CN115068509A - Pharmaceutical composition containing high-substitution-degree carboxymethyl pachyman and application thereof - Google Patents

Pharmaceutical composition containing high-substitution-degree carboxymethyl pachyman and application thereof Download PDF

Info

Publication number
CN115068509A
CN115068509A CN202110271881.0A CN202110271881A CN115068509A CN 115068509 A CN115068509 A CN 115068509A CN 202110271881 A CN202110271881 A CN 202110271881A CN 115068509 A CN115068509 A CN 115068509A
Authority
CN
China
Prior art keywords
weight
pachymaran
composition
solution
parts
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202110271881.0A
Other languages
Chinese (zh)
Inventor
戴甲木
侯凤飞
戴鑫汶
邹奇
聂蔚
邓声菊
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hunan Busky Pharmaceutical Co ltd
Original Assignee
Hunan Busky Pharmaceutical Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hunan Busky Pharmaceutical Co ltd filed Critical Hunan Busky Pharmaceutical Co ltd
Priority to CN202110271881.0A priority Critical patent/CN115068509A/en
Publication of CN115068509A publication Critical patent/CN115068509A/en
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/745—Bifidobacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/10—Laxatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/10—Antioedematous agents; Diuretics
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0003—General processes for their isolation or fractionation, e.g. purification or extraction from biomass
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
    • C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Hematology (AREA)
  • Immunology (AREA)
  • Biochemistry (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Obesity (AREA)
  • Materials Engineering (AREA)
  • Polymers & Plastics (AREA)
  • Toxicology (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Anesthesiology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Nutrition Science (AREA)
  • Virology (AREA)
  • Neurosurgery (AREA)
  • Sustainable Development (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention relates to a pharmaceutical composition containing high-substitution-degree carboxymethyl pachyman, which is characterized by comprising the following components in parts by weight: 0.5-3 parts of tuckahoe, 5-12 parts of prebiotics and 0.005-0.03 part of probiotics. The composition has the effects of strengthening the spleen and stomach, helping digestion, enhancing immunity, repairing intestinal tracts and functions, bidirectionally regulating diarrhea and constipation, resisting inflammation, detoxifying and the like.

Description

Pharmaceutical composition containing high-substitution-degree carboxymethyl pachyman and application thereof
Technical Field
The invention relates to the field of biological medicine, in particular to a pharmaceutical composition containing high-substitution-degree carboxymethyl pachyman, a preparation method and application thereof.
Background
Poria is fungus belonging to Poria of Polyporales, has effects of promoting diuresis, eliminating dampness, invigorating spleen, calming heart and tranquilizing mind, and can be used for preventing and treating edema, oliguria, phlegm and fluid retention, dizziness and palpitation, spleen deficiency, anorexia, loose stool, diarrhea, uneasiness, palpitation, insomnia, etc. The carboxymethyl pachyman extracted and prepared from tuckahoe has excellent pharmacological action:1) depends on the immune system of the host, enhances the immunity of the organism (specificity and non-specificity), inhibits and kills the tumor cells. By activating complement, various lymphocyte active factors are induced, the activity of macrophages, NK cells, T lymphocytes and B lymphocytes is enhanced, and the anti-tumor and anti-virus effects are exerted through multi-way synergy; 2) inhibit the synthesis of DNA and RNA of tumor cells, and directly kill and kill the tumor cells; 3) increasing Sialic Acid (SA) content on tumor cell membrane, inhibiting PI conversion, and reducing arachidonic acid (C) 20 ) The multiple pathway inhibits division and proliferation of tumor cells; 4) enhancing liver SOD activity, scavenging oxygen free radicals, decomposing carcinogen, and preventing DNA variation of normal cells.
Disclosure of Invention
The invention aims to provide a pharmaceutical composition containing carboxymethyl pachyman with high degree of substitution, which comprises the following components in parts by weight: 0.5-3 parts of tuckahoe, 5-12 parts of prebiotics and 0.005-0.03 part of probiotics.
In the preferable technical scheme of the invention, the content of the tuckahoe in the composition is 1 to 2.5 parts, and preferably 1.5 to 2 parts.
In a preferred technical scheme of the invention, the poria cocos in the composition is any one of pachymaran alkalization extract, pachymaran and carboxymethyl pachymaran (CMP) with high degree of substitution.
In the preferred technical scheme of the invention, the preparation method of the high-substitution-degree carboxymethyl pachyman comprises the following steps: 1) adding pachymaran into water or water-alcohol mixed solution, stirring, adding alkaline solution with a mass of 1-8% of pachymaran, and stirring to completely dissolve to obtain pachymaran alkalized solution; 2) and (2) after fully reacting 1.0-10mol/L chloroacetic acid with proper excess 2.0-10mol/L alkaline solution, adding the obtained product into the pachyman alkalization solution obtained in the step 1), and performing substitution reaction, separation and purification to obtain the pachyman alkalization solution, wherein the proper excess is that the actual dosage of alkaline substances in the alkaline solution is 0.5-40% more than the theoretical dosage required by the neutralization reaction between the alkaline substances and chloroacetic acid.
In a preferable technical scheme of the invention, the pachyman obtained in step 1) is selected from pachyman alkaline extract obtained by an alkaline extraction method or pachyman crude product obtained by an alkaline extraction and acid precipitation method.
In the preferred technical scheme of the invention, the preparation method of the pachyman alkalization extracting solution comprises the following steps of adding the tuckahoe powder into an alkaline solution with the concentration of 1.0-4.0mol/L for alkalization extraction, carrying out centrifugal separation, and taking the supernatant to obtain the pachyman alkalization extracting solution.
In the preferred technical scheme of the invention, the preparation method of the pachymaran comprises the following steps of stirring and extracting tuckahoe powder by using an alkaline solution with the concentration of 1.0-4.0mol/L, performing centrifugal separation, and taking supernatant; adding acid into the supernatant, centrifuging the obtained acid precipitate, and washing with water to obtain pachyman, wherein the acid is selected from one of acetic acid, hydrochloric acid, sulfuric acid, and nitric acid.
In the preferable technical scheme of the invention, the concentration of the alkaline solution is 2.0-3.0 mol/L.
In a preferred technical scheme of the invention, the water-alcohol mixed solution is a solution prepared by adding water into an alcohol solvent, wherein the alcohol solvent is any one or a combination of methanol, ethanol, propylene glycol, ethyl acetate, acetone, dimethyl sulfoxide, diethyl ether, isopropanol and dimethylformamide.
In the preferable technical scheme of the invention, the alkaline solution added in the step 1) is 2-6% of the weight of the pachymaran, and the alkaline solution added in the step 1) is preferably 3-5% of the weight of the pachymaran.
In a preferred technical scheme of the invention, the alkaline solution is prepared by dissolving an alkaline substance in water, wherein the alkaline substance is any one or combination of sodium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate.
In a preferred embodiment of the present invention, the alkaline substance is selected from any one of sodium hydroxide or potassium hydroxide, or a combination thereof.
In a preferred technical scheme of the invention, the concentration of the chloroacetic acid solution is 2.0-9.0mol/L, preferably 3.0-8.0mol/L, more preferably 4.0-7.0mol/L, and further preferably 4.5-6.0 mol/L.
In a preferable technical scheme of the invention, the concentration of the alkaline solution in the step 2) is 3.0-9.0mol/L, preferably 4.0-8.0mol/L, more preferably 5.0-7.0mol/L, and still more preferably 5.5-6.5 mol/L.
In a preferred embodiment of the present invention, the proper excess means that the actual amount of the alkaline substance in the alkaline solution is 5-30%, preferably 10-25%, and more preferably 15-20% more than the theoretical amount required for the neutralization reaction with chloroacetic acid.
In the preferable technical scheme of the invention, the reaction solution in the step 2) is subjected to substitution reaction for 1-5h at the temperature of 30-100 ℃.
In the preferable technical scheme of the invention, the reaction time in the step 2) is 2-4h, preferably 2.5-3.5 h.
In the preferable technical scheme of the invention, the reaction temperature in the step 2) is 40-90 ℃, preferably 50-85 ℃, more preferably 60-82 ℃ and further preferably 75-80 ℃.
In a preferred technical scheme of the invention, the separation comprises the following steps of adding 1.0-10mol/L acid solution into the reaction product liquid obtained in the step 2), adjusting the pH value to 5.0-7.0, adding 3-5 times of volume of alcohol solvent to precipitate a CMP crude product, wherein the alcohol solvent is selected from any one or combination of methanol, ethanol, propylene glycol, ethyl acetate, isopropanol, diethyl ether and acetone.
In a preferred technical scheme of the invention, the acidic solution is prepared by dissolving an acidic substance in water, wherein the acidic substance is selected from any one or combination of acetic acid, hydrochloric acid, sulfuric acid or nitric acid.
In the preferred technical scheme of the invention, the purification comprises the following steps of adding water into CMP to be purified to prepare 1.0-6.0% aqueous solution, adding 1.0-10mol/L alkaline solution to adjust the pH value to 9.0-12.0, and stirring until the CMP is completely dissolved; adding 30% of H 2 O 2 The solution with the dosage of 0.1 per mill to 2.0 per mill of the total volume of the solution is subjected to decolorization reaction; adding 1.0-10mol/L acid solution to adjust pH to 5.0-7.0, ultrafiltering to remove molecular weight less than 0.7 × 10 4 Dalton CMP and other small molecule impurities.
In a preferred embodiment of the present invention, the concentration of the aqueous CMP solution to be purified is 2.0 to 5.0%, preferably 3 to 4%.
In a preferred embodiment of the present invention, the concentration of the alkaline solution used in the purification step is 2.0 to 9.0mol/L, preferably 3.0 to 8.0mol/L, more preferably 4.0 to 7.0mol/L, and still more preferably 5.0 to 6.0 mol/L.
In the preferable technical scheme of the invention, the content of the 30% H is 2 O 2 The dosage of the solution is 0.5-1.0 ‰ of the total volume of the solution.
In the preferred technical scheme of the invention, the decolorizing reaction temperature is 10-70 ℃, preferably 15-60 ℃, and more preferably 20-50 ℃.
In a preferred technical scheme of the invention, the time of the decolorization reaction is 2-48h, preferably 5-40h, more preferably 10-30h, and still more preferably 15-25 h.
In a preferred embodiment of the present invention, the concentration of the acidic solution is 1.0 to 9.0mol/L, preferably 2.0 to 8.0mol/L, more preferably 3.0 to 7.0mol/L, and preferably 4.0 to 6.0 mol/L.
In the preferred technical scheme of the invention, the ultrafiltration medium is a DH-UF hollow fiber ultrafilter.
In a preferred technical scheme of the invention, the separation and purification is repeated separation and purification.
In a preferred embodiment of the present invention, the substitution degree of CMP is not less than 1.05, preferably not less than 1.10, and more preferably not less than 1.2.
In a preferred embodiment of the present invention, the molecular weight of the CMP is 0.7X 10 4 -1.0×10 6 Dalton, preferably 3.0X 10 4 -8×10 5 Dalton, more preferably 6.0X 10 4 -5.0×10 5 Dalton, preferably also 8.0X 10 4 -3.0×10 5 And D, dalton.
In a preferred embodiment of the present invention, the polymerization degree of CMP is 32< n <4545, preferably 136< n <3636, more preferably 272< n <2272, and further preferably 363< n < 1363.
In the preferable technical scheme of the invention, the prebiotics in the composition are 6-10 parts by weight, and 8-9 parts by weight is preferable.
In a preferred embodiment of the present invention, the prebiotics are selected from any one of isomaltose oligosaccharide, sorbose, glucose, rhamnose, xylose, arabinose, fucose, gulose, mannose, lyxose, stachyose, fructo-oligosaccharide, galacto-oligosaccharide, hemicellulose, and lactulose oligosaccharide, or a combination thereof.
In a preferred technical scheme of the invention, the weight part of the probiotics in the composition is 0.01-0.025 parts, and preferably 0.015-0.02 parts.
In a preferred technical scheme of the invention, the probiotics are selected from any one of bifidobacteria, bacillus subtilis, rhamnosus and bifidobacterium lactis or a combination thereof.
In a preferred technical scheme of the invention, the composition comprises the following components, by weight, 2-4 parts of isomaltose hypgather, 2-4 parts of fructo-oligosaccharide, 1-3 parts of glucose, 1-3 parts of poria cocos, 0.5-1 part of stachyose, 0.006-0.008 part of rhamnosus bacillus and 0.006-0.008 part of bifidobacterium lactis.
In a preferable technical scheme of the invention, the composition contains the following components of 2 parts by weight of isomaltooligosaccharide, 2 parts by weight of fructo-oligosaccharide, 1 part by weight of glucose, 1 part by weight of tuckahoe, 0.5 part by weight of stachyose, 0.006 part by weight of rhamnose bacillus and 0.006 part by weight of bifidobacterium lactis.
In a preferred embodiment of the present invention, the composition further comprises a pharmaceutically acceptable carrier in a desired amount.
In a preferred embodiment of the present invention, the pharmaceutically acceptable carrier is selected from any one of or a combination of fillers (also called diluents), lubricants (also called glidants or antiadherents), dispersants, wetting agents, binders, regulators, solubilizers (also called stabilizers), antioxidants, emulsifiers, flavors, and flavoring agents.
In a preferred technical scheme of the invention, the binding agent is selected from any one or combination of syrup, Arabic gum, gelatin, sorbitol, tragacanth, cellulose, microcrystalline cellulose, sodium carboxymethyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, gelatin slurry, syrup, starch, sodium carboxymethyl starch, sodium starch glycolate, pregelatinized starch, modified starch, hydroxypropyl starch, corn starch, starch slurry and polyvinylpyrrolidone.
In a preferred technical scheme of the invention, the filler is selected from any one of lactose, powdered sugar, dextrin, starch or derivatives thereof, cellulose, microcrystalline cellulose, sodium carboxymethyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, calcium sulfate, calcium phosphate, calcium hydrogen phosphate, precipitated calcium carbonate, sorbitol, glycine, sodium carboxymethyl starch, sodium starch glycolate, pregelatinized starch, modified starch, hydroxypropyl starch and corn starch or a combination thereof.
In a preferred technical scheme of the invention, the lubricant is selected from any one of or a combination of superfine silica powder, magnesium stearate, talcum powder, aluminum hydroxide, boric acid, hydrogenated vegetable oil and polyethylene glycol.
In a preferred technical scheme of the invention, the disintegrating agent is selected from any one of starch, sodium carboxymethyl starch, sodium starch glycolate, pregelatinized starch, modified starch, hydroxypropyl starch, corn starch, polyvinylpyrrolidone, cross-linked polyvinylpyrrolidone and microcrystalline cellulose or a combination thereof.
In a preferred embodiment of the present invention, the wetting agent is selected from any one of sodium lauryl sulfate, water, alcohol, or a combination thereof.
In a preferred technical scheme of the invention, the emulsifier is selected from any one of polysorbate-80, sorbitan fatty acid, pluronic F-68, lecithin and soybean lecithin or a combination thereof.
In a preferred embodiment of the present invention, the acid-base regulator is selected from any one of inorganic acids and organic acids or a combination thereof, preferably selected from any one of citric acid, sodium citrate, malic acid, sodium malate, hydrochloric acid, acetic acid, sodium acetate, phosphoric acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, carbonic acid, sodium carbonate, sulfonic acid, sodium sulfonate, glutamic acid, tartaric acid, sodium tartrate, lactic acid, sodium lactate, fumaric acid, sodium fumarate, itaconic acid, ascorbic acid, sodium ascorbate, nicotinic acid, sodium nicotinate, fumaric acid, α -ketoglutaric acid, tartaric acid, sodium malate, acetic acid, oxalic acid, succinic acid, carbon dioxide, citric acid, and sodium citrate, or a combination thereof.
In the preferable technical scheme of the invention, the concentration of the pH regulator is 0.5-8mol/L, preferably 0.8-6mol/L, more preferably 1-5mol/L, and further preferably 2-4 mol/L.
In a preferred embodiment of the present invention, the stabilizer (solubilizer) is selected from any one of glycerol, tween-80, or a combination thereof.
In a preferred technical scheme of the invention, the antioxidant is selected from any one of potassium sorbate, sodium sulfite, sodium bisulfite, sodium metabisulfite and dibutylbenzoic acid or a combination thereof.
In a preferred technical scheme of the invention, the aromatizer is selected from any one of spice, edible spice and flavoring essence or the combination thereof.
The compositions of the present invention may be in various dosage forms well known in the art and may be prepared using formulation techniques conventional in the art.
In a preferred technical scheme of the invention, the composition is an oral preparation.
In a preferred technical scheme of the invention, the oral preparation is selected from any one of oral liquid (liquid preparation), syrup, suspension, tablets, capsules, granules, pills, powder, dripping pills, mixture, distillate, effervescent, paste, emulsion and tea.
In addition, the active ingredient and the pharmaceutically acceptable sustained-release carrier can be mixed according to the preparation requirements, and then prepared into pellets, such as sustained-release pellets or controlled-release pellets, according to the preparation method of the sustained-release preparation well known in the art, such as adding a retardant coating or microencapsulating the active ingredient; the sustained and controlled release carrier comprises but is not limited to an oil-fat doping agent, a hydrophilic colloid, a coating retarder and the like, wherein the oil-fat doping agent is selected from any one or the combination of glyceryl monostearate, hydrogenated castor oil, mineral oil, polysiloxane and dimethyl siloxane; the hydrophilic colloid is selected from any one or combination of sodium carboxymethylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, PVP, acacia, tragacanth and carbopol; the coating retarder is selected from any one of Ethyl Cellulose (EC), hydroxypropyl methyl cellulose (HMPC), polyvinylpyrrolidone (PVP), Cellulose Acetate Phthalate (CAP), acrylic resin or their combination.
The invention also aims to provide a preparation method of a pharmaceutical composition containing high-substitution carboxymethyl pachyman, wherein the composition contains 0.5-3 parts of tuckahoe, 5-12 parts of prebiotics and 0.005-0.03 part of probiotics by weight, and comprises the following steps:
s1, the Poria is any one of pachymaran alkalized extractive solution, pachymaran, and high-substitution degree carboxymethyl pachymaran (CMP);
s2, drying any one of pachymaran alkalization extract, pachymaran and high-substitution-degree carboxymethyl pachymaran (CMP), pulverizing, sieving, adding required amount of prebiotics, probiotics and pharmaceutically acceptable carrier, mixing, and drying.
In the preferable technical scheme of the invention, the content of the tuckahoe in the composition is 1 to 2.5 parts, and preferably 1.5 to 2 parts.
In a preferred technical scheme of the invention, the poria cocos in the composition is any one of pachymaran alkalization extract, pachymaran and carboxymethyl pachymaran (CMP) with high degree of substitution.
In the preferred technical scheme of the invention, the preparation method of the high-substitution-degree carboxymethyl pachyman comprises the following steps: 1) adding pachymaran into water or water-alcohol mixed solution, stirring, adding alkaline solution with a mass of 1-8% of pachymaran, and stirring to completely dissolve to obtain pachymaran alkalized solution; 2) and (2) after fully reacting 1.0-10mol/L chloroacetic acid with proper excess 2.0-10mol/L alkaline solution, adding the obtained product into the pachyman alkalization solution obtained in the step 1), and performing substitution reaction, separation and purification to obtain the pachyman alkalization solution, wherein the proper excess is that the actual dosage of alkaline substances in the alkaline solution is 0.5-40% more than the theoretical dosage required by the neutralization reaction between the alkaline substances and chloroacetic acid.
In a preferable technical scheme of the invention, the pachyman obtained in step 1) is selected from pachyman alkaline extract obtained by an alkaline extraction method or pachyman crude product obtained by an alkaline extraction and acid precipitation method.
In the preferred technical scheme of the invention, the preparation method of the pachyman alkalization extracting solution comprises the following steps of adding the tuckahoe powder into an alkaline solution with the concentration of 1.0-4.0mol/L for alkalization extraction, carrying out centrifugal separation, and taking the supernatant to obtain the pachyman alkalization extracting solution.
In the preferred technical scheme of the invention, the preparation method of the pachymaran comprises the following steps of stirring and extracting tuckahoe powder by using an alkaline solution with the concentration of 1.0-4.0mol/L, performing centrifugal separation, and taking supernatant; adding acid into the supernatant, centrifuging the obtained acid precipitate, and washing with water to obtain pachyman, wherein the acid is selected from one of acetic acid, hydrochloric acid, sulfuric acid, and nitric acid.
In the preferable technical scheme of the invention, the concentration of the alkaline solution is 2.0-3.0 mol/L.
In a preferred technical scheme of the invention, the water-alcohol mixed solution is a solution prepared by adding water into an alcohol solvent, wherein the alcohol solvent is any one or a combination of methanol, ethanol, propylene glycol, ethyl acetate, acetone, dimethyl sulfoxide, diethyl ether, isopropanol and dimethylformamide.
In the preferable technical scheme of the invention, the alkaline solution added in the step 1) is 2-6% of the weight of the pachymaran, and the alkaline solution added in the step 1) is preferably 3-5% of the weight of the pachymaran.
In a preferred technical scheme of the invention, the alkaline solution is prepared by dissolving an alkaline substance in water, wherein the alkaline substance is any one or combination of sodium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate.
In a preferred embodiment of the present invention, the alkaline substance is selected from any one of sodium hydroxide or potassium hydroxide, or a combination thereof.
In a preferred technical scheme of the invention, the concentration of the chloroacetic acid solution is 2.0-9.0mol/L, preferably 3.0-8.0mol/L, more preferably 4.0-7.0mol/L, and further preferably 4.5-6.0 mol/L.
In a preferable technical scheme of the invention, the concentration of the alkaline solution in the step 2) is 3.0-9.0mol/L, preferably 4.0-8.0mol/L, more preferably 5.0-7.0mol/L, and still more preferably 5.5-6.5 mol/L.
In a preferred embodiment of the present invention, the proper excess means that the actual amount of the alkaline substance in the alkaline solution is 5-30%, preferably 10-25%, and more preferably 15-20% more than the theoretical amount required for the neutralization reaction with chloroacetic acid.
In the preferable technical scheme of the invention, the reaction solution in the step 2) is subjected to substitution reaction for 1-5h at the temperature of 30-100 ℃.
In the preferable technical scheme of the invention, the reaction time in the step 2) is 2-4h, preferably 2.5-3.5 h.
In the preferable technical scheme of the invention, the reaction temperature in the step 2) is 40-90 ℃, preferably 50-85 ℃, more preferably 60-82 ℃ and further preferably 75-80 ℃.
In a preferred technical scheme of the invention, the separation comprises the following steps of adding 1.0-10mol/L acid solution into the reaction product liquid obtained in the step 2), adjusting the pH value to 5.0-7.0, adding 3-5 times of volume of alcohol solvent to precipitate a CMP crude product, wherein the alcohol solvent is selected from any one or combination of methanol, ethanol, propylene glycol, ethyl acetate, isopropanol, diethyl ether and acetone.
In a preferred technical scheme of the invention, the acidic solution is prepared by dissolving an acidic substance in water, wherein the acidic substance is selected from any one or combination of acetic acid, hydrochloric acid, sulfuric acid or nitric acid.
In the preferred technical scheme of the invention, the purification comprises the following steps of adding water into CMP to be purified to prepare 1.0-6.0% aqueous solution, adding 1.0-10mol/L alkaline solution to adjust the pH value to 9.0-12.0, and stirring until the CMP is completely dissolved; adding 30% of H 2 O 2 The solution with the dosage of 0.1 per mill to 2.0 per mill of the total volume of the solution is subjected to decolorization reaction; adding 1.0-10mol/L acid solution to adjust pH to 5.0-7.0, ultrafiltering to remove molecular weight less than 0.7 × 10 4 Dalton CMP and other small molecule impurities.
In a preferred embodiment of the present invention, the concentration of the aqueous CMP solution to be purified is 2.0 to 5.0%, preferably 3 to 4%.
In a preferred embodiment of the present invention, the concentration of the alkaline solution used in the purification step is 2.0 to 9.0mol/L, preferably 3.0 to 8.0mol/L, more preferably 4.0 to 7.0mol/L, and still more preferably 5.0 to 6.0 mol/L.
In the preferable technical scheme of the invention, the 30% H 2 O 2 The dosage of the solution is 0.5-1.0 ‰ of the total volume of the solution.
In the preferred technical scheme of the invention, the decolorizing reaction temperature is 10-70 ℃, preferably 15-60 ℃, and more preferably 20-50 ℃.
In a preferred technical scheme of the invention, the time of the decolorization reaction is 2-48h, preferably 5-40h, more preferably 10-30h, and still more preferably 15-25 h.
In a preferred embodiment of the present invention, the concentration of the acidic solution is 1.0-9.0mol/L, preferably 2.0-8.0mol/L, more preferably 3.0-7.0mol/L, and preferably 4.0-6.0 mol/L.
In the preferred technical scheme of the invention, the ultrafiltration medium is a DH-UF hollow fiber ultrafilter.
In a preferred technical scheme of the invention, the separation and purification is repeated separation and purification.
In a preferred embodiment of the present invention, the substitution degree of CMP is not less than 1.05, preferably not less than 1.10, and more preferably not less than 1.2.
In a preferred embodiment of the present invention, the molecular weight of the CMP is 0.7X 10 4 -1.0×10 6 Dalton, preferably 3.0X 10 4 -8×10 5 Dalton, more preferably 6.0X 10 4 -5.0×10 5 Dalton, preferably also 8.0X 10 4 -3.0×10 5 And D, dalton.
In a preferred embodiment of the present invention, the CMP polymerization degree is 32< n <4545, preferably 136< n <3636, more preferably 272< n <2272, and further preferably 363< n < 1363.
In the preferred technical scheme of the invention, the screen in the S3 is 20-60 meshes, preferably 30-40 meshes.
The invention also aims to provide application of the pharmaceutical composition containing the carboxymethyl pachyman with high degree of substitution in preparing a product for improving gastrointestinal function.
In a preferred technical scheme of the invention, the gastrointestinal function improvement is any one of immunity enhancement, tumor resistance, virus resistance, radiation resistance, liver protection, bacteria resistance, diuresis, sleep improvement, blood sugar reduction, blood fat reduction, aging resistance, fatigue resistance, constipation prevention, gastrointestinal inflammation prevention and dyspepsia prevention.
In a preferred embodiment of the present invention, the constipation is selected from the group consisting of neoplastic constipation, functional constipation, drug-induced constipation, organic constipation, acute constipation, chronic constipation, alternate constipation and diarrhea.
In a preferred embodiment of the present invention, the dosage of the composition is related to the age, sex, health status, current treatment status, concomitant medication and the like of the patient, and the recommended dosage is 5-10 g/time and 2-3 times/day.
In a preferred embodiment of the present invention, when the composition is used for preventing constipation, the user can take the composition of the present invention 1 to 3 days before taking a product which causes constipation symptoms, and the recommended dose is 5 to 10 g/time and 1 to 2 times/day.
It is another object of the present invention to provide a pharmaceutical composition comprising highly substituted carboxymethyl pachyman, said composition comprising the composition of the present invention in combination with any one of a fiber supplement, a drug, a probiotic, or a combination thereof.
In a preferred technical scheme of the invention, the microecological preparation is selected from any one of probiotics and prebiotics or a combination thereof.
For clarity of presentation, the following terms are defined as follows:
1. the "B/E value" in the present invention is the ratio of the number of bifidobacteria to the number of enterobacteria in vivo. The B/E value is used as an index for evaluating the intestinal microorganism colonization resistance, and the influence of the composition and the combination mode thereof on microorganisms such as bifidobacteria, enterobacteria, enterococci, saccharomycetes and the like of a constipation patient is qualitatively and quantitatively detected to verify the beneficial effect of the composition for regulating intestines and stomach.
Intestinal microbial Colonization Resistance (CR) was proposed in 1971 by professor Van derwaaij of the Netherlands microbiologist and refers to the ability of intestinal endogenous obligate anaerobes to suppress the number of potentially pathogenic flora of the major aerobic species in the digestive tract. Research shows that the B/E value is less than 1, which indicates that the intestinal colonization resistance is damaged (Wuzhongwen, a new index of intestinal microbial colonization resistance-B/E value, Zhejiang preventive medicine, 2000, 12: 4-5). The lower the B/E value is, the weaker the intestinal tract colonization resistance of a patient is, the lower the pathogenic bacterium invasion resistance is, and the gastrointestinal function problem is more easily caused.
The invention adopts a plate counting method to measure the quantity of bifidobacteria and the quantity of enterobacteria in the excrement of a patient, thereby calculating the quantity ratio (B/E value) of the bifidobacteria and the enterobacteria.
Unless otherwise indicated, when the present invention relates to percentages between liquids, said percentages are volume/volume percentages; the invention relates to the percentage between liquid and solid, said percentage being volume/weight percentage; the invention relates to the percentages between solid and liquid, said percentages being weight/volume percentages; the balance being weight/weight percent.
Compared with the prior art, the invention has the following beneficial technical effects:
1. the composition of the invention scientifically screens the components and the proportion of the tuckahoe, the probiotics and the prebiotics, fully exerts the synergistic interaction of various components, bidirectionally regulates the balance of intestinal flora, enhances the capability of the intestinal mucosa to resist pathogenic bacteria and toxins, promotes the intestinal peristalsis, and effectively prevents and treats gastrointestinal diseases; the dietary fiber is supplemented, the absorption of nutrient substances by the stomach and intestine is promoted, the stomach and intestine function is obviously improved, and the immunity of the organism is improved.
2. The preparation method of the composition has the advantages of simple and convenient operation and obvious cost benefit, and is suitable for industrial mass production.
Detailed Description
The present invention is described below with reference to examples. The invention is not limited to the examples.
Example 1 preparation of a composition for improving gastrointestinal function
The composition is prepared from the following components in parts by weight:
Figure BDA0002974495430000151
Figure BDA0002974495430000161
the preparation method of the composition comprises the following steps:
s1, coarsely crushing 75kg of poria cocos by using a traditional Chinese medicine crusher to 10-200 meshes to obtain poria cocos coarse powder, and weighing the poria cocos coarse powder with required amount;
1) putting Poria coarse powder into soaking tank, pumping 400L water, stirring, and soaking for 12 hr;
2) slowly pumping 400L of 2.25mol/L sodium hydroxide solution into a soaking tank, stirring for reaction for 1 hour, and filtering to obtain filtrate;
3) adding 300L of chloroacetic acid solution with the concentration of 5.3mol/L into a neutralization tank, slowly adding 300L of sodium hydroxide solution with the concentration of 6.25mol/L, stirring until the reaction is fully carried out, and cooling to room temperature;
4) pumping the reaction solution obtained in the step 3) into the filtrate obtained in the step 2), fully and uniformly mixing, slowly heating to 75 ℃, and reacting for 2.5 hours at constant temperature;
5) adjusting pH value of the reaction solution obtained in the step 4) to 5.0-7.0 by using 6mol/L hydrochloric acid solution, adding 95% ethanol with volume being 3 times of that of the reaction solution, uniformly stirring, filtering, washing, and taking CMP alcohol precipitate;
6) drying the CMP alcohol precipitate at 60 deg.C for 4 hr, and drying at 105 deg.C for 2 hr to obtain CMP crude product 37.5 kg;
7) dispersing 7.5kg of the CMP crude product in 250L of double distilled water, and adding 6mol/L of sodium hydroxide solution to adjust the pH value to 10.0-13.0; 1.25L of 30% H are added 2 O 2 Carrying out a decoloring reaction on the solution at 15 ℃ for 36 hours to remove colored impurities; adding 6mol/L hydrochloric acid solution to adjust pH value to 6.0, centrifuging at 3000 r/min for 30min, collecting filtrate, filtering the filtrate with DH-UF hollow fiber ultrafilter to remove CMP with molecular weight below 0.7 × 104 and trace amount of sodium chloride, sodium chloroacetate and sodium glycolate, adding 95% ethanol with 3 times of filtrate volume, precipitating with ethanol, filtering or centrifuging, drying the CMP ethanol precipitate at 60 deg.C for 4h, drying at 105 deg.C for 2h, and pulverizing to obtain 6.0kg of pure CMP product with carboxymethyl substitution of 1.0:
s3, grinding the CMP pure product, sieving with a 60-mesh sieve, adding required amounts of isomaltose hypgather, fructo-oligosaccharide, edible glucose, stachyose, lactobacillus rhamnosus and bifidobacterium lactis, uniformly mixing, and drying to obtain the product.
Example 2
The composition is prepared from the following components in parts by weight:
Figure BDA0002974495430000171
the preparation method of the composition comprises the following steps:
s1, coarsely crushing 75kg of poria cocos by using a traditional Chinese medicine crusher to obtain coarse poria cocos powder; the traditional Chinese medicine crusher is used for crushing the traditional Chinese medicine into 10-200 meshes;
s2 preparation of Poria extract
1) Pumping 400L of water into the coarse powder of Poria cocos, uniformly stirring, and soaking for 14 h;
2) slowly pumping 400L of 3mol/L sodium hydroxide solution into a soaking tank, stirring for reaction for 1 hour, and filtering to obtain filtrate;
3) adding 300L of chloroacetic acid solution with the concentration of 5.5mol/L into a neutralization tank, slowly adding 300L of sodium hydroxide solution with the concentration of 6.5mol/L, stirring until the reaction is fully carried out, and cooling to room temperature;
4) pumping the reaction solution obtained in the step 3) into the filtrate obtained in the step 2), fully and uniformly mixing, slowly heating to 78 ℃, and reacting for 2 hours at constant temperature;
5) adjusting the pH value of the reaction solution obtained in the step 4) to 6.0 by using 6mol/L hydrochloric acid solution, adding 95% ethanol with the volume being 3 times that of the reaction solution, uniformly stirring, filtering, washing, and taking a CMP alcohol precipitate;
6) the CMP alcohol precipitate was dried at 60 ℃ for 4 hours and then at 105 ℃ for 2 hours to obtain 37.8kg of a CMP crude product.
7) Dispersing 7.5kg of the CMP crude product in 250L of double distilled water, and adding 6.5mol/L of sodium hydroxide solution to adjust the pH value to 10.0-13.0; adding 1.5L of 30% H2O2 solution, decolorizing at 25 deg.C for 20 hr, and removing colored impurities; adding 6.5mol/L hydrochloric acid solution to adjust pH to 6.0, centrifuging at 3000 r/L for 30min, filtering with DH-UF hollow fiber ultrafilter to remove the filtrate with molecular weight of 0.7 × 10 4 Adding 95% ethanol 3.2 times the volume of the filtrate into the filtrate, performing alcohol precipitation, filtering or centrifuging, collecting CMP alcohol precipitate at 60 deg.CDrying for 4h and at 105 deg.C for 2h, pulverizing to obtain 6.0kg pure CMP product with carboxymethyl substitution degree of 1.05 and relative molecular weight of 0.7 × 10 4 -1.0×10 6 And D, dalton.
S3, crushing the pure CMP product, and sieving the crushed pure CMP product with a 60-mesh sieve. Adding isomaltooligosaccharide, fructo-oligosaccharide, edible glucose, stachyose, Lactobacillus rhamnosus, and Bifidobacterium lactis, mixing, and drying;
and S4, subpackaging, and 5g in each bag.
Comparative example 1
The composition is prepared from the following components in parts by weight:
Figure BDA0002974495430000191
the preparation method of the composition comprises the following steps:
s1, coarsely crushing 60kg of poria cocos by using a traditional Chinese medicine crusher to obtain coarse poria cocos powder, and weighing the coarse poria cocos powder according to a formula ratio; the traditional Chinese medicine crusher is used for crushing the traditional Chinese medicine into 10-200 meshes;
s2, extracting and concentrating: firstly, adding 10 times of purified water into the coarse powder of the tuckahoe, soaking for 30 minutes, then steaming and boiling for 120 minutes by steam, filtering by a 300-mesh sieve, and collecting filtrate for later use; and secondly, adding 8 times of purified water, cooking for 96 minutes, filtering by using a 300-mesh sieve, and collecting filtrate for later use. And combining the two filtrates, concentrating under reduced pressure to obtain a concentrated solution with a relative density of 1: 1.2 obtaining 6kg of extract (namely tuckahoe extract);
s3, drying Poria extract, pulverizing, sieving with 60 mesh sieve, adding isomaltooligosaccharide, fructo-oligosaccharide, edible glucose, stachyose, Lactobacillus rhamnosus, and Bifidobacterium lactis, mixing, and drying;
and S4, subpackaging, and 5g in each bag.
Test example 1Sensory evaluation test
30 healthy volunteers aged 40-60 are selected to take the composition of the invention in example 1 at an amount of 2 times/day, 15g each time, for 14 consecutive days. The results of the sensory evaluation tests of the compositions of the present invention are shown in table 1.
Table 1 sensory evaluation test of the composition of example 1 of the invention
Figure BDA0002974495430000201
Test example 2Test for improving intestinal flora
1. Subject patient
60 subjects aged 40-60 years were selected, 40 of which were patients with intestinal disease and 20 of which were patients with parenteral disease. The tested patients do not take antibiotics, micro-ecological drinks or health care medicines within 1 month.
40 patients with intestinal disease were randomized into the trial group (20) and placebo group (20). 20 patients with parenteral disease were a control group. The subjects in the test group, the placebo group and the control group have no significant difference in age, sex, disease course, disease condition and the like (P > 0.05).
2. Experimental methods
The test group was administered a composition of the invention according to example 1 daily and the placebo group was administered a placebo daily at a dose of 10g per day at 2 times per day. The administration is continued for 14 days. The control group was dosed with equal amounts of water without any composition or placebo. During the test period, the subject diets were normal.
The number ratio (B/E value) of bifidobacteria to enterobacteria was calculated by measuring bifidobacteria and enterobacteria in the stools of the subjects (control group, test group, placebo group) 1 day before the test feeding and 14 days after the administration of the composition. The results are shown in Table 2.
TABLE 2 Change of intestinal flora before and after the test
Figure BDA0002974495430000211
n＝20)
Figure BDA0002974495430000212
Note: a the p of the test group after the test eating is less than 0.0 compared with the p of the test group before the test eating5； b After test feeding, comparing the p of the test group with that of the control group to be less than 0.05; c p is more than 0.05 after the placebo group takes the test meal compared with before the test meal.
Test example 3Efficacy comparison test
1. Test specimen
Selecting 40 cases of patients with intestinal diseases (with clinical symptoms of gastric acid, gastrectasia, constipation and diarrhea) of 40-60 years old, wherein the patients do not take antibiotics, microecological drinks or health care medicines within 1 month. 40 patients with intestinal diseases were randomly divided into a test group (20 cases) and a control group (20 cases). The experimental group and the control group have no significant difference in age, sex, disease course, disease condition and the like (P > 0.05).
2. Experimental method
The test group was administered the composition of example 1 of the present invention daily, and the control group was administered the composition of comparative example 1 daily in an amount of 10g per 2 times per day. The administration is continued for 14 days. During the test period, the subject diets were normal. The subjects were tested for clinical symptoms 6 days before the start of the test and 14 days after the administration of the composition.
3. Results of the experiment
The curative effect is standard. The effect is shown: most symptoms disappear, the life quality is basically maintained, and the main inspection indexes are basically normal after reexamination; the method has the following advantages: various symptoms and positive signs are improved compared with those before treatment, and main examination indexes are rechecked and improved; and (4) invalidation: compared with the prior treatment, the method has no progress in all aspects.
The data are expressed as mean ± standard deviation (X ± S), the count data are tested by X2, the grade data are analyzed by Ridit, and the measurement data are tested by t. The results are shown in Table 3.
TABLE 3
Figure BDA0002974495430000221
Note: p <0.01
The above description of the specific embodiments of the present invention is not intended to limit the present invention, and those skilled in the art may make various changes and modifications according to the present invention without departing from the spirit of the present invention, which is defined in the appended claims.

Claims (10)

1. The pharmaceutical composition containing the high-substitution-degree carboxymethyl pachyman is characterized by comprising the following components in parts by weight: 0.5-3 parts of tuckahoe, 5-12 parts of prebiotics and 0.005-0.03 part of probiotics.
2. The composition of claim 1, wherein the poria cocos in the composition is any one of pachymaran alkalized extract, pachymaran, and high-substitution-degree carboxymethyl pachymaran (CMP), preferably, the preparation method of the high-substitution-degree carboxymethyl pachymaran comprises the following steps: 1) adding pachymaran into water or water-alcohol mixed solution, stirring, adding alkaline solution with a mass of 1-8% of pachymaran, and stirring to completely dissolve to obtain pachymaran alkalized solution; 2) and (2) after fully reacting 1.0-10mol/L chloroacetic acid with proper excess 2.0-10mol/L alkaline solution, adding the obtained product into the pachyman alkalization solution obtained in the step 1), and performing substitution reaction, separation and purification to obtain the pachyman alkalization solution, wherein the proper excess is that the actual dosage of alkaline substances in the alkaline solution is 0.5-40% more than the theoretical dosage required by the neutralization reaction between the alkaline substances and chloroacetic acid.
3. The composition according to any one of claims 1-2, wherein the probiotic bacteria are selected from any one of bifidobacteria, bacillus subtilis, rhamnosus, bifidobacterium lactis, or a combination thereof.
4. The composition according to any one of claims 1 to 3, wherein the composition comprises 2 to 4 parts by weight of isomaltose, 2 to 4 parts by weight of fructo-oligosaccharide, 1 to 3 parts by weight of glucose, 1 to 3 parts by weight of Poria cocos, 0.5 to 1 part by weight of stachyose, 0.006 to 0.008 part by weight of rhamnosus bacteria and 0.006 to 0.008 part by weight of Bifidobacterium lactis.
5. The composition according to any one of claims 1 to 4, wherein the composition comprises 2 parts by weight of isomaltooligosaccharide, 2 parts by weight of fructooligosaccharide, 1 part by weight of glucose, 1 part by weight of Poria cocos, 0.5 part by weight of stachyose, 0.006 part by weight of rhamnosus bacteria and 0.006 part by weight of Bifidobacterium lactis bacteria.
6. The composition according to any one of claims 1 to 5, wherein the composition further comprises a desired amount of a pharmaceutically acceptable carrier, preferably wherein the pharmaceutically acceptable carrier is selected from any one of or a combination of fillers, lubricants, dispersants, wetting agents, binders, regulators, solubilizers, antioxidants, emulsifiers, flavoring agents, and perfuming agents.
7. The composition according to any one of claims 1 to 6, wherein the composition is an oral preparation, preferably, the oral preparation is selected from any one of oral liquid, syrup, suspension, tablet, capsule, granule, pill, powder, drop pill, mixture, lotion, effervescent agent, paste, emulsion and tea.
8. A process for the preparation of a composition according to any one of claims 1 to 7, comprising in particular the steps of:
s1, the Poria is selected from pachymaran alkalizing extractive solution, pachymaran, and high-substitution degree carboxymethyl pachymaran (CMP);
s2, drying any one of pachymaran alkalizing extract, pachymaran, and high-substitution-degree carboxymethyl pachymaran (CMP), pulverizing, sieving, adding desired amount of prebiotics, probiotics and pharmaceutically acceptable carrier, mixing, and drying.
9. Use of the composition according to any one of claims 1 to 7 or the composition prepared by the preparation method according to claim 8 for preparing a product for improving gastrointestinal function, preferably, the gastrointestinal function is selected from any one of immunity enhancement, anti-tumor, anti-virus, anti-radiation, liver protection, anti-bacteria, diuresis, sleep improvement, blood sugar reduction, blood fat reduction, anti-aging, anti-fatigue, constipation and gastrointestinal inflammation and dyspepsia prevention.
10. A pharmaceutical composition comprising highly substituted carboxymethyl pachyman, wherein the composition is prepared from the composition according to any one of claims 1 to 7 or the preparation method according to claim 8, and is used in combination with any one or combination of fiber supplement, medicament and microecological preparation, preferably, the microecological preparation is selected from any one or combination of probiotics and prebiotics.
CN202110271881.0A 2021-03-12 2021-03-12 Pharmaceutical composition containing high-substitution-degree carboxymethyl pachyman and application thereof Pending CN115068509A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202110271881.0A CN115068509A (en) 2021-03-12 2021-03-12 Pharmaceutical composition containing high-substitution-degree carboxymethyl pachyman and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202110271881.0A CN115068509A (en) 2021-03-12 2021-03-12 Pharmaceutical composition containing high-substitution-degree carboxymethyl pachyman and application thereof

Publications (1)

Publication Number Publication Date
CN115068509A true CN115068509A (en) 2022-09-20

Family

ID=83240713

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202110271881.0A Pending CN115068509A (en) 2021-03-12 2021-03-12 Pharmaceutical composition containing high-substitution-degree carboxymethyl pachyman and application thereof

Country Status (1)

Country Link
CN (1) CN115068509A (en)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1970579A (en) * 2006-11-28 2007-05-30 戴甲木 High substitution degree carboxymethyl indianbread polysaccharide and its preparation method and uses
CN107874251A (en) * 2017-11-14 2018-04-06 广东健来福云健康科技股份有限公司 A kind of eight delicacies probiotic composition with strengthening the spleen and stomach benefit function of intestinal canal
CN111671791A (en) * 2020-05-25 2020-09-18 中山大学 Micro-ecological composition for improving constipation by targeting intestinal flora and preparation thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1970579A (en) * 2006-11-28 2007-05-30 戴甲木 High substitution degree carboxymethyl indianbread polysaccharide and its preparation method and uses
CN107874251A (en) * 2017-11-14 2018-04-06 广东健来福云健康科技股份有限公司 A kind of eight delicacies probiotic composition with strengthening the spleen and stomach benefit function of intestinal canal
CN111671791A (en) * 2020-05-25 2020-09-18 中山大学 Micro-ecological composition for improving constipation by targeting intestinal flora and preparation thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
陈龙;郭晓晖;李富华;夏春燕;明建;: "食用菌膳食纤维功能特性及其应用研究进展", 食品科学, no. 11, pages 303 - 307 *

Similar Documents

Publication Publication Date Title
CN107156587A (en) Active probiotic solid beverage and its treatment diabetes B in apply
CN113519631B (en) Low-blood-sugar-load middle-aged and elderly-people modified milk powder for assisting in reducing blood sugar and preparation method thereof
CN110623182A (en) Probiotic plant solid beverage for treating hyperuricemia and gout
CN103608025B (en) For preventing or treat the compositions comprising herb extracts of neurodegenerative diseases
CN111227261A (en) Prebiotic composition and application thereof
CN114831286B (en) Composition with constipation relieving function and preparation method thereof
KR101614574B1 (en) Composition of Diabetes-Improving Effective Constituents by Fermentation Products of the Trifoliate Orange
CN108157971A (en) A kind of chitosan oligosaccharide liquid oral medicine and preparation method thereof
CN115281345A (en) Application of composite probiotic composition in combination with dimethylguanidine to treatment of type II diabetes
CN110710660A (en) Blood sugar lowering composition and dietary supplement containing bitter gourd powder
CN108186688B (en) Composition for promoting sleep
CN112931883A (en) Prebiotic composition and preparation method and application thereof
CN115068509A (en) Pharmaceutical composition containing high-substitution-degree carboxymethyl pachyman and application thereof
CN110448569B (en) Composition with antidiarrheal effect, preparation method and application thereof
CN115226773A (en) Composite probiotic sleep-aiding solid beverage and preparation method thereof
CN110559310B (en) Composition with constipation preventing and treating effects and preparation method and application thereof
CN104435100A (en) Anti-depression composition
CN115245525A (en) Poria cocos vitamin C pharmaceutical composition with effect of improving dental ulcer
CN108685981A (en) A kind of notoginseng-red sage capsule and preparation method thereof
WO2019218537A1 (en) Chitosan composition and preparation method therefor
CN115245197A (en) Poria cocos jelly for regulating intestines and stomach as well as preparation method and application of poria cocos jelly
KR102609638B1 (en) Composition comprising underia pinnatifida sporophyll hot-water extract for improving gut microbiome
CN115245548A (en) Green-money poria cocos medicinal composition with blood sugar reducing effect and application thereof
WO2021111980A1 (en) Prophylactic or ameliorating agent for orthostatic hypotension, and composition containing same
CN115245542A (en) Male flower cordyceps and poria cocos medicinal composition with sub-health improving effect

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination