WO2017129058A1 - 一种用于治疗痛风的药物 - Google Patents

一种用于治疗痛风的药物 Download PDF

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Publication number
WO2017129058A1
WO2017129058A1 PCT/CN2017/071864 CN2017071864W WO2017129058A1 WO 2017129058 A1 WO2017129058 A1 WO 2017129058A1 CN 2017071864 W CN2017071864 W CN 2017071864W WO 2017129058 A1 WO2017129058 A1 WO 2017129058A1
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parts
protein
weight
glycoprotein
drug
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PCT/CN2017/071864
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English (en)
French (fr)
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徐宝贞
程潜
程龙
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徐宝贞
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Priority to RS20220488A priority Critical patent/RS63233B1/sr
Priority to LTEPPCT/CN2017/071864T priority patent/LT3406258T/lt
Priority to EP17743673.0A priority patent/EP3406258B1/en
Priority to PL17743673T priority patent/PL3406258T3/pl
Priority to SI201731159T priority patent/SI3406258T1/sl
Priority to US16/074,011 priority patent/US10653746B2/en
Priority to DK17743673.0T priority patent/DK3406258T3/da
Priority to ES17743673T priority patent/ES2914280T3/es
Priority to HRP20220667TT priority patent/HRP20220667T1/hr
Publication of WO2017129058A1 publication Critical patent/WO2017129058A1/zh

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7012Compounds having a free or esterified carboxyl group attached, directly or through a carbon chain, to a carbon atom of the saccharide radical, e.g. glucuronic acid, neuraminic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/02Algae
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/19Acanthaceae (Acanthus family)
    • A61K36/195Strobilanthes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/21Amaranthaceae (Amaranth family), e.g. pigweed, rockwort or globe amaranth
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/31Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
    • A61K36/315Isatis, e.g. Dyer's woad
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/48Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/70Polygonaceae (Buckwheat family), e.g. spineflower or dock
    • A61K36/704Polygonum, e.g. knotweed
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/898Orchidaceae (Orchid family)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/04Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/10Peptides having 12 to 20 amino acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/04Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/14Peptides containing saccharide radicals; Derivatives thereof, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/06Antigout agents, e.g. antihyperuricemic or uricosuric agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/02Algae
    • A61K36/05Chlorophycota or chlorophyta (green algae), e.g. Chlorella

Definitions

  • the invention relates to a medicine for treating gout, and belongs to the technical field of medicine.
  • Gout is a disease caused by a disorder of sputum metabolism.
  • Clinical manifestations of hyperuricemia and uric acid crystal deposition caused by characteristic acute arthritis, tophi formation, tocstone chronic arthritis, and can occur urate nephropathy, urinary acid urinary tract stones, etc. Joint disability and renal insufficiency may occur.
  • the prerequisite for the onset of gout is hyperuricemia. Therefore, hyperuricemia is the most important biochemical basis for gout, followed by uric acid deposition causing an inflammatory response.
  • the incidence of hyperuricemia and primary gout has increased year by year due to the increase in dietary structure, the increase in alcohol, especially beer, and the decrease in physical activity.
  • kidney disease which poses a greater risk to human health and has received widespread attention in the medical community.
  • Western medicine treats hyperuricemia and gout in stages.
  • Western medicine usually uses non-steroidal anti-inflammatory drugs (such as etoricoxib, celecoxib, etc.) and uric acid-lowering drugs (such as allopurinol, in the acute phase).
  • non-steroidal anti-inflammatory drugs such as etoricoxib, celecoxib, etc.
  • uric acid-lowering drugs such as allopurinol, in the acute phase.
  • Patent No. US2015337001 A1
  • the present invention relates to a purpura extract capable of preventing and improving hyperuricemia or gout It has the effect of inhibiting uric acid production and reducing its concentration.
  • the compositions are also disclosed for use in the treatment of gout and metabolic syndrome.
  • Patent A traditional Chinese medicine composition for treating gout, the patent number is CN201310601617.4, which discloses:
  • a traditional Chinese medicine composition for treating gout relates to a traditional Chinese medicine composition.
  • the invention aims to solve the problem that the western medicine for treating gout has great side effects on the human body and the symptoms are not cured.
  • the traditional Chinese medicine composition for treating gout of the present invention comprises 5-10 parts of Sophora flavescens, 10-15 parts of Epimedium, 5-10 parts of aconite, 4-8 parts of Chuanxiong and 8-12 parts of Shiwei by weight. , papaya 6 ⁇ 9 parts and 3 to 6 parts of Amomum villosum.
  • the traditional Chinese medicine composition for treating gout of the invention has small side effects on the human body, both the treatment and the standard, and has a good curative effect on treating gout, and the total clinical effective rate is 96.7%.
  • the invention is for the treatment of gout.
  • the present invention provides a medicament for treating gout to achieve the following objects:
  • the medicament of the invention has the characteristics of high efficiency, safety, no side effects, good therapeutic effect on human gout, total effective rate of 98%; low recurrence rate;
  • the medicament of the invention reduces the urine protein content of the rat gout model
  • the medicament of the invention reduces the creatinine content of the rat gout model
  • the medicament of the invention reduces the urea nitrogen content of the rat gout model
  • the drug of the present invention reduces the content of blood uric acid in a mouse hyperuricemia model.
  • the present invention adopts the following technical solutions:
  • a medicament for treating gout characterized in that the medicament is a glycoprotein, or a mixture or polypeptide or protein of a polysaccharide, the glycoprotein comprising 1-99% sugar, 1-99% protein;
  • a mixture of polysaccharides and proteins, by weight, comprises from 1 to 99% polysaccharide and from 1 to 99% protein.
  • the glycoprotein has a molecular weight of 0.2-3000 kDa;
  • the drug is a marine algae glycoprotein.
  • the marine algae glycoprotein comprises, by weight, 1-99% sugar, 1-99% protein; a mixture of the marine algae polysaccharide and protein, including by weight, 1-99%, protein 1- 99%.
  • the marine algae glycoprotein has a molecular weight of 0.2-3000 kDa;
  • the polysaccharide and protein mixture has a molecular weight of 0.2-3000 kDa
  • the protein has a molecular weight of 0.2-3000 kDa.
  • the drug comprises, by weight, 1-99 parts of glycoprotein and 1-25 parts of glucuronic acid.
  • the drug comprises, by weight, 1-99 parts of marine algae glycoprotein and 1-25 parts of glucuronic acid.
  • the drug in terms of weight, includes 1-99 parts of marine algae glycoprotein, 1-25 parts of glucuronic acid, and 2-9 parts of barley.
  • the algae is one or more of cyanobacteria, green algae, red algae, gold algae, and brown algae.
  • the drug comprises, by weight, 1-99 parts of marine algae glycoprotein, 8-14 parts of barley, and 7-13 parts of burdock.
  • the drug comprises, by weight, 1-99 parts of marine algae glycoprotein, 8-14 parts of barley, 7-13 parts of burdock, and 1-15 parts of glucuronic acid.
  • the drug by weight, includes 1-99% sugar and 1-99% protein.
  • the marine algae glycoprotein comprises, by weight, 1-99% sugar and 1-99% protein.
  • the medicine of the invention has a good therapeutic effect on human gout, the total effective rate is 98%, wherein the proportion of healing is 85%; the ratio of marked effect is 13%; the proportion of invalid is only 2%; The recurrence rate after 5 years is only 1%;
  • the drug of the invention reduces the urine protein content of the rat gout model; after 4 weeks of administration of the rat gout model, the urine protein value of the rat is 50.89-168.78 mg/L; The urine protein value was 364.83 mg/L;
  • the drug of the invention reduces the creatinine content of the rat gout model; after 4 weeks of administration of the rat gout model, the creatinine content of the rat is 152.45-172.82 mmol/L; the creatinine content of the model control group rats 288.01 mmol / L;
  • the drug of the invention reduces the urea nitrogen content of the rat gout model; after 4 weeks of administration of the rat gout model, the urea nitrogen content of the rat is 11.58-15.64 mmol/L; the model control group rats The urea nitrogen content is 56.07 mmol / L;
  • the drug of the present invention reduces blood uric acid content in a mouse hyperuricemia model, and the blood uric acid value of the mouse of the present invention is 147.89-160.5 ⁇ mol/L; in the model control group, the blood uric acid value of the mouse is 250.4 ⁇ mol/L.
  • Example 1 A drug for treating gout
  • the drug is a marine algae glycoprotein
  • the marine algae glycoprotein comprises, by weight, 1% sugar, 99% protein
  • the molecular weight is 0.2 kDa
  • the sugar is a polysaccharide
  • the marine algae is cyanobacteria
  • the polysaccharide comprises: glucose, galactose, mannose, rhamnose;
  • the protein includes: arginine, lysine, serine, threonine.
  • Example 2 A drug for treating gout
  • the drug is a marine algae glycoprotein
  • the marine algae glycoprotein which comprises 9% sugar and 88% protein by weight
  • the molecular weight is 3kDa
  • the sugar is a polysaccharide
  • the marine algae is: cyanobacteria
  • the polysaccharide comprises: glucose, galactose, mannose, rhamnose;
  • the protein includes: arginine, lysine, serine, threonine.
  • Example 3 A drug for treating gout
  • the drug is a marine algae glycoprotein
  • the marine algae glycoprotein which comprises, by weight, 16% sugar, 80% protein,
  • the molecular weight is 25kDa
  • the sugar is a polysaccharide
  • the marine algae is: chlorella;
  • the polysaccharide comprises: glucose, galactose, mannose, rhamnose;
  • the protein includes: arginine, lysine, serine, threonine.
  • Example 4 A drug for treating gout
  • the drug is a marine algae glycoprotein
  • the marine algae glycoprotein including 30% sugar, 70% protein, by weight
  • the molecular weight is 40kDa;
  • the sugar is a polysaccharide
  • the marine algae is: red algae;
  • the polysaccharide comprises: glucose, galactose, mannose, rhamnose;
  • the protein includes: arginine, lysine, serine, threonine.
  • Example 5 A drug for treating gout
  • the glycoprotein is a marine algae glycoprotein
  • the marine algae glycoprotein which comprises 50% by weight of sugar and 50% by weight of protein
  • the molecular weight is 100 kDa
  • the sugar is a polysaccharide
  • the marine algae is: brown algae;
  • the polysaccharide comprises: glucose, galactose, mannose, rhamnose;
  • the protein includes: arginine, lysine, serine, threonine.
  • Example 6 A drug for treating gout
  • the glycoprotein is a marine algae glycoprotein
  • the marine algae glycoprotein by weight, comprises 99% sugar, 1% protein,
  • the molecular weight is 3000kDa
  • the sugar is a polysaccharide
  • the marine algae is: gold algae;
  • the polysaccharide comprises: glucose, galactose, mannose, rhamnose;
  • the protein includes: arginine, lysine, serine, threonine.
  • glycoprotein according to any of the above embodiments 1-6, further comprising a pigment;
  • the pigment is a natural pigment contained in the algae substance;
  • the drug is a glycoprotein
  • the glycoprotein by weight content, comprises 1-99% sugar, 1-99% protein
  • the molecular weight is 0.2-30000 kDa
  • the sugar is a polysaccharide
  • the drugs include synthetic glycoproteins and synthetic polysaccharides and proteins.
  • the protein comprises 20 amino acids and 8 synthetic amino acids
  • the preparation method of the medicine the glycoprotein is prepared into capsules, tablets and the like according to a conventional process; the mixture of the polysaccharide and the protein is formed into capsules, tablets and the like according to a conventional process.
  • the gout was induced by streptozotocin, and then the group prepared by the present invention was fed with the drug prepared by the present invention, administered intragastrically three times a day, the control group was fed with distilled water, and the rats were measured four weeks later.
  • the value of urinary protein, creatinine and urea nitrogen were as shown in Table 1 and Table 2.
  • Example 2 and Example 3 are preferred embodiments.
  • mice were randomly divided into 8 groups after entering the laboratory, namely normal control group, model control group, and 1-6 groups of the present invention, 10 rats in each group, weighing and numbering;
  • the normal control group and the model control group were intragastrically administered with distilled water, and the present invention group 1-6 was administered to the present invention.
  • the drug was administered at a dose of 3 g/day and administered intragastrically three times a day for 3 consecutive days.
  • Example 2 and Example 3 are preferred embodiments.
  • the recurrence rate is low, and the recurrence rate of the recovered person after 5 years is only 1%.
  • Example 8 A drug for treating gout
  • the marine algae glycoprotein which comprises 9% sugar and 88% protein by weight
  • the molecular weight is 8kDa
  • the sugar is a polysaccharide
  • the marine algae is: spirulina
  • the polysaccharide comprises: glucose, galactose, mannose, rhamnose;
  • the protein includes: arginine, lysine, serine, threonine.
  • Example 9 A drug for treating gout
  • the marine algae glycoprotein which comprises 9% sugar and 88% protein by weight
  • the molecular weight is 12kDa
  • the sugar is a polysaccharide
  • the marine algae is: chlorella;
  • the polysaccharide comprises: glucose, galactose, mannose, rhamnose;
  • the protein includes: arginine, lysine, serine, threonine.
  • Example 10 A drug for treating gout
  • the marine algae glycoprotein including 30% sugar, 70% protein, by weight
  • the molecular weight is 20kDa;
  • the sugar is a polysaccharide
  • the marine algae is: hair dish;
  • the polysaccharide comprises: glucose, galactose, mannose, rhamnose;
  • the protein includes: arginine, lysine, serine, threonine.
  • Example 11 A drug for treating gout
  • the marine algae glycoprotein which comprises 50% by weight of sugar and 50% by weight of protein
  • the molecular weight is 8kDa
  • the sugar is a polysaccharide
  • the marine algae is: Sargassum;
  • the polysaccharide comprises: glucose, galactose, mannose, rhamnose;
  • the protein includes: arginine, lysine, serine, threonine.
  • Embodiment 12 A drug for treating gout
  • the marine algae glycoprotein by weight, comprises 99% sugar, 1% protein,
  • the molecular weight is 20kDa;
  • the sugar is a polysaccharide
  • the marine algae is: yellow algae;
  • the polysaccharide comprises: glucose, galactose, mannose, rhamnose;
  • the protein includes: arginine, lysine, serine, threonine.
  • Example 13 A drug for treating gout
  • the marine algae glycoprotein which comprises 9% sugar and 88% protein by weight
  • the molecular weight is 6kDa
  • the sugar is a polysaccharide
  • the marine algae is: cyanobacteria
  • the polysaccharide comprises: glucose, galactose, mannose, rhamnose;
  • the protein includes: arginine, lysine, serine, threonine.
  • Embodiment 14 A drug for treating gout
  • the marine algae glycoprotein which comprises 9% sugar and 88% protein by weight
  • the molecular weight is 20kDa;
  • the sugar is a polysaccharide
  • the marine algae is: cyanobacteria
  • the polysaccharide comprises: glucose, galactose, mannose, rhamnose;
  • the protein includes: arginine, lysine, serine, threonine.
  • Embodiment 15 A drug for treating gout
  • the marine algae glycoprotein including 30% sugar, 70% protein, by weight
  • the molecular weight is 200kDa
  • the sugar is a polysaccharide
  • the marine algae is: cyanobacteria
  • the polysaccharide comprises: glucose, galactose, mannose, rhamnose;
  • the protein includes: arginine, lysine, serine, threonine.
  • Embodiment 16 A drug for treating gout
  • the marine algae glycoprotein which comprises 50% by weight of sugar and 50% by weight of protein
  • the molecular weight is 3000kDa
  • the sugar is a polysaccharide
  • the marine algae is: cyanobacteria
  • the polysaccharide comprises: glucose, galactose, mannose, rhamnose;
  • the protein includes: arginine, lysine, serine, threonine.
  • Example 7 Using the test method described in Example 7, the present invention is the drug described in Example 8 to Example 16, and the application effect is as follows:
  • the recurrence rate is low, and the recurrence rate of the recovered person after 6 years is only 1%.
  • Example 17 A drug for treating gout
  • the marine algae glycoprotein which comprises 10% sugar, 85% protein, by weight,
  • the molecular weight is 16kDa
  • the sugar is a polysaccharide
  • the marine algae is: spirulina
  • the polysaccharide comprises: glucose, galactose, mannose, rhamnose;
  • the protein includes: arginine, lysine, serine, threonine.
  • Embodiment 18 A drug for treating gout
  • the marine algae glycoprotein which comprises 8% sugar and 88% protein by weight
  • the molecular weight is 14kDa
  • the sugar is a polysaccharide
  • the marine algae is: chlorella;
  • the polysaccharide comprises: glucose, galactose, mannose, rhamnose;
  • the protein includes: arginine, lysine, serine, threonine.
  • Example 19 A drug for treating gout
  • the marine algae glycoprotein including 30% sugar, 70% protein, by weight
  • the molecular weight is 38kDa
  • the sugar is a polysaccharide
  • the marine algae is: broccoli;
  • the polysaccharide comprises: glucose, galactose, mannose, rhamnose;
  • the protein includes: arginine, lysine, serine, threonine.
  • Embodiment 20 A drug for treating gout
  • It includes 1 part of marine algae glycoprotein, 8 parts of barley, 7 parts of burdock, and 1 part of glucuronic acid.
  • the marine algae glycoprotein which comprises 10% sugar, 85% protein, by weight,
  • the molecular weight is 16kDa
  • the sugar is a polysaccharide
  • the marine algae is: spirulina
  • the polysaccharide comprises: glucose, galactose, mannose, rhamnose;
  • the protein includes: arginine, lysine, serine, threonine.
  • Embodiment 21 A drug for treating gout
  • the marine algae glycoprotein which comprises 8% sugar and 88% protein by weight
  • the molecular weight is 14kDa
  • the sugar is a polysaccharide
  • the marine algae is: chlorella;
  • the polysaccharide comprises: glucose, galactose, mannose, rhamnose;
  • the protein includes: arginine, lysine, serine, threonine.
  • Embodiment 22 A drug for treating gout
  • the marine algae glycoprotein including 30% sugar, 70% protein, by weight
  • the molecular weight is 200kDa
  • the sugar is a polysaccharide
  • the marine algae is: broccoli;
  • the polysaccharide comprises: glucose, galactose, mannose, rhamnose;
  • the protein includes: arginine, lysine, serine, threonine.
  • Example 7 Using the test method described in Example 7, the present invention is the drug described in Example 17 to Example 22, and the application effect is as follows:
  • the recurrence rate was low, and there was no recurrence after 5 years of recovery.
  • Example 23 A drug for treating gout
  • the marine algae glycoprotein which comprises 10% sugar, 85% protein, by weight,
  • the molecular weight is 15kDa
  • the marine algae is: green algae;
  • the sugar in parts by weight, comprises the following components: 8 parts of glucose, 5 parts of galactose, 11 parts of mannose;
  • the protein in parts by weight, includes the following components: 7 parts of serine, 9 parts of threonine, and 15 parts of hydroxylysine.
  • Embodiment 24 A drug for treating gout
  • the marine algae glycoprotein which comprises, by weight, 12% sugar, 75% protein,
  • the molecular weight is 8kDa
  • the marine algae is: cyanobacteria
  • the sugar in parts by weight, comprises the following components: 20 parts of glucose, 8 parts of galactose, 15 parts of mannose;
  • the protein in parts by weight, includes the following components: 10 parts of serine, 15 parts of threonine, and 17 parts of hydroxylysine.
  • Embodiment 25 A drug for treating gout
  • the marine algal glycoprotein comprises, by weight, 14% sugar, 72% protein,
  • the molecular weight is 20kDa;
  • the marine algae is: cyanobacteria
  • the sugar in parts by weight, comprises the following components: 20 parts of glucose, 8 parts of galactose, 15 parts of mannose;
  • the protein in parts by weight, includes the following components: 10 parts of serine, 15 parts of threonine, and 17 parts of hydroxylysine.
  • Embodiment 26 A drug for treating gout
  • the marine algal glycoprotein comprises, by weight, 22% sugar and 69% protein
  • the molecular weight is 100 kDa
  • the marine algae is: cyanobacteria
  • the sugar in parts by weight, comprises the following components: 20 parts of glucose, 8 parts of galactose, 15 parts of mannose;
  • the protein in parts by weight, includes the following components: 10 parts of serine, 15 parts of threonine, and 17 parts of hydroxylysine.
  • Example 27 A method for preparing a medicament for treating gout
  • Step 1 weighing
  • the Chinese medicine is pulverized into 100 mesh medicinal materials powder, 8 times the amount of 50% ethanol is added, and the control temperature is 60 ° C, 260 W micro Wave power, microwave wavelength of 130 mm, microwave radiation with a frequency of 1200 MHz for 5 min, filtration, collecting filtrate; separating the dregs, adding 6 volumes of clean water, controlling the temperature to 50 ° C, 200 W microwave power, microwave wavelength 140 mm , microwave irradiation at a frequency of 1250 MHz for 5 min, filtration, and collecting the filtrate;
  • the two filtrates are combined and spray-dried to obtain a Chinese medicine powder
  • the marine algae glycoprotein powder is combined with the above-mentioned prepared Chinese medicine powder and mixed to prepare a capsule, a tablet or the like.
  • Example 7 Using the test method described in Example 7, the present invention is the drug described in Example 23 to Example 26, and the application effect is as follows:
  • the recurrence rate was low, and there was no recurrence after 5 years of recovery.
  • the medicament of the present invention has a pH of between 5.3 and 9.8, preferably between 6.5 and 7.5.
  • the invention has been subjected to a large number of tests, and the invention has been carried out by performing a plurality of tests on a mixture of marine shells, bones of livestock and poultry, glycoprotein extracted from the skeleton of marine animals, and polysaccharides and proteins.
  • Embodiment 28 A drug for treating gout
  • the drug is a mixture of polysaccharides and proteins
  • the drug in parts by weight, comprises 1-99% polysaccharide, 1-99% protein;
  • the polysaccharide comprises: glucose, galactose, mannose, rhamnose;
  • the protein comprises: arginine, lysine, serine, threonine;
  • the polysaccharide and protein mixture has a molecular weight of 0.2-3000 kDa
  • the protein has a molecular weight of 0.2-3000 kDa.
  • the pigment is a natural pigment contained in an algae substance
  • the algal protein may be phycocyanin, phycoerythrin or phycoerythrin.
  • the glycoproteins include synthetic glycoproteins and synthetic polysaccharides and proteins.
  • the drug of the invention has a non-toxic dose of 1.6 g/kg for oral administration for dogs for 12 weeks, which is equivalent to 50 times of the equivalent dose for humans, so the safety of the clinical test can be considered to be guaranteed.
  • the medicament of the present invention may also be a health care product or a food.

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Abstract

本发明提供一种用于治疗痛风的药物,所述药物为糖蛋白或多糖和蛋白质的混合物或多肽或蛋白。

Description

一种用于治疗痛风的药物 技术领域
本发明涉及一种用于治疗痛风的药物,属于医药技术领域。
背景技术
痛风是一种由于嘌呤代谢紊乱所导致的疾病。临床表现为高尿酸血症和尿酸盐结晶沉积所致的特征性急性关节炎、痛风石形成、痛风石性慢性关节炎,并可发生尿酸盐肾病、尿酸性尿路结石等,严重者可出现关节致残、肾功能不全。痛风发病的先决条件是高尿酸血症,因此,高尿酸血症是痛风最重要的生化基础,其次是尿酸盐沉积引起炎性反应。随着人们生活水平的提高,近年来由于饮食结构的改变,酒精尤其是啤酒类饮品的摄入增加以及体力活动量的减少,导致高尿酸血症和原发性痛风的发病率呈逐年上升趋势,且发病年龄呈现低龄化。该病由于尿酸在血中呈现过饱和状态,除了对骨、关节造成直接损害外,还会沉积在肾脏引起肾病变,对人体健康的危害存在较大的危险,受到了医学界的广泛关注。
目前,西医对高尿酸血症和痛风的治疗采用分期进行,西医在急性期通常采用非甾体抗炎药(如依托考昔、塞来昔布等)、降尿酸药(如别嘌醇、非布索坦、丙磺舒、苯溴马隆等)、糖皮质激素和秋水仙碱等,间歇期和慢性期的治疗常采用饮食控制和降尿酸药治疗,虽然非甾体抗炎药可以迅速控制痛风的极性发作,该药物在痛风的发作期只起到止痛作用,但止痛不治病,治标不治本,难以根治,并且这些药物存在较严重的毒副作用。
专利:ASTER GLEHNI EXTRACTS,FRACTIONS OR COMPOUNDS ISOLATED THEREFROM FOR THE TREATMENT OR PREVENTION OF HYPERURICEMIA OR GOUT专利号为US2015337001(A1),公开了:本发明涉及一种紫菀提取物,能够预防和改善高尿酸血症或痛风,具有抑制尿酸生成,并降低其浓度的影响。
专利:THE USE OF BUCILLAMINE IN THE TREATMENT OF GOUT,专利号为US2015306054(A1),公开了:药物组合物包括布西拉明和别嘌呤醇或秋水仙碱,或其药用盐或溶剂化物,以及一种或多种药学上可接受的载体、稀释剂和赋形剂。还公开了所述组合物用于痛风和代谢综合征的治疗。
专利:一种治疗痛风的中药组合物,专利号为CN201310601617.4,公开了:
一种治疗痛风的中药组合物,它涉及一种中药组合物。本发明要解决现有治疗痛风的西药对人体副作用大以及治标不治本的问题。本发明的一种治疗痛风的中药组合物按重量份数是由苦参5~10份、淫羊藿10~15份、附子5~10份、川芎4~8份、石韦8~12份、木瓜6~ 9份和砂仁3~6份制成。本发明治疗痛风的中药组合物对人体副作用小,既治标又治本,并且对于治疗痛风有较好的疗效,临床总有效率达96.7%。本发明用于痛风的治疗。
中药用于治疗痛风的作用机理复杂,临床疗效不确切,目前尚无临床上被推荐用于治疗痛风的中成药,国内痛风患者基本依赖西药治疗。
发明内容:
本发明为解决现有技术中存在的不足,提供一种用于治疗痛风的药物,以实现以下发明目的:
(1)本发明所述药物,其特点,高效、安全、无副作用,对人体痛风有较好的治疗效果,总有效率达98%;复发率低;
(2)本发明所述药物,降低大鼠痛风模型的尿蛋白含量;
(3)本发明所述药物,降低大鼠痛风模型的肌酐含量;
(4)本发明所述药物,降低大鼠痛风模型的的尿素氮含量;
(5)本发明所述药物,降低小鼠高尿酸血症模型中血尿酸的含量。
为解决以上技术问题,本发明采用如下技术方案:
一种用于治疗痛风的药物,其特征在于:所述药物为糖蛋白,或多糖和蛋白质的混合物或多肽或蛋白,所述糖蛋白包括糖1-99%,蛋白质1-99%;所述多糖和蛋白质的混合物,以重量含量计,包括多糖1-99%,蛋白质1-99%。所述糖蛋白,分子量为0.2-3000kDa;
以下是对上述技术方案的进一步改进:
所述药物为海洋藻类糖蛋白。
所述海洋藻类糖蛋白,以重量含量计,包括糖1-99%,蛋白质1-99%;所述海洋藻类多糖和蛋白质的混合物,以重量含量计,包括多糖1-99%,蛋白质1-99%。
所述海洋藻类糖蛋白,分子量为0.2-3000kDa;
所述多糖和蛋白质的混合物,多糖的分子量为0.2-3000kDa,蛋白质的分子量为0.2-3000kDa。
所述药物,以重量含量计,包括糖蛋白1-99份、葡萄糖醛酸1-25份。
所述药物,以重量含量计,包括海洋藻类糖蛋白1-99份、葡萄糖醛酸1-25份。
所述药物,以重量含量计,包括海洋藻类糖蛋白1-99份、葡萄糖醛酸1-25份、青黛2-9份。
所述藻类为蓝藻、绿藻、红藻、金藻、褐藻中的一种或多种。
所述药物,以重量含量计,包括海洋藻类糖蛋白1-99份、青黛8-14份、牛蕂7-13份。
所述药物,以重量含量计,包括海洋藻类糖蛋白1-99份、青黛8-14份、牛蕂7-13份、葡萄糖醛酸1-15份。
所述药物,以重量含量计,包括糖1-99%,蛋白质1-99%。
所述海洋藻类糖蛋白,以重量含量计,包括糖1-99%,蛋白质1-99%。
相对现有技术,本发明的有益效果为:
(1)本发明所述药物,对人体痛风有较好的治疗效果,总有效率为98%,其中痊愈的比例为85%;显效的比例为13%;无效的比例仅为2%;痊愈者,5年后的复发率仅为1%;
(2)本发明所述药物,降低大鼠痛风模型的尿蛋白含量;对大鼠痛风模型给药4四周后,大鼠的尿蛋白值为50.89-168.78mg/L;模型对照组大鼠的尿蛋白值为364.83mg/L;
(3)本发明所述药物,降低大鼠痛风模型的肌酐含量;对大鼠痛风模型给药4四周后,大鼠的肌酐含量为152.45-172.82mmol/L;模型对照组大鼠的肌酐含量为288.01mmol/L;
(4)本发明所述药物,降低大鼠痛风模型的的尿素氮含量;对大鼠痛风模型给药4四周后,大鼠的尿素氮含量为11.58-15.64mmol/L;模型对照组大鼠的尿素氮含量为56.07mmol/L;
(5)本发明所述药物,降低小鼠高尿酸血症模型中血尿酸的含量,喂食本发明小鼠血尿酸值为147.89-160.5μmol/L;模型对照组,小鼠的血尿酸值为250.4μmol/L。
具体实施方式
以下对本发明的优选实施例进行说明,应当理解,此处所描述的优选实施例仅用于说明和解释本发明,并不用于限定本发明。
实施例1一种用于治疗痛风的药物
所述药物,为海洋藻类糖蛋白;
所述海洋藻类糖蛋白,以重量含量计,包括糖1%,蛋白质99%;
分子量为0.2kDa;
所述糖为多糖;
所述海洋藻类为蓝藻;
所述多糖,包括:葡萄糖、半乳糖、甘露糖、鼠李糖;
所述蛋白质,包括:精氨酸、赖氨酸、丝氨酸、苏氨酸。
实施例2一种用于治疗痛风的药物
所述药物为海洋藻类糖蛋白;
所述海洋藻类糖蛋白,以重量含量计,包括糖9%,蛋白质88%,
分子量为3kDa;
所述糖为多糖;
所述海洋藻类为:蓝藻;
所述多糖,包括:葡萄糖、半乳糖、甘露糖、鼠李糖;
所述蛋白质,包括:精氨酸、赖氨酸、丝氨酸、苏氨酸。
实施例3一种用于治疗痛风的药物
所述药物为海洋藻类糖蛋白;
所述海洋藻类糖蛋白,以重量含量计,包括糖16%,蛋白质80%,
分子量为25kDa;
所述糖为多糖;
所述海洋藻类为:小球藻;
所述多糖,包括:葡萄糖、半乳糖、甘露糖、鼠李糖;
所述蛋白质,包括:精氨酸、赖氨酸、丝氨酸、苏氨酸。
实施例4一种用于治疗痛风的药物
所述药物为海洋藻类糖蛋白;
所述海洋藻类糖蛋白,以重量含量计,包括糖30%,蛋白质70%,
分子量为40kDa;
所述糖为多糖;
所述海洋藻类为:红藻;
所述多糖,包括:葡萄糖、半乳糖、甘露糖、鼠李糖;
所述蛋白质,包括:精氨酸、赖氨酸、丝氨酸、苏氨酸。
实施例5一种用于治疗痛风的药物
所述糖蛋白为海洋藻类糖蛋白;
所述海洋藻类糖蛋白,以重量含量计,包括糖50%,蛋白质50%,
分子量为100kDa;
所述糖为多糖;
所述海洋藻类为:褐藻;
所述多糖,包括:葡萄糖、半乳糖、甘露糖、鼠李糖;
所述蛋白质,包括:精氨酸、赖氨酸、丝氨酸、苏氨酸。
实施例6一种用于治疗痛风的药物
所述糖蛋白为海洋藻类糖蛋白;
所述海洋藻类糖蛋白,以重量含量计,包括糖99%,蛋白质1%,
分子量为3000kDa;
所述糖为多糖;
所述海洋藻类为:金藻;
所述多糖,包括:葡萄糖、半乳糖、甘露糖、鼠李糖;
所述蛋白质,包括:精氨酸、赖氨酸、丝氨酸、苏氨酸。
上述实施例1-6所述的糖蛋白,还包括色素;所述色素为藻类物质中含有的天然色素;
对上述实施例1-6进行概括为:
一种用于治疗痛风的药物
所述药物,为糖蛋白;
所述糖蛋白,以重量含量计,包括糖1-99%,蛋白质1-99%;
分子量为0.2-30000kDa;
所述糖为多糖;
所述药物,包括合成糖蛋白及合成多糖和蛋白质。
所述蛋白包括20种氨基酸和8种人工合成氨基酸;
所述药物的制备方法:糖蛋白按照常规工艺制成胶囊、片剂等;多糖和蛋白的混合物按照常规工艺制成胶囊、片剂等。
实施例7所述药物在治疗痛风中的应用
(1)本发明药物对链尿佐菌素致大鼠痛风模型的治疗效果
模型对照组和本发明组,先采用链尿佐菌素致大鼠痛风,然后本发明组喂食本发明制备的药物,一天分3次灌胃给药,对照组喂食蒸馏水,四周后测定大鼠中尿蛋白值、肌酐、尿素氮含量,结果见表1、表2。
表1本发明药物对链尿佐菌素致大鼠痛风模型的影响
[根据细则26改正13.03.2017] 
Figure WO-DOC-TABLE-1
实施例2和实施例3是优选实施例。
表2本发明药物不同剂量对链尿佐菌素致大鼠痛风模型的影响
[根据细则26改正13.03.2017] 
Figure WO-DOC-TABLE-2
(2)本发明药物对黄嘌呤致小鼠高尿酸血症模型的治疗效果
A、实验材料
动物:清洁级昆明种小鼠50只,雄性,20g±2g
药物:实施例1-6所述药物
黄嘌呤:国药集团化学试剂有限公司,批号WL20101109
血尿酸检测试剂盒:上海荣盛生物技术有限公司,批号20100406
B、实验方法
小鼠进实验室后随机分为8组,即正常对照组、模型对照组、本发明组1-6,每组10只,称重并编号;
适应性喂养1周后,正常对照组、模型对照组灌胃给予蒸馏水,本发明组1-6,给予本发明 所述药物,剂量为3g/天,灌胃给药,每天3次,连续3天。
末次灌胃后1h,正常对照组腹腔注射生理盐水0.1mL/10g,其余7组腹腔注射10%黄嘌呤混悬液0.1mL/10g进行造模,0.5h后用摘眼球法取血检测尿酸值并对测定结果进行统计分析,实验结果见表3。
表3本发明药物对小鼠高尿酸血症模型血尿酸的影响
Figure PCTCN2017071864-appb-000003
实施例2和实施例3是优选实施例。
表4本发明药物不同剂量对小鼠高尿酸血症模型血尿酸的影响
Figure PCTCN2017071864-appb-000004
(3)人体临床试验
人体临床试验如下:
试验病例共100例,其中男性52例,女性48例,年龄最小32岁,最大61岁,病程最短6个月,最长8年,以3~5年最多;其中第一跖趾关节肿痛者一侧50例,两侧50例;其中单侧关节炎60例,两个关节疼痛发炎者40例;其中有痛风石者10例。所有病例均通过检 查,并且100例全部有血尿酸增高,所有患者排除药物及其他疾病继发。
治疗方法:
均采用实施例3制备的治疗痛风的药物,每日3g,分3次给药,每日3次,温开水冲服。21天个月为一个疗程,一般服用一个疗程,疗程结束观察疗效。疗效评定标准:
痊愈:临床症状全部消失,关节活动自如,血尿酸降至正常范围;显效:临床症状好转,关节活动灵活,血尿酸较前降低10%以上;无效:症状及实验室检查无变化。
结果:
痊愈:85例,占85%;
显效:13例,占13%;
无效:2例,占2%;
总有效率:98%;
复发率低,痊愈者5年后的复发率仅为1%。
实施例8一种用于治疗痛风的药物
以重量份计,包括以下组分:
海洋藻类糖蛋白1份、葡萄糖醛酸1份;
所述海洋藻类糖蛋白,以重量含量计,包括糖9%,蛋白质88%,
分子量为8kDa;
所述糖为多糖;
所述海洋藻类为:螺旋藻;
所述多糖,包括:葡萄糖、半乳糖、甘露糖、鼠李糖;
所述蛋白质,包括:精氨酸、赖氨酸、丝氨酸、苏氨酸。
实施例9一种用于治疗痛风的药物
以重量份计,包括以下组分:
海洋藻类糖蛋白15份、葡萄糖醛酸6份;
所述海洋藻类糖蛋白,以重量含量计,包括糖9%,蛋白质88%,
分子量为12kDa;
所述糖为多糖;
所述海洋藻类为:小球藻;
所述多糖,包括:葡萄糖、半乳糖、甘露糖、鼠李糖;
所述蛋白质,包括:精氨酸、赖氨酸、丝氨酸、苏氨酸。
实施例10一种用于治疗痛风的药物
以重量份计,包括以下组分:
海洋藻类糖蛋白40份、葡萄糖醛酸13份
所述海洋藻类糖蛋白,以重量含量计,包括糖30%,蛋白质70%,
分子量为20kDa;
所述糖为多糖;
所述海洋藻类为:头发菜;
所述多糖,包括:葡萄糖、半乳糖、甘露糖、鼠李糖;
所述蛋白质,包括:精氨酸、赖氨酸、丝氨酸、苏氨酸。
实施例11一种用于治疗痛风的药物
以重量份计,包括以下组分:
海洋藻类糖蛋白70份、葡萄糖醛酸17份;
所述海洋藻类糖蛋白,以重量含量计,包括糖50%,蛋白质50%,
分子量为8kDa;
所述糖为多糖;
所述海洋藻类为:马尾藻;
所述多糖,包括:葡萄糖、半乳糖、甘露糖、鼠李糖;
所述蛋白质,包括:精氨酸、赖氨酸、丝氨酸、苏氨酸。
实施例12一种用于治疗痛风的药物
以重量份计,包括以下组分:
海洋藻类糖蛋白99份、葡萄糖醛酸25份;
所述海洋藻类糖蛋白,以重量含量计,包括糖99%,蛋白质1%,
分子量为20kDa;
所述糖为多糖;
所述海洋藻类为:黄群藻;
所述多糖,包括:葡萄糖、半乳糖、甘露糖、鼠李糖;
所述蛋白质,包括:精氨酸、赖氨酸、丝氨酸、苏氨酸。
实施例13一种用于治疗痛风的药物
以重量份计,包括以下组分:
海洋藻类糖蛋白1份、葡萄糖醛酸1份、青黛2份;
所述海洋藻类糖蛋白,以重量含量计,包括糖9%,蛋白质88%,
分子量为6kDa;
所述糖为多糖;
所述海洋藻类为:蓝藻;
所述多糖,包括:葡萄糖、半乳糖、甘露糖、鼠李糖;
所述蛋白质,包括:精氨酸、赖氨酸、丝氨酸、苏氨酸。
实施例14一种用于治疗痛风的药物
以重量份计,包括以下组分:
海洋藻类糖蛋白27份、葡萄糖醛酸6份、青黛4份;
所述海洋藻类糖蛋白,以重量含量计,包括糖9%,蛋白质88%,
分子量为20kDa;
所述糖为多糖;
所述海洋藻类为:蓝藻;
所述多糖,包括:葡萄糖、半乳糖、甘露糖、鼠李糖;
所述蛋白质,包括:精氨酸、赖氨酸、丝氨酸、苏氨酸。
实施例15一种用于治疗痛风的药物
以重量份计,包括以下组分:
海洋藻类糖蛋白52份、葡萄糖醛酸14份、青黛5份;
所述海洋藻类糖蛋白,以重量含量计,包括糖30%,蛋白质70%,
分子量为200kDa;
所述糖为多糖;
所述海洋藻类为:蓝藻;
所述多糖,包括:葡萄糖、半乳糖、甘露糖、鼠李糖;
所述蛋白质,包括:精氨酸、赖氨酸、丝氨酸、苏氨酸。
实施例16一种用于治疗痛风的药物
以重量份计,包括以下组分:
海洋藻类糖蛋白99份、葡萄糖醛酸25份、青黛9份;
所述海洋藻类糖蛋白,以重量含量计,包括糖50%,蛋白质50%,
分子量为3000kDa;
所述糖为多糖;
所述海洋藻类为:蓝藻;
所述多糖,包括:葡萄糖、半乳糖、甘露糖、鼠李糖;
所述蛋白质,包括:精氨酸、赖氨酸、丝氨酸、苏氨酸。
上述实施例8-实施例16所述药物在治疗痛风中的应用:
采用实施例7所述的试验方法,本发明组为实施例8-实施例16所述药物,应用效果如下:
(1)本发明药物对链尿佐菌素致大鼠痛风模型的效果
表5本发明药物对链尿佐菌素致大鼠痛风模型的影响
[根据细则26改正13.03.2017] 
Figure WO-DOC-TABLE-5
(2)本发明药物对黄嘌呤致小鼠高尿酸血症模型的治疗效果
表6本发明药物对小鼠高尿酸血症模型血尿酸的影响
Figure PCTCN2017071864-appb-000006
(3)人体临床试验
结果:
痊愈:88例,占88%;
显效:10例,占10%;
无效:2例,占2%;
总有效率:98%;
复发率低,痊愈者6年后的复发率仅为1%。
实施例17一种用于治疗痛风的药物
以重量份计,包括以下组分:
包括海洋藻类糖蛋白1份、青黛8份、牛蕂7份。
所述海洋藻类糖蛋白,以重量含量计,包括糖10%,蛋白质85%,
分子量为16kDa;
所述糖为多糖;
所述海洋藻类为:螺旋藻;
所述多糖,包括:葡萄糖、半乳糖、甘露糖、鼠李糖;
所述蛋白质,包括:精氨酸、赖氨酸、丝氨酸、苏氨酸。
实施例18一种用于治疗痛风的药物
以重量份计,包括以下组分:
包括海洋藻类糖蛋白40份、青黛11份、牛蕂9份。
所述海洋藻类糖蛋白,以重量含量计,包括糖8%,蛋白质88%,
分子量为14kDa;
所述糖为多糖;
所述海洋藻类为:小球藻;
所述多糖,包括:葡萄糖、半乳糖、甘露糖、鼠李糖;
所述蛋白质,包括:精氨酸、赖氨酸、丝氨酸、苏氨酸。
实施例19一种用于治疗痛风的药物
以重量份计,包括以下组分:
包括海洋藻类糖蛋白99份、青黛14份、牛蕂13份。
所述海洋藻类糖蛋白,以重量含量计,包括糖30%,蛋白质70%,
分子量为38kDa;
所述糖为多糖;
所述海洋藻类为:石花菜;
所述多糖,包括:葡萄糖、半乳糖、甘露糖、鼠李糖;
所述蛋白质,包括:精氨酸、赖氨酸、丝氨酸、苏氨酸。
实施例20一种用于治疗痛风的药物
以重量份计,包括以下组分:
包括海洋藻类糖蛋白1份、青黛8份、牛蕂7份、葡萄糖醛酸1份。
所述海洋藻类糖蛋白,以重量含量计,包括糖10%,蛋白质85%,
分子量为16kDa;
所述糖为多糖;
所述海洋藻类为:螺旋藻;
所述多糖,包括:葡萄糖、半乳糖、甘露糖、鼠李糖;
所述蛋白质,包括:精氨酸、赖氨酸、丝氨酸、苏氨酸。
实施例21一种用于治疗痛风的药物
以重量份计,包括以下组分:
包括海洋藻类糖蛋白40份、青黛11份、牛蕂9份、葡萄糖醛酸8份。
所述海洋藻类糖蛋白,以重量含量计,包括糖8%,蛋白质88%,
分子量为14kDa;
所述糖为多糖;
所述海洋藻类为:小球藻;
所述多糖,包括:葡萄糖、半乳糖、甘露糖、鼠李糖;
所述蛋白质,包括:精氨酸、赖氨酸、丝氨酸、苏氨酸。
实施例22一种用于治疗痛风的药物
以重量份计,包括以下组分:
包括海洋藻类糖蛋白99份、青黛14份、牛蕂13份、葡萄糖醛酸15份;
所述海洋藻类糖蛋白,以重量含量计,包括糖30%,蛋白质70%,
分子量为200kDa;
所述糖为多糖;
所述海洋藻类为:石花菜;
所述多糖,包括:葡萄糖、半乳糖、甘露糖、鼠李糖;
所述蛋白质,包括:精氨酸、赖氨酸、丝氨酸、苏氨酸。
上述实施例17-实施例22所述药物在治疗痛风中的应用:
采用实施例7所述的试验方法,本发明组为实施例17-实施例22所述药物,应用效果如下:
(1)本发明药物对链尿佐菌素致大鼠痛风模型的效果
表7本发明药物对链尿佐菌素致大鼠痛风模型的影响
[根据细则26改正13.03.2017] 
Figure WO-DOC-TABLE-7
(2)本发明药物对黄嘌呤致小鼠高尿酸血症模型的治疗效果
表8本发明药物对小鼠高尿酸血症模型血尿酸的影响
Figure PCTCN2017071864-appb-000008
(3)人体临床试验
结果:
痊愈:90例,占90%;
显效:9例,占9%;
无效:1例,占1%;
总有效率:99%;
复发率低,痊愈者5年后无1例复发。
实施例23一种用于治疗痛风的药物
以重量份计,包括以下组分:
海洋藻类糖蛋白80份、苦参10份、木香5份、紫花杜鹃5份、一箭球7份、吴茱萸8份、鹿衔草10份;
所述海洋藻类糖蛋白,以重量含量计,包括糖10%,蛋白质85%,
分子量为15kDa;
所述海洋藻类为:绿藻;
所述糖,以重量份计,包括如下组分:葡萄糖8份,半乳糖5份,甘露糖11份;
所述蛋白质,以重量份,包括如下组分:丝氨酸7份、苏氨酸9份、羟基赖氨酸15份。
实施例24一种用于治疗痛风的药物
以重量份计,包括以下组分:
海洋藻类糖蛋白75份、淫羊藿12份、肉蔻8份、没食子7份、制附子9份、天麻6份、青风藤5份;
所述海洋藻类糖蛋白,以重量含量计,包括糖12%,蛋白质75%,
分子量为8kDa;
所述海洋藻类为:蓝藻;
所述糖,以重量份计,包括如下组分:葡萄糖20份,半乳糖8份,甘露糖15份;
所述蛋白质,以重量份,包括如下组分:丝氨酸10份、苏氨酸15份、羟基赖氨酸17份。
实施例25一种用于治疗痛风的药物
以重量份计,包括以下组分:
海洋藻类糖蛋白70份、附子8份、白扁豆6份、僵蚕5份、半夏3份、苍术7份、独活8份;
所述海洋藻类糖蛋白,以重量含量计,包括糖14%,蛋白质72%,
分子量为20kDa;
所述海洋藻类为:蓝藻;
所述糖,以重量份计,包括如下组分:葡萄糖20份,半乳糖8份,甘露糖15份;
所述蛋白质,以重量份,包括如下组分:丝氨酸10份、苏氨酸15份、羟基赖氨酸17份。
实施例26一种用于治疗痛风的药物
以重量份计,包括以下组分:
海洋藻类糖蛋白78份、川芎10份、泽泻8份、升麻6份、一朵云叶7份、羌活7份、威灵仙5份;
所述海洋藻类糖蛋白,以重量含量计,包括糖22%,蛋白质69%;
分子量为100kDa;
所述海洋藻类为:蓝藻;
所述糖,以重量份计,包括如下组分:葡萄糖20份,半乳糖8份,甘露糖15份;
所述蛋白质,以重量份,包括如下组分:丝氨酸10份、苏氨酸15份、羟基赖氨酸17份。
实施例27一种用于治疗痛风的药物的制备方法
步骤1、称量
按照配方称量海洋藻类糖蛋白和各中药成分;
步骤2、中药的浸提
(1)清洗
将各中药成分,用清水冲洗,去处杂质;
(2)粉碎、微波萃取
将中药粉碎处理成100目药材粉末,加入8倍量50%乙醇,控制温度为60℃,以260W微 波功率、微波波长为130毫米,频率为1200兆赫的微波辐射5min,过滤,收集滤液;分离药渣,加入6倍体积的清水,控制温度为50℃,以200W微波功率、微波波长为140毫米,频率为1250兆赫的微波辐射5min,过滤,收集滤液;
合并两次的滤液,喷雾干燥,得中药粉末;
步骤3、加入海洋藻类糖蛋白
海洋藻类糖蛋白粉末,和上述制好的中药粉末合并,进行混合,制成胶囊、片剂等制剂。
上述实施例23-实施例26所述药物在治疗痛风中的应用:
采用实施例7所述的试验方法,本发明组为实施例23-实施例26所述药物,应用效果如下:
(1)本发明药物对链尿佐菌素致大鼠痛风模型的效果
表9本发明药物对链尿佐菌素致大鼠痛风模型的影响
[根据细则26改正13.03.2017] 
Figure WO-DOC-TABLE-9
(2)本发明药物对黄嘌呤致小鼠高尿酸血症模型的治疗效果
表10本发明药物对小鼠高尿酸血症模型血尿酸的影响
Figure PCTCN2017071864-appb-000010
(3)人体临床试验
结果:
痊愈:90例,占90%;
显效:9例,占9%;
无效:1例,占1%;
总有效率:99%;
复发率低,痊愈者5年后无1例复发。
本发明所述药物,pH为5.3-9.8之间,优选为6.5-7.5之间。
本发明经过大量试验,我们采取了海洋贝壳类、畜禽类的骨头、海洋动物的骨架中提取的糖蛋白及多糖、蛋白的混合物进行多次试验,也能实现本发明的发明目的。
实施例28一种用于治疗痛风的药物
所述药物,为多糖、蛋白质的混合物;
所述药物,以重量份计,包括多糖1-99%、蛋白质1-99%;
所述多糖,包括:葡萄糖、半乳糖、甘露糖、鼠李糖;
所述蛋白质,包括:精氨酸、赖氨酸、丝氨酸、苏氨酸;
所述多糖和蛋白质的混合物,多糖的分子量为0.2-3000kDa,蛋白质的分子量为0.2-3000kDa。
所述多糖和蛋白的混合物,进一步为藻类多糖和藻类蛋白的混合物;
所述藻类多糖和藻类蛋白的混合物,还包括色素;
所述色素为藻类物质中含有的天然色素;
所述藻类蛋白可以是藻蓝蛋白、藻红蛋白或藻黄色蛋白。
所述糖蛋白包括合成糖蛋白及合成多糖、蛋白。
本发明所述药物对犬经口给药12周无毒性反应剂量为1.6g/kg,相当于人用等效剂量的50倍,故可认为临床试验的安全性可以得到保障。
本发明所述药物,还可以是保健品或食品。
以上显示和描述了本发明的基本原理和主要特征和本发明的优点。本行业的技术人员应该了解,本发明不受上述实施例的限制,上述实施例和说明书中描述的只是说明本发明的原理,在不脱离本发明精神和范围的前提下,本发明还会有各种变化和改进,这些变化和改进都落入要求保护的本发明范围内。本发明要求保护范围由所附的权利要求书及其等效物界定。

Claims (10)

  1. 一种用于治疗痛风的药物,其特征在于:所述药物为糖蛋白或多糖和蛋白质的混合物或多肽或蛋白。
  2. 根据权利要求1所述的一种用于治疗痛风的药物,其特征在于:所述药物为海洋藻类糖蛋白。
  3. 根据权利要求2所述的一种用于治疗痛风的药物,其特征在于:所述糖蛋白,以重量含量计,包括糖1-99%,蛋白质1-99%;所述海洋藻类糖蛋白,以重量含量计,包括糖1-99%,蛋白质1-99%;所述多糖和蛋白质的混合物,以重量含量计,包括糖1-99%,蛋白质1-99%。
  4. 根据权利要求2所述的一种用于治疗痛风的药物,其特征在于:所述糖蛋白,分子量为0.2-3000kDa;所述海洋藻类糖蛋白,分子量为0.2-3000kDa;所述多糖和蛋白质的混合物,多糖的分子量为0.2-3000kDa,蛋白质的分子量为0.2-3000kDa。
  5. 根据权利要求1所述的一种用于治疗痛风的药物,其特征在于:以重量含量计,包括所述糖蛋白1-99份、葡萄糖醛酸1-25份。
  6. 根据权利要求1所述的一种用于治疗痛风的药物,其特征在于:以重量含量计,包括糖蛋白1-99份、葡萄糖醛酸1-25份、青黛2-9份。
  7. 根据权利要求2所述的一种用于治疗痛风的药物,其特征在于:所述藻类为蓝藻、绿藻、红藻、金藻、褐藻中的一种或多种。
  8. 根据权利要求1所述的一种用于治疗痛风的药物,其特征在于:以重量含量计,包括糖蛋白1-99份、青黛8-14份、牛蕂7-13份。
  9. 根据权利要求1所述的一种用于治疗痛风的药物,其特征在于:以重量含量计,包括糖蛋白1-99份、青黛8-14份、牛蕂7-13份、葡萄糖醛酸1-15份。
  10. 根据权利要求5-9任一项所述的一种用于治疗痛风的药物,其特征在于:所述糖蛋白、海洋藻类糖蛋白,以重量含量计,包括糖1-99%,蛋白质1-99%。
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