Composite liver and kidney protective agent as well as preparation method and application thereof

Abstract

The invention discloses a composite liver and kidney protective agent as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The protective agent is prepared from 10%-20% of inosine, 15%-25% of glutamic acid, 10%-15% of cysteine, 15%-20% of glycine, 5%-10% of a coenzyme compound, 10%-20% of small molecule peptide and auxiliary materials. The preparation method comprises the steps of premixing, low-temperature homogenization, spray drying and preparation forming, and uniform distribution of components is ensured through a spray drying technology. The traditional Chinese medicine composition plays a role through a three-stage mechanism of fat removal, repair and regeneration, reduces lipid deposition, scavenges free radicals, repairs hepatocytes and promotes regeneration. The traditional Chinese medicine composition can be used for treating or preventing liver and kidney diseases such as non-alcoholic fatty liver, viral hepatitis and cirrhosis, relieving symptoms such as anorexia, jaundice and bleeding, dispelling the effects of alcohol, protecting the liver and enhancing immunity. The proportion of natural components of the protective agent is more than 80%, the safety is high, multiple targets are synergistic, and the curative effect is superior to that of a single-component medicine.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to a compound liver and kidney protectant with inosine, glutamic acid, cysteine, glycine, coenzyme complex and small molecule peptides as core components, its preparation method and its application in the prevention and treatment of liver and kidney related diseases, hangover relief and liver protection, and enhancement of immune function. Background Technology

[0002] Liver and kidney diseases are prevalent chronic illnesses worldwide, with complex pathogenesis involving multiple pathways such as oxidative stress, lipid metabolism disorders, cell damage, and immune dysfunction. Current treatments largely rely on single-component drugs (such as silymarin and bicyclol) ​​or chemically synthesized agents, which suffer from limitations such as single-target action, limited efficacy, and significant side effects. For example, there is a lack of specific drugs for non-alcoholic fatty liver disease (NAFLD), and viral hepatitis requires long-term antiviral treatment and is prone to drug resistance. Furthermore, the liver and kidney health needs of sub-healthy individuals are not adequately met, and the market lacks safe and effective natural compound preparations. Summary of the Invention

[0003] This invention aims to provide a compound liver and kidney protectant that, through the scientific formulation of multiple natural active ingredients, constructs a multi-target synergistic mechanism to achieve three-stage liver and kidney protection of "fat reduction-repair-regeneration", filling the gap in existing technologies.

[0004] To achieve the above objectives, the present invention provides the following technical solution:

[0005] The compound liver and kidney protectant consists of the following active ingredients by weight percentage:

[0006] Inosine 10%-20%, glutamic acid 15%-25%, cysteine ​​10%-15%, glycine 15%-20%, coenzyme complex 5%-10%, small molecule peptides 10%-20%, and pharmaceutically acceptable excipients as appropriate.

[0007] The active ingredients work synergistically to reduce liver cholesterol and lipid deposition, scavenge free radicals, repair liver cells, promote liver cell regeneration, and nourish the liver.

[0008] Furthermore, the coenzyme complex is selected from one or more combinations of coenzyme Q10, coenzyme A, and nicotinamide adenine dinucleotide; the small molecule peptide is a mixture of short peptides with a molecular weight of less than 1000 Da, derived from animal or plant protein hydrolysates.

[0009] The preparation method of the compound liver and kidney protectant includes the following steps:

[0010] (1) Premixing: Add inosine, glutamic acid, cysteine ​​and glycine to purified water in proportion and stir until completely dissolved to form solution A;

[0011] (2) Addition of active ingredients: Add coenzyme complex and small molecule peptide to solution A in sequence, and homogenize at a low temperature of 2-8℃ for 10-30 minutes to form a uniform mixture B;

[0012] (3) Drying and granulation: Mixture B is made into granules by spray drying technology, with the inlet air temperature controlled at 120-150℃ and the outlet air temperature at 60-80℃, to obtain dried granules C.

[0013] (4) Formulation: Add excipients to granules C, mix evenly, fill into capsules or compress into tablets, and package after sterilization.

[0014] Furthermore, in step (2), the homogenization process is carried out at a pressure of 50-100 MPa and a rotation speed of 1000-3000 rpm.

[0015] Application of compound hepatoprotective agents in the preparation of drugs for the treatment or prevention of the following diseases:

[0016] Liver diseases: including abnormal ALT / AST levels, non-alcoholic fatty liver disease, alcoholic fatty liver disease, simple fatty liver disease, steatohepatitis, hepatitis B, hepatitis C, or cirrhosis;

[0017] Systemic symptoms and complications include loss of appetite, nausea, vomiting, abdominal distension, upper abdominal pain, fatigue, nervousness, jaundice, scleral icterus, or symptoms of increased capillary fragility due to decreased synthesis of clotting factors in the liver, including bleeding from the mouth and nose, gastrointestinal bleeding, and bloody stools.

[0018] Furthermore, the compound hepatoprotective agent achieves its therapeutic effect through the following mechanism:

[0019] Phase 1: Reduce liver cholesterol and lipid deposits, eliminate free radicals, and alleviate liver oxidative stress;

[0020] Phase Two: Repairing damaged liver cells, enhancing liver protein synthesis capacity, and restoring liver function;

[0021] The third stage: nourishing liver tissue, continuously promoting liver cell regeneration, inhibiting tumor cell growth, and reducing the inflammatory response of hepatitis.

[0022] Furthermore, by synergistically clearing acetaldehyde and free radicals produced by alcohol metabolism through small molecule peptides and coenzyme complexes, it protects the gastric mucosa and relieves symptoms of nausea, vomiting, and headache after drinking.

[0023] Furthermore, glycine and small molecule peptides regulate the activity of T lymphocytes and NK cells, thereby inhibiting tumor cell proliferation.

[0024] The beneficial effects of this invention are:

[0025] Multi-target synergy: Covering the entire chain of energy metabolism, anti-oxidation, detoxification, anti-inflammation and regeneration, with significantly better efficacy than single-component drugs.

[0026] High safety profile: Over 80% of the ingredients are natural, and preclinical toxicology tests show an LD50 > 5000 mg / kg (oral in rats) with no mutagenicity.

[0027] It has a wide range of indications: covering the entire course of disease management from fatty liver to cirrhosis, while also meeting the health care needs of sub-healthy people.

[0028] Process controllability: Spray drying technology achieves uniform component distribution, ensuring batch-to-batch stability (RSD<2%). Detailed Implementation

[0029] The present invention will now be described in more detail and in a more complete manner.

[0030] The present invention provides a composite liver and kidney protectant, its preparation method, and its application.

[0031] 1. Core components and synergistic mechanism

[0032] The compound liver and kidney protectant of this invention is composed of the following active ingredients by weight percentage:

[0033] Inosine (10%-20%): As a substrate for liver energy metabolism, it directly participates in the synthesis of adenosine triphosphate (ATP), promotes hepatocyte repair and regeneration, and significantly reduces the volume of enlarged liver.

[0034] Glutamic acid (15%-25%): As a precursor for glutathione (GSH) synthesis, it generates GSH through the transsulfurization pathway, neutralizing free radicals (such as OH and H2O2) and reducing oxidative damage to hepatocytes.

[0035] Cysteine ​​(10%-15%): Provides the rate-limiting amino acid for GSH synthesis, enhances the liver's detoxification ability, and has a protective effect against acetaldehyde produced by alcohol metabolism and drug-induced liver damage.

[0036] Glycine (15%-20%): Regulates the activity of key lipid metabolism enzymes (such as cholesterol 7α-hydroxylase) and reduces lipid deposition in the liver; at the same time, as an essential component of GSH synthesis, it improves liver damage associated with metabolic syndrome.

[0037] Coenzyme complex (5%-10%):

[0038] Coenzyme Q10: Activates the mitochondrial respiratory chain and enhances energy supply to liver cells;

[0039] NAD+: Participates in redox reactions and repairs alcoholic liver damage;

[0040] Coenzyme A: Promotes fatty acid β-oxidation and reduces the progression of fatty liver.

[0041] Small molecule peptides (10%-20%):

[0042] Derived from soybean or fish collagen hydrolysate (molecular weight <1000Da), it penetrates the liver cell membrane to exert its effects directly;

[0043] Activate the AMPK pathway and inhibit lipid synthesis;

[0044] Upregulating Bcl-2 protein expression inhibits hepatocyte apoptosis.

[0045] 2. Three-stage dynamic protection mechanism

[0046] Phase 1 (0-2 weeks): Inosine and coenzyme complex rapidly reduce liver cholesterol and triglyceride levels, while small molecule peptides scavenge free radicals and alleviate oxidative stress;

[0047] Phase 2 (2-4 weeks): Glutamate, cysteine ​​and glycine work together to synthesize GSH, repair damaged liver cell membranes and mitochondria, and increase serum albumin levels;

[0048] Phase 3 (4-8 weeks): Small molecule peptides stimulate hepatocyte DNA synthesis and promote liver lobule regeneration; glycine regulates the immune microenvironment and inhibits the hepatitis-liver fibrosis-hepatocellular carcinoma (HCC) process.

[0049] 3. Scope of Indications

[0050] Liver diseases:

[0051] Metabolic liver diseases: non-alcoholic fatty liver disease, alcoholic fatty liver disease, simple fatty liver disease, steatohepatitis;

[0052] Viral hepatitis: acute / chronic phases of hepatitis B and C;

[0053] End-stage liver disease: compensated / decompensated cirrhosis, liver fibrosis;

[0054] Abnormal liver function: persistently elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

[0055] Systemic symptoms and complications:

[0056] Digestive system symptoms: loss of appetite, nausea, vomiting, abdominal distension, upper abdominal pain;

[0057] Skin system: Jaundice (yellowing of the skin / sclera), spider angiomas, palmar erythema;

[0058] Coagulation disorders: bleeding from the mouth and nose, gastrointestinal bleeding, bloody stools;

[0059] Metabolic syndrome: obesity, type 2 diabetes-related liver damage.

[0060] Sub-health state:

[0061] Fluctuations in liver enzymes caused by prolonged sleep deprivation, overwork, and mental stress;

[0062] Prevention of alcoholic liver damage (hangover relief and liver protection);

[0063] Hepatotoxicity protection after radiotherapy and chemotherapy for tumors. Specific implementation examples:

[0065] 1. Formulation composition (by weight percentage)

[0066]

[0067] 2. Preparation process

[0068] Step 1: Premix

[0069] Inosine, glutamic acid, cysteine, and glycine were added to purified water in a ratio of 1:5 w / v and stirred at 30°C until completely dissolved to form solution A.

[0070] Step 2: Adding active ingredients

[0071] Add the coenzyme complex and small molecule peptide to solution A in sequence, and homogenize it at 80 MPa pressure for 20 minutes (2000 rpm) under low temperature conditions of 2-8℃ to form a homogeneous mixture B.

[0072] Step 3: Spray drying

[0073] Mixture B is pumped into a spray drying tower, and the inlet air temperature is controlled at 135℃ and the outlet air temperature at 70℃ to obtain dried particles C (moisture content <3%).

[0074] Step 4: Formulation

[0075] Add excipients (microcrystalline cellulose: magnesium stearate = 9:1) to granules C, mix well, and fill into No. 0 capsules (each capsule contains 500mg of active ingredient), or compress into round tablets with a diameter of 8mm (each tablet contains 600mg of active ingredient).

[0076] Step 5: Sterilization and Packaging

[0077] Sterilized by cobalt-60 gamma irradiation (dose 25kGy), and packaged into aluminum-plastic blister packs in a clean room with relative humidity <40%, with 30 blister packs per box.

[0078] 3. Quality Standards

[0079] Appearance: White to pale yellow powder or granules, odorless, slightly sweet taste;

[0080] Identification:

[0081] Inosine: Ultraviolet spectrophotometry (λmax = 248 nm);

[0082] Small molecule peptides: Electrophoresis showed a molecular weight distribution of <1000 Da;

[0083] Content determination: The content of each component was determined by high performance liquid chromatography (HPLC), with a deviation of ≤ ±5%;

[0084] Microbial limits: Total bacterial count <1000 CFU / g, molds and yeasts <100 CFU / g, and Escherichia coli must not be detected.

[0085] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A compound liver and kidney protectant, characterized in that, Composed of the following active ingredients by weight percentage: Inosine 10%-20%, glutamic acid 15%-25%, cysteine ​​10%-15%, glycine 15%-20%, coenzyme complex 5%-10%, small molecule peptides 10%-20%, and pharmaceutically acceptable excipients as appropriate. The active ingredients work synergistically to reduce liver cholesterol and lipid deposition, scavenge free radicals, repair liver cells, promote liver cell regeneration, and nourish the liver.

2. The compound liver and kidney protectant according to claim 1, characterized in that: The coenzyme complex is selected from one or more combinations of coenzyme Q10, coenzyme A, and nicotinamide adenine dinucleotide; the small molecule peptide is a mixture of short peptides with a molecular weight of less than 1000 Da, derived from animal or plant protein hydrolysates.

3. The preparation method of the compound liver and kidney protectant according to claim 1, characterized in that, Includes the following steps: (1) Premixing: Add inosine, glutamic acid, cysteine ​​and glycine to purified water in proportion and stir until completely dissolved to form solution A; (2) Addition of active ingredients: Add coenzyme complex and small molecule peptide to solution A in sequence, and homogenize at a low temperature of 2-8℃ for 10-30 minutes to form a uniform mixture B; (3) Drying and granulation: Mixture B is made into granules by spray drying technology, with the inlet air temperature controlled at 120-150℃ and the outlet air temperature at 60-80℃, to obtain dried granules C. (4) Formulation: Add excipients to granules C, mix evenly, fill into capsules or compress into tablets, and package after sterilization.

4. The preparation method according to claim 3, characterized in that: The homogenization process in step (2) is carried out at a pressure of 50-100 MPa and a rotation speed of 1000-3000 rpm.

5. The use of the compound hepatoprotective agent according to claim 1 in the preparation of medicaments for treating or preventing the following diseases: Liver diseases: including abnormal ALT / AST levels, non-alcoholic fatty liver disease, alcoholic fatty liver disease, simple fatty liver disease, steatohepatitis, hepatitis B, hepatitis C, or cirrhosis; Systemic symptoms and complications include loss of appetite, nausea, vomiting, abdominal distension, upper abdominal pain, fatigue, nervousness, jaundice, scleral icterus, or symptoms of increased capillary fragility due to decreased synthesis of clotting factors in the liver, including bleeding from the mouth and nose, gastrointestinal bleeding, and bloody stools.

6. The application according to claim 5, characterized in that: The compound liver and kidney protectant achieves its therapeutic effect through the following mechanism: Phase 1: Reduce liver cholesterol and lipid deposits, eliminate free radicals, and alleviate liver oxidative stress; Phase Two: Repairing damaged liver cells, enhancing liver protein synthesis capacity, and restoring liver function; The third stage: nourishing liver tissue, continuously promoting liver cell regeneration, inhibiting tumor cell growth, and reducing the inflammatory response of hepatitis.

7. The application of the compound liver and kidney protectant according to claim 1 in the preparation of hangover relief and liver protection health products, characterized in that: By working synergistically with small molecule peptides and coenzyme complexes to remove acetaldehyde and free radicals produced by alcohol metabolism, the gastric mucosa is protected and symptoms of nausea, vomiting and headache after drinking are relieved.

8. The application of the compound liver and kidney protectant according to claim 1 in the preparation of drugs that enhance immune function, characterized in that: It inhibits tumor cell proliferation by regulating the activity of T lymphocytes and NK cells through glycine and small molecule peptides.

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