example group: 0.5 mL of the oral solution corresponding to each comparative example was administered by gavage daily;

[0109] Comparative control group: 0.5 mL of the oral solution corresponding to each comparative control group was administered by gavage daily;

[0110] After 30 days of continuous gavage, a weighted swimming test was conducted on mice 30 minutes after the last administration. Lead sheets of 3% of the mouse's body weight were attached to the mouse's tail, and the mouse was placed in water at 25°C with a water level of 25cm. Timing was started and ended when the mouse was exhausted. The time of the mouse sinking for the first time and the time of exhaustion were recorded. The longer the time, the better the endurance, that is, the better the anti-fatigue.

[0111] Testing standards: The first sinking standard is when the tip of the mouse's nose first submerges below the water surface; the exhaustion standard is when the mouse remains submerged for 10 seconds without surfacing.

[0112] The test results are shown in Table 3 below.

[0113] Table 3. Fatigue resistance test results (average value)

[0114]

[0115] The results above indicate that the oral liquids of Examples 1 to 5 have excellent anti-fatigue effects. The results of Comparative Examples 1 to 4 show that glycosaminoglycan collagen peptides, cod collagen oligopeptide powder, and bonito elastin peptide-Y all have certain anti-fatigue effects, and their combined use can exert a significant anti-fatigue effect. The results of Comparative Examples 5 and 6 show that omitting the enzymatic hydrolysis step with green apples reduces the anti-fatigue efficacy of the resulting product. The results of Comparative Example 7 show that not fermenting birch sap significantly reduces its anti-fatigue efficacy. The results of Comparative Example 8 show that not adding *Lactobacillus cellulose* for fermentation significantly reduces its anti-fatigue efficacy. Therefore, it can be concluded that enzymatic hydrolysis of green apples and fermentation of birch sap with specific bacteria both result in products with good anti-fatigue effects.

[0116] IV. Immunity Boosting Test

[0117] Female ICR mice, weighing 20g-22g, were randomly divided into groups of 6 mice each and allowed to acclimatize for 3 days.

[0118] Normal control group: Distilled water, 0.5 mL by gavage daily;

[0119] Model control group: Distilled water, 0.5 mL by gavage daily;

[0120] Spleen peptide group: Spleen peptide 1.2g / kg administered by gavage;

[0121] Example group: 0.5 mL of the oral solution corresponding to each comparative example was administered by gavage daily;

[0122] Comparative control group: 0.5 mL of the oral solution corresponding to each comparative control group was administered by gavage daily;

[0123] Normal control group: administered an equal volume of distilled water by gavage;

[0124] Model control group: administered an equal volume of distilled water by gavage;

[0125] Experiment: Except for the normal control group, the other groups were administered cyclophosphamide 40 mg / kg intraperitoneally for two consecutive days after continuous gavage for 3 weeks to suppress the immune system. After continuous gavage for 4 weeks, whole blood was collected by enucleating the mice and dripping the blood into centrifuge tubes containing anticoagulant. The blood was constantly mixed during collection to prevent clotting. 1 ml of anticoagulated whole blood was collected from each mouse, and the total white blood cell count and lymphocyte count were measured using a complete blood cell count analyzer within 24 hours.

[0126] The test results are shown in Table 4 below.

[0127] Table 4. Results of Immunity Boosting Tests (Average Values)

[0128]

[0129]

[0130] The results above indicate that the oral liquids of Examples 1 to 5 have a good effect on improving immunity. The results of Comparative Examples 1 to 4 show that glycosaminoglycan collagen peptides, cod collagen oligopeptide powder, and bonito elastin peptide-Y all have certain immune-enhancing effects, and their combined use can produce outstanding results. The results of Comparative Examples 5 and 6 show that omitting the enzymatic hydrolysis step with green apples reduces the efficacy of the product in improving immunity. The results of Comparative Example 7 show that not fermenting birch sap significantly reduces its immune-enhancing effect. The results of Comparative Example 8 show that not adding *Lactobacillus cellulose* for fermentation significantly reduces its immune-enhancing effect. Therefore, it can be concluded that enzymatic hydrolysis of green apples and fermentation of birch sap with specific bacteria both result in products with good immune-enhancing effects.

Claims

1. A pharmaceutical oral solution of glycosaminoglycans, characterized in that it comprises: The oral liquid is prepared from the following raw materials in parts by mass: 1-5 parts of rich glycosaminoglycan collagen peptide, 1-5 parts of cod collagen oligopeptide powder, 1-5 parts of katsuwonus pelamis elastin peptide-Y, 1-5 parts of sturgeon oligopeptide powder, 1-10 parts of fish collagen tripeptide, 0.1-1 part of vitamin C, 1-10 parts of apple concentrate, 0.1-1 part of citric acid, 0.5-1 part of erythritol, 0.01-0.1 part of food essence, 30-90 parts of birch juice, and 20-40 parts of purified water. The apple concentrate is obtained by sequentially subjecting green apples to bromelain, ficin, and trypsin for step-by-step enzymatic hydrolysis, and then concentrating.

2. The pharmaceutical oral solution of glycosaminoglycans according to claim 1, characterized by the fact that it contains, The rich glycosaminoglycan collagen peptide has a glycosaminoglycan content of 32-42 wt%.

3. The pharmaceutical oral solution of glycosaminoglycans according to claim 1, characterized by the fact that it contains, The total nitrogen content of the cod collagen oligopeptide powder is ≥15 wt%.

4. The pharmaceutical oral solution of glycosaminoglycans according to claim 1, characterized by the fact that it contains, The total content of desmosine and isodesmosine of the katsuwonus pelamis elastin peptide-Y is ≥0.2 wt%.

5. The pharmaceutical oral solution of glycosaminoglycans according to claim 1, characterized by the fact that it contains, The oligopeptide content of the sturgeon oligopeptide powder is ≥75.0 wt%.

6. The pharmaceutical oral solution of glycosaminoglycans according to claim 1, characterized by the fact that it contains, The preparation method of the apple concentrate comprises the following steps: crushing green apples, then mixing the green apples with water in an amount of 4-6 times the mass of the green apples, adjusting the pH to 6.8-7.2, then adding 0.5-1.5 wt% of bromelain based on the mass of the green apples, and subjecting to enzymatic hydrolysis at 50-60°C for 1.5-2 h, high-temperature enzyme inactivation, cooling to room temperature, then adding 0.5-1.5 wt% of ficin based on the mass of the green apples, and subjecting to enzymatic hydrolysis at 60-65°C for 1-1.5 h, high-temperature enzyme inactivation, cooling to room temperature, adjusting the pH to 7.8-8.5, adding 0.5-1 wt% of trypsin based on the mass of the protein, and subjecting to enzymatic hydrolysis at 35-38°C for 1-1.5 h, high-temperature enzyme inactivation, cooling to room temperature, adjusting the pH to 6.8-7.2, filtering with a screen, concentrating to 15-25% of the volume, and obtaining the apple concentrate. The enzyme activity of the bromelain is 100,000 U / g; the enzyme activity of the ficin is 100,000 U / g; the enzyme activity of the trypsin is 100,000 U / g; the high-temperature enzyme inactivation is performed at 90-95°C for 15-20 min; and the screen has a mesh size of 325-500.

7. A pharmaceutical oral solution of glycosaminoglycans according to claim 6, characterized by the fact that it contains, The preparation method of the birch juice comprises the following steps: collecting birch juice, filtering the birch juice with a 200-250 mesh screen to remove impurities and suspended solids, adding 1-5 wt% of glucose, 0.5-1.5 wt% of proteose peptone, and 0.05-0.1 wt% of potassium chloride based on the mass of the birch juice, then adding 0.3-0.8 wt% of Lactobacillus brevis and 0.3-0.8 wt% of Lactobacillus bifidus based on the mass of the birch juice, subjecting to anaerobic fermentation for 20-30 h, high-temperature sterilization, filtering with a 325-500 mesh screen, and obtaining the birch juice. ​ 8. The pharmaceutical oral solution of glycosaminoglycans according to claim 1, characterized by the fact that it contains, ​ 9. A pharmaceutical oral solution of glycosaminoglycans according to claim 8, characterized by the fact that it contains, The bacterial activity of the Lactobacillus brevis is 100 million CFU / g; the bacterial activity of the Lactobacillus fermentum is 100 million CFU / g; the temperature of the high-temperature sterilization is 121-125 DEG C, and the time is 15-20 min.

10. A method for preparing a pharmaceutical oral solution of glycosaminoglycans, for preparing a pharmaceutical oral solution of glycosaminoglycans according to any one of claims 1 to 9, characterized by, The preparation method comprises the following steps: According to the mass fraction, purified water is heated to 60-65 DEG C, then cod collagen oligopeptide powder, fish collagen tripeptide, erythritol, rich glycosaminoglycan collagen peptide, katsuwonus pelamis elastin peptide-Y, gelatin oligopeptide powder, vitamin C and citric acid are added in sequence, stirred and mixed uniformly, apple concentrated juice is added, stirred and mixed uniformly, food essence is added, stirred and mixed uniformly, white birch juice is added for constant volume, filtered by using a 200-250 mesh screen, bottled, sealed, microwave sterilized, and an oral liquid is obtained. The temperature of the microwave sterilization is above 80 DEG C, and the frequency is 2450 MHz.

Images