WO2017129047A1 - Drug for treating rheumatism and rheumatoid diseases - Google Patents

Drug for treating rheumatism and rheumatoid diseases Download PDF

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Publication number
WO2017129047A1
WO2017129047A1 PCT/CN2017/071804 CN2017071804W WO2017129047A1 WO 2017129047 A1 WO2017129047 A1 WO 2017129047A1 CN 2017071804 W CN2017071804 W CN 2017071804W WO 2017129047 A1 WO2017129047 A1 WO 2017129047A1
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Prior art keywords
parts
rheumatoid
glycoprotein
weight
protein
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PCT/CN2017/071804
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French (fr)
Chinese (zh)
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程龙
徐宝贞
程潜
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程龙
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Publication of WO2017129047A1 publication Critical patent/WO2017129047A1/en

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    • 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
    • A61K31/7088Compounds having three or more nucleosides or nucleotides
    • A61K31/7105Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
    • 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)
    • 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)
    • A61K36/31Brassicaceae 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
    • A61K36/484Glycyrrhiza (licorice)
    • 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)
    • A61K36/63Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
    • A61K36/634Forsythia
    • 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)
    • A61K36/66Papaveraceae (Poppy family), e.g. bloodroot
    • 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

Definitions

  • the invention relates to a medicine for treating rheumatoid rheumatoid, belonging to the technical field of medicine.
  • Rheumatism and rheumatoid disease are "stubborn”, “difficult”, and “annoying”. They are cured for a long time, and they cause repeated suffering, which makes patients suffer and headaches. According to the World Center for Disease Control, rheumatism and rheumatoid disease are another intractable disease that threatens human health after cancer. Currently, in the United States, Europe and Japan, the number of patients with rheumatism and rheumatoid disease is nearly 300 million. According to a survey in some parts of China, 85% of people over the age of 45 have different degrees of suffering from this disease, and the medical expenses paid are hundreds of millions of dollars, and there is a trend of further increase.
  • Rheumatism and rheumatoid arthritis Chinese medicine believes that the disease caused by the combination of wind and wet. Symptoms include headache, fever, slight sweat, bad wind, weight, dysuria, sore throat, and inability to flex and stretch. In addition to pain, joint lesions are accompanied by swelling and movement disorders, showing a chronic course of attack and remission. Because the patient's blood circulation is not smooth, the nutrients required by the muscles or tissues cannot be transported through the blood circulation, resulting in the lack of nutrition of the patient's muscles and accelerated aging and becoming stiff. However, the muscles and blood vessels of the patients will shrink, and some patients may appear. Joint disability and visceral failure. According to relevant experts, 50% of rheumatoid and rheumatoid patients have paralysis throughout the year.
  • CN200610151223.3 discloses a traditional Chinese medicine for treating tuberculosis, characterized in that the pharmaceutically active ingredient of the traditional Chinese medicine for treating tuberculosis is from 45 to 55 parts of almond, 90 to 110 parts, 90 to 110 parts, 90 to 90 parts by weight.
  • the present invention provides a medicine for treating rheumatoid rheumatoid to achieve the following objects:
  • the drug of the invention can effectively alleviate the joint pain of rheumatoid arthritis in rats, and the threshold of joint pain is significantly increased;
  • the drug of the present invention has a significant alleviating effect on joint swelling of rat rheumatoid arthritis
  • the drug of the invention can increase the content of L-ENK and ⁇ -END in the hypothalamus of rats and reduce the pro-inflammatory factors IL-1 ⁇ and IL-6.
  • the secretion inhibits the synthesis and secretion of serum immunoglobulin IgG and inhibits the release of the pain stimulating factor SP.
  • the present invention adopts the following technical solutions:
  • a medicament for treating rheumatoid rheumatoid characterized in that the medicament is a glycoprotein, or a mixture or polypeptide or protein of polysaccharide and protein, the glycoprotein comprising sugar 1-99%, protein 1-99%;
  • the mixture of polysaccharide and protein, by weight, comprises 1-99% polysaccharide, 1-99% 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 by weight, includes 1-99 parts of marine algae glycoprotein and 1-28 parts of glucuronic acid.
  • the drug comprises, by weight, 1-99 parts of marine algae glycoprotein, 1-23 parts of glucuronic acid, and 3-11 parts of medlar.
  • the algae is one or more of cyanobacteria, green algae, red algae, gold algae, and brown algae.
  • the drug by weight, includes 1-99 parts of marine algae glycoprotein, 5-13 parts of medlar, 6-14 parts of moxibustion licorice, and 1-17 parts of glucuronic acid.
  • the drug by weight, includes 1-99 parts of marine algae glycoprotein, 5-13 parts of medlar, 6-14 parts of moxibustion licorice, 7-12 parts of Corydalis, and 5-10 parts of Forsythia.
  • 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 drug of the present invention can effectively alleviate the joint pain of rheumatoid arthritis in rats, and the threshold of joint pain is significantly increased.
  • the threshold value of joint pain is 1147-1186 g
  • the threshold value of joint pain is 870.6. -945.7g
  • the drug of the present invention has a significant alleviating effect on joint swelling of rat rheumatoid arthritis.
  • the swelling index of the right joint of the animal of the present invention was significantly decreased, being 300.3-330.5 m/kg; on the 30th day of the experiment, The right joint swelling index of animals is 231.8-270.5m/kg;
  • the drug of the invention can increase the content of L-ENK and ⁇ -END in the hypothalamus of rats, reduce the secretion of pro-inflammatory factors IL-1 ⁇ and IL-6, inhibit the synthesis and secretion of serum immunoglobulin IgG, and inhibit the pain-stimulating factor.
  • SP release, L-ENK content It is 170.1-212.6pg/g
  • the ⁇ -END content is 135.6-170.6pg/g
  • the SP content is 60.3-67.5ng/L
  • the IgG content is 12.00-12.58g/L
  • the IL-1 ⁇ content is 0.200-0.231mg/ L
  • IL-6 content is 40.15-45.56 ng / L.
  • Embodiment 1 A medicine for treating rheumatoid rheumatoid
  • the drug is a marine algae glycoprotein
  • the marine algae glycoprotein which comprises 1% by weight of sugar and 99% by weight,
  • the molecular weight is 0.2 kDa
  • the marine algae is: cyanobacteria
  • the sugar is a polysaccharide
  • the polysaccharide comprises: glucose, mannose, rhamnose, galactose;
  • the protein includes: aspartic acid, glutamic acid, glycine, arginine, lysine, serine, threonine.
  • Example 2 A medicament for treating rheumatoid rheumatoid
  • the drug is a marine algae glycoprotein
  • the marine algae glycoprotein which comprises 10% by weight of sugar and 80% by weight of protein
  • the molecular weight is 13kDa
  • the marine algae is: green algae;
  • the sugar is a polysaccharide
  • the polysaccharide comprises: glucose, mannose, rhamnose, galactose;
  • the protein includes: aspartic acid, glutamic acid, glycine, arginine, lysine, serine, threonine.
  • Example 3 A medicament for treating rheumatoid rheumatoid
  • the drug is a marine algae glycoprotein
  • the marine algae glycoprotein comprising 20% sugar, 72% protein, by weight
  • the molecular weight is 5kDa
  • the marine algae is: cyanobacteria
  • the sugar is a polysaccharide
  • the polysaccharide comprises: glucose, mannose, rhamnose, galactose;
  • the protein includes: aspartic acid, glutamic acid, glycine, arginine, lysine, serine, threonine.
  • Embodiment 4 A medicine for treating rheumatoid rheumatoid
  • the drug is a marine algae glycoprotein
  • the marine algae glycoprotein comprises, by weight, 35% sugar, 58% protein,
  • the molecular weight is 120kDa
  • the marine algae is: red algae;
  • the sugar is a polysaccharide
  • the polysaccharide comprises: glucose, mannose, rhamnose, galactose;
  • the protein includes: aspartic acid, glutamic acid, glycine, arginine, lysine, serine, threonine.
  • Embodiment 5 A medicine for treating rheumatoid rheumatoid
  • the drug is a marine algae glycoprotein
  • the marine algal glycoprotein which comprises 60% by weight of sugar and 32% by weight,
  • the molecular weight is 400kDa;
  • the marine algae is: brown algae;
  • the sugar is a polysaccharide
  • the polysaccharide comprises: glucose, mannose, rhamnose, galactose;
  • the protein includes: aspartic acid, glutamic acid, glycine, arginine, lysine, serine, threonine.
  • Embodiment 6 A medicine for treating rheumatoid rheumatoid
  • the drug is a marine algae glycoprotein
  • the marine algae glycoprotein by weight, comprises 99% sugar, 1% protein,
  • the molecular weight is 3000kDa
  • the marine algae is: gold algae;
  • the sugar is a polysaccharide
  • the polysaccharide comprises: glucose, mannose, rhamnose, galactose;
  • the protein includes: aspartic acid, glutamic acid, glycine, arginine, lysine, serine, threonine.
  • the glycoprotein described in the above Examples 1-6 further includes 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 drug is a synthetic glycoprotein and a synthetic polysaccharide and protein.
  • 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.
  • Example 7 Application test of a medicament for treating rheumatoid rheumatoid
  • the model rats were randomly divided into two groups: a blank control group, a model control group, and the present invention group 1-6.
  • the modeling method was as follows: the rats were placed in 6 ° C cold water, the water depth was 2 cm, standing for 20 minutes, and the electric fan was blown 3 Wind speed, once a day for 14 consecutive days; on the first day of modeling, each model rat was injected with 0-1 ml of complete Freund's adjuvant once in the right hind paw, and after 19 days, the invention group 1-6
  • the medicaments according to Examples 1-6 of the present invention were respectively administered at a dose of 3 g/day, 3 times a day for 6 consecutive days.
  • the model control group and the blank control group were intragastrically administered with normal saline.
  • the thalamus, plasma, serum were separated, and the method of kit was used to determine the content of L-ENK and ⁇ -END in the hypothalamus, plasma SP content, serum immunoglobulin IgG content, serum cytokine IL- 1 ⁇ content, IL-6 content.
  • Example 1 1152 ⁇ 85.4 870.6 ⁇ 73.3
  • Example 2 1162 ⁇ 86.4 915.9 ⁇ 72.5
  • Example 3 1186 ⁇ 75.4 945.7 ⁇ 85.4
  • Example 4 1160 ⁇ 79.1 923.8 ⁇ 76.0
  • Example 5 1158 ⁇ 69.7 912.4 ⁇ 79.2
  • Example 6 1147 ⁇ 70.2 870.6 ⁇ 84.6
  • the medicine of the invention can effectively relieve joint pain of rheumatoid arthritis in rats, and the threshold of joint pain is significantly increased.
  • the joint pain threshold is 1147-1186g, and the joint pain threshold is 870.6-945.7g on the 30th day of the experiment. ;
  • the medicine of the invention has obvious remission effect on joint swelling of rat rheumatoid arthritis.
  • the swelling index of the right joint of the animal of the invention group is significantly reduced, which is 300.3-330.5 m/kg; on the 30th day of the experiment, the right joint of the animal The swelling index is 231.8-270.5 m/kg.
  • the medicine of the invention can increase the content of L-ENK and ⁇ -END in the hypothalamus of rats, both of which have analgesic effect, reduce the secretion of pro-inflammatory factors IL-1 ⁇ and IL-6, and inhibit the synthesis and secretion of serum immunoglobulin IgG.
  • the L-ENK content is 170.1-212.6pg/g
  • the ⁇ -END content is 135.6-170.6pg/g
  • the SP content is 60.3-67.5ng/L
  • the IgG content is 12.00-12.58g. /L
  • IL-1 ⁇ The content is 0.200-0.231 mg/L
  • the IL-6 content is 40.15-45.56 ng/L.
  • Embodiment 8 A medicine for treating rheumatoid rheumatoid
  • the marine algae glycoprotein which comprises 9% sugar and 80% protein by weight
  • the molecular weight is 8kDa
  • the marine algae is: chlorella;
  • the sugar is a polysaccharide
  • the polysaccharide comprises: glucose, mannose, rhamnose, galactose;
  • the protein includes: aspartic acid, glutamic acid, glycine, arginine, lysine, serine, threonine.
  • Embodiment 9 A medicine for treating rheumatoid rheumatoid
  • the drug includes 24 parts of marine algae glycoprotein and 8 parts of glucuronic acid.
  • Embodiment 10 A medicament for treating rheumatoid rheumatoid
  • the drug includes 57 parts of marine algae glycoprotein and 16 parts of glucuronic acid.
  • Embodiment 11 A medicament for treating rheumatoid rheumatoid
  • the drug includes 99 parts of marine algae glycoprotein and 28 parts of glucuronic acid.
  • Embodiment 12 A medicament for treating rheumatoid rheumatoid
  • the marine algae glycoprotein which comprises, by weight, 16% sugar, 80% protein,
  • the molecular weight is 12kDa
  • the marine algae is: spirulina
  • the sugar is a polysaccharide
  • the polysaccharide comprises: glucose, mannose, rhamnose, galactose;
  • the protein includes: aspartic acid, glutamic acid, glycine, arginine, lysine, serine, threonine.
  • Embodiment 13 A medicament for treating rheumatoid rheumatoid
  • the drug includes 34 parts of marine algae glycoprotein, 8 parts of glucuronic acid, and 5 parts of barley in parts by weight.
  • Embodiment 14 A medicament for treating rheumatoid rheumatoid
  • the drug includes 59 parts of marine algae glycoprotein, 18 parts of glucuronic acid, and 8 parts of barley in parts by weight.
  • Embodiment 15 A medicament for treating rheumatoid rheumatoid
  • the drug includes 99 parts of marine algae glycoprotein, 23 parts of glucuronic acid, and 11 parts of barley in parts by weight.
  • Example 7 Using the test method described in Example 7, the modification was carried out by using the drugs described in Example 8 - Example 15, and the application effects were as follows:
  • Example 10 is the most preferred embodiment
  • Example 12-15 only changed the weight ratio of marine algae glycoprotein, glucuronic acid, and strontium. From the experimental results, Example 14 is the most preferred embodiment
  • Embodiment 16 A medicament for treating rheumatoid rheumatoid
  • weight content it includes 1 part of marine algae glycoprotein, 5 parts of green barley, 6 parts of moxibustion licorice, and 1 part of glucuronic acid.
  • the marine algae glycoprotein including 30% sugar, 50% protein, by weight
  • the molecular weight is 20kDa;
  • the marine algae is: long-leaved laver;
  • the sugar is a polysaccharide
  • the polysaccharide comprises: glucose, mannose, rhamnose, galactose;
  • the protein includes: aspartic acid, glutamic acid, glycine, arginine, lysine, serine, threonine.
  • Embodiment 17 A medicament for treating rheumatoid rheumatoid
  • Embodiment 18 A medicament for treating rheumatoid rheumatoid
  • Embodiment 19 A medicament for treating rheumatoid rheumatoid
  • marine algae glycoprotein In parts by weight, including 1 part of marine algae glycoprotein, 5 parts of green barley, 6 parts of moxibustion licorice, 7 parts of Corydalis, and 5 parts of Forsythia.
  • the marine algae glycoprotein which comprises 50% by weight of sugar and 20% by weight of protein,
  • the molecular weight is 200kDa
  • the marine algae is: Sargassum;
  • the sugar is a polysaccharide
  • the polysaccharide comprises: glucose, mannose, rhamnose, galactose;
  • the protein includes: aspartic acid, glutamic acid, glycine, arginine, lysine, serine, threonine.
  • Embodiment 20 A medicament for treating rheumatoid rheumatoid
  • Embodiment 21 A medicament for treating rheumatoid rheumatoid
  • Example 7 The test method described in Example 7 was adopted, and the modification was carried out by using the drugs described in Example 16 to Example 21, and the application effects were as follows:
  • Example 16-18 only the weight ratio of marine algae glycoprotein, barley, moxibustion, and glucuronic acid was changed. From the experimental results, Example 17 is the most preferred embodiment
  • Example 19-21 only the weight ratio of marine algae glycoprotein, barley, moxibustion licorice, Corydalis, and forsythia was changed. From the experimental results, Example 20 is the most preferred embodiment.
  • Embodiment 22 A medicament for treating rheumatoid rheumatoid
  • the marine algae glycoprotein which comprises 8% sugar and 80% protein by weight
  • the molecular weight is 10kDa
  • the marine algae is: chlorella;
  • the sugar in parts by weight, comprises the following components: 55 parts of glucose, 20 parts of mannose, 13 parts of rhamnose, and 8 parts of galactose;
  • the protein in parts by weight, includes the following components: 13 parts of aspartic acid, 11 parts of glutamic acid, and 8 parts of glycine.
  • the joint pain threshold was 1450g, and the joint pain threshold was 1125g on the 30th day of the experiment;
  • the swelling index of the right joint of the animals of the present invention was significantly decreased to 212.3 m/kg; on the 30th day of the experiment, the index of swelling of the right joint of the animals was 185.6 m/kg.
  • the L-ENK content was 289.6 pg/g
  • the ⁇ -END content was 382.3 pg/g
  • the SP content was 50.3 ng/L
  • the IgG content was 9.65 g/L
  • the IL-1 ⁇ content was 0.135 mg/L
  • the IL-6 content was It is 23.56 ng/L.
  • Example 23 A method for preparing a medicament for treating rheumatoid rheumatoid arthritis:
  • Step 1 weighing
  • the traditional Chinese medicine is pulverized into 100 mesh medicinal material powder, 10 times of 50% ethanol is added, the temperature is controlled to 60 ° C, microwave irradiation with 260 W microwave power, microwave wavelength of 130 mm, frequency of 1200 MHz for 5 min, filtration, and the filtrate is collected;
  • the filtrates were combined twice; filtered through a 0.45 ⁇ m microporous membrane to obtain a filtrate.
  • the obtained filtrate was introduced into a double flow spiral nozzle of a Büchi290 small spray dryer via a peristaltic pump, and the inlet temperature was controlled at 125 ° C, and the feed rate was 3 mL / Min, spray drying to obtain a traditional Chinese medicine powder.
  • the marine algae glycoprotein powder and the above traditional Chinese medicine powder are uniformly mixed to prepare different dosage forms such as capsules and tablets.
  • 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 24 A medicament for treating rheumatoid rheumatoid
  • 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, mannose, rhamnose, galactose;
  • the protein comprises: asparagine, cysteine, lysine, arginine, serine, threonine, alanine, aspartic acid, glutamine, glutamic acid, histidine, Isoleucine, glycine, leucine, methionine, phenylalanine, valine, tyrosine, valine.
  • 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

The present invention provides a drug for treating rheumatism and rheumatoid diseases. The drug is glycoprotein, or a mixture of polysaccharide and protein, or polypeptide or protein.

Description

一种用于治疗风湿类风湿的药物A medicine for treating rheumatoid rheumatoid 技术领域Technical field
本发明涉及一种用于治疗风湿类风湿的药物,属于医药技术领域。The invention relates to a medicine for treating rheumatoid rheumatoid, belonging to the technical field of medicine.
背景技术Background technique
风湿、类风湿病“顽”、“难”、“烦”,久治不愈,反复发作,使患者受苦,令医生头痛。据世界疾病控制中心报道:风湿、类风湿病是继癌症之后又一种严重威胁人类健康的疑难杂症,目前在美国、欧洲和日本,风湿、类风湿病患者人群高达近3亿人。在我国部分地区的一项调查表明,45岁以上年龄组中,有85%的人不同程度的患有此病,由此支付的医疗费用高达数亿元,而且还有进一步增加的趋势。若延误治疗,会直接威胁心脏,部分患者会出现关节致残和内脏功能衰竭。风湿和类风湿性关节炎,中医认为是风和湿两种病邪结合所致的病症。症见有头痛、发热、微汗、恶风、身重、小便不利、骨节酸痛、不能屈伸等。关节病变除有疼痛外尚伴有肿胀和活动障碍,呈发作与缓解交替的慢性病程。由于患者的血液循环不通畅,导致肌肉或者组织所需要的营养无法通过血液循环来输送,致使患者肌肉缺少营养而加速老化变得僵硬,严重的会导致患者肌肉和血管萎缩,部分患者且可出现关节致残和内脏功能衰竭。据有关专家估计,全年有50%的风湿、类风湿患者出现瘫痪。Rheumatism and rheumatoid disease are "stubborn", "difficult", and "annoying". They are cured for a long time, and they cause repeated suffering, which makes patients suffer and headaches. According to the World Center for Disease Control, rheumatism and rheumatoid disease are another intractable disease that threatens human health after cancer. Currently, in the United States, Europe and Japan, the number of patients with rheumatism and rheumatoid disease is nearly 300 million. According to a survey in some parts of China, 85% of people over the age of 45 have different degrees of suffering from this disease, and the medical expenses paid are hundreds of millions of dollars, and there is a trend of further increase. If the treatment is delayed, it will directly threaten the heart, and some patients will have joint disability and visceral failure. Rheumatism and rheumatoid arthritis, Chinese medicine believes that the disease caused by the combination of wind and wet. Symptoms include headache, fever, slight sweat, bad wind, weight, dysuria, sore throat, and inability to flex and stretch. In addition to pain, joint lesions are accompanied by swelling and movement disorders, showing a chronic course of attack and remission. Because the patient's blood circulation is not smooth, the nutrients required by the muscles or tissues cannot be transported through the blood circulation, resulting in the lack of nutrition of the patient's muscles and accelerated aging and becoming stiff. Seriously, the muscles and blood vessels of the patients will shrink, and some patients may appear. Joint disability and visceral failure. According to relevant experts, 50% of rheumatoid and rheumatoid patients have paralysis throughout the year.
西药治疗见效快,但治标不治本,停药即复发,副作用极大,易造成终生疾病和并发症,如损伤神经系统,肝肾等内脏器官,造成内分泌失调,胃出血等症,现有中药疗效单一,显效慢,治愈率低,疗程长等弊端。因此,迫切需要有效治疗风湿、类风湿疾病的药物。Western medicine treatment is effective, but the symptoms are not cured, the drug is relapsed, the side effects are extremely large, and it is easy to cause lifelong diseases and complications, such as damage to the nervous system, liver and kidney and other internal organs, causing endocrine disorders, stomach bleeding and other diseases, existing Chinese medicine The curative effect is single, the effect is slow, the cure rate is low, and the course of treatment is long. Therefore, there is an urgent need for drugs that effectively treat rheumatism and rheumatoid diseases.
CN200610151223.3公开了一种治疗肺结核的中药,其特征在于治疗肺结核的中药的药物活性成分按重量份数比由45~55份杏仁、90~110份百部、90~110份茯苓、90~110份薏米、90~110份当归、45~55份五味子、90~110份枸杞、45~55黄精、90~110份百合、90~110份白及、90~110份白果、45~55份三七、45~55份川贝、45~55份蛤蚧、380~420份黄瓜子和380~420份菠菜籽制成。CN200610151223.3 discloses a traditional Chinese medicine for treating tuberculosis, characterized in that the pharmaceutically active ingredient of the traditional Chinese medicine for treating tuberculosis is from 45 to 55 parts of almond, 90 to 110 parts, 90 to 110 parts, 90 to 90 parts by weight. 110 parts of glutinous rice, 90-110 parts of angelica, 45-55 parts of schisandra, 90-110 parts of medlar, 45-55 yellow essence, 90-110 parts of lily, 90-110 parts of white and 90-110 parts of ginkgo, 45-55 parts 37, 45 to 55, Chuanbei, 45 to 55 parts of glutinous rice, 380 to 420 parts of cucumber seeds and 380 to 420 parts of spinach seeds.
发明内容Summary of the invention
本发明为解决现有技术中存在的不足,提供一种用于治疗风湿类风湿的药物,以实现以下发明目的:In order to solve the deficiencies in the prior art, the present invention provides a medicine for treating rheumatoid rheumatoid to achieve the following objects:
(1)本发明药物能有效缓解大鼠类风湿性关节炎的关节疼痛,关节痛阈值显著升高;(1) The drug of the invention can effectively alleviate the joint pain of rheumatoid arthritis in rats, and the threshold of joint pain is significantly increased;
(2)本发明药物对大鼠类风湿性关节炎关节肿胀有明显缓解作用;(2) The drug of the present invention has a significant alleviating effect on joint swelling of rat rheumatoid arthritis;
(3)本发明药物能提高大鼠下丘脑L-ENK、β-END含量,降低促炎症因子IL-1β、IL-6 的分泌,抑制血清免疫球蛋白IgG的合成和分泌,抑制痛兴奋因子SP的释放。(3) The drug of the invention can increase the content of L-ENK and β-END in the hypothalamus of rats and reduce the pro-inflammatory factors IL-1β and IL-6. The secretion inhibits the synthesis and secretion of serum immunoglobulin IgG and inhibits the release of the pain stimulating factor SP.
为解决以上技术问题,本发明采用如下技术方案:In order to solve the above technical problems, the present invention adopts the following technical solutions:
一种用于治疗风湿类风湿的药物,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;A medicament for treating rheumatoid rheumatoid, characterized in that the medicament is a glycoprotein, or a mixture or polypeptide or protein of polysaccharide and protein, the glycoprotein comprising sugar 1-99%, protein 1-99%; The mixture of polysaccharide and protein, by weight, comprises 1-99% polysaccharide, 1-99% protein. The glycoprotein has a molecular weight of 0.2-3000 kDa;
以下是对上述技术方案的进一步改进:The following are further improvements to the above technical solutions:
所述药物为海洋藻类糖蛋白。The drug is a marine algae glycoprotein.
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%。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%.
所述海洋藻类糖蛋白,分子量为0.2-3000kDa;The marine algae glycoprotein has a molecular weight of 0.2-3000 kDa;
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。The polysaccharide and protein mixture, the polysaccharide has a molecular weight of 0.2-3000 kDa, and the protein has a molecular weight of 0.2-3000 kDa.
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。The drug comprises, by weight, 1-99 parts of glycoprotein and 1-25 parts of glucuronic acid.
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1-28份。The drug, by weight, includes 1-99 parts of marine algae glycoprotein and 1-28 parts of glucuronic acid.
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1-23份、青黛3-11份。The drug comprises, by weight, 1-99 parts of marine algae glycoprotein, 1-23 parts of glucuronic acid, and 3-11 parts of medlar.
所述藻类为蓝藻、绿藻、红藻、金藻、褐藻中的一种或多种。The algae is one or more of cyanobacteria, green algae, red algae, gold algae, and brown algae.
所述药物,以重量含量计,包括海洋藻类糖蛋白1-99份、青黛5-13份、灸甘草6-14份、葡萄糖醛酸1-17份。The drug, by weight, includes 1-99 parts of marine algae glycoprotein, 5-13 parts of medlar, 6-14 parts of moxibustion licorice, and 1-17 parts of glucuronic acid.
所述药物,以重量含量计,包括海洋藻类糖蛋白1-99份、青黛5-13份、灸甘草6-14份、延胡索7-12份、连翘5-10份。The drug, by weight, includes 1-99 parts of marine algae glycoprotein, 5-13 parts of medlar, 6-14 parts of moxibustion licorice, 7-12 parts of Corydalis, and 5-10 parts of Forsythia.
所述药物,以重量含量计,包括糖1-99%,蛋白质1-99%。The drug, by weight, includes 1-99% sugar and 1-99% protein.
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%。The marine algae glycoprotein comprises, by weight, 1-99% sugar and 1-99% protein.
相对现有技术,本发明的有益效果为:Compared with the prior art, the beneficial effects of the present invention are:
(1)本发明药物能有效缓解大鼠类风湿性关节炎的关节疼痛,关节痛阈值显著升高,试验第25天,关节痛阈值为1147-1186g,试验第30天,关节痛阈值为870.6-945.7g;(1) The drug of the present invention can effectively alleviate the joint pain of rheumatoid arthritis in rats, and the threshold of joint pain is significantly increased. On the 25th day of the experiment, the threshold value of joint pain is 1147-1186 g, and the 30th day of the experiment, the threshold value of joint pain is 870.6. -945.7g;
(2)本发明药物对大鼠类风湿性关节炎关节肿胀有明显缓解作用,试验第25天,本发明组动物右关节肿胀指数显著降低,为300.3-330.5m/kg;试验第30天,动物右关节肿胀指数为231.8-270.5m/kg;(2) The drug of the present invention has a significant alleviating effect on joint swelling of rat rheumatoid arthritis. On the 25th day of the experiment, the swelling index of the right joint of the animal of the present invention was significantly decreased, being 300.3-330.5 m/kg; on the 30th day of the experiment, The right joint swelling index of animals is 231.8-270.5m/kg;
(3)本发明药物能提高大鼠下丘脑L-ENK、β-END含量,降低促炎症因子IL-1β、IL-6的分泌,抑制血清免疫球蛋白IgG的合成和分泌,抑制痛兴奋因子SP的释放,L-ENK含量 为170.1-212.6pg/g,β-END含量为135.6-170.6pg/g,SP含量为60.3-67.5ng/L,IgG含量为12.00-12.58g/L,IL-1β含量为0.200-0.231mg/L,IL-6含量为40.15-45.56ng/L。(3) The drug of the invention can increase the content of L-ENK and β-END in the hypothalamus of rats, reduce the secretion of pro-inflammatory factors IL-1β and IL-6, inhibit the synthesis and secretion of serum immunoglobulin IgG, and inhibit the pain-stimulating factor. SP release, L-ENK content It is 170.1-212.6pg/g, the β-END content is 135.6-170.6pg/g, the SP content is 60.3-67.5ng/L, the IgG content is 12.00-12.58g/L, and the IL-1β content is 0.200-0.231mg/ L, IL-6 content is 40.15-45.56 ng / L.
具体实施方式detailed description
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。The preferred embodiments of the present invention are described in the following, and the preferred embodiments described herein are intended to illustrate and explain the invention.
实施例1一种用于治疗风湿类风湿的药物Embodiment 1 A medicine for treating rheumatoid rheumatoid
所述药物为海洋藻类糖蛋白;The drug is a marine algae glycoprotein;
所述海洋藻类糖蛋白,以重量含量计,包括糖1%,蛋白质99%,The marine algae glycoprotein, which comprises 1% by weight of sugar and 99% by weight,
分子量为0.2kDa;The molecular weight is 0.2 kDa;
所述海洋藻类为:蓝藻;The marine algae is: cyanobacteria;
所述糖为多糖;The sugar is a polysaccharide;
所述多糖,包括:葡萄糖、甘露糖、鼠李糖、半乳糖;The polysaccharide comprises: glucose, mannose, rhamnose, galactose;
所述蛋白质,包括:天冬氨酸、谷氨酸、甘氨酸、精氨酸、赖氨酸、丝氨酸、苏氨酸。The protein includes: aspartic acid, glutamic acid, glycine, arginine, lysine, serine, threonine.
实施例2一种用于治疗风湿类风湿的药物Example 2 A medicament for treating rheumatoid rheumatoid
所述药物为海洋藻类糖蛋白;The drug is a marine algae glycoprotein;
所述海洋藻类糖蛋白,以重量含量计,包括糖10%,蛋白质80%,The marine algae glycoprotein, which comprises 10% by weight of sugar and 80% by weight of protein,
分子量为13kDa;The molecular weight is 13kDa;
所述海洋藻类为:绿藻;The marine algae is: green algae;
所述糖为多糖;The sugar is a polysaccharide;
所述多糖,包括:葡萄糖、甘露糖、鼠李糖、半乳糖;The polysaccharide comprises: glucose, mannose, rhamnose, galactose;
所述蛋白质,包括:天冬氨酸、谷氨酸、甘氨酸、精氨酸、赖氨酸、丝氨酸、苏氨酸。The protein includes: aspartic acid, glutamic acid, glycine, arginine, lysine, serine, threonine.
实施例3一种用于治疗风湿类风湿的药物Example 3 A medicament for treating rheumatoid rheumatoid
所述药物为海洋藻类糖蛋白;The drug is a marine algae glycoprotein;
所述海洋藻类糖蛋白,以重量含量计,包括糖20%,蛋白质72%,The marine algae glycoprotein, comprising 20% sugar, 72% protein, by weight
分子量为5kDa;The molecular weight is 5kDa;
所述海洋藻类为:蓝藻;The marine algae is: cyanobacteria;
所述糖为多糖;The sugar is a polysaccharide;
所述多糖,包括:葡萄糖、甘露糖、鼠李糖、半乳糖;The polysaccharide comprises: glucose, mannose, rhamnose, galactose;
所述蛋白质,包括:天冬氨酸、谷氨酸、甘氨酸、精氨酸、赖氨酸、丝氨酸、苏氨酸。The protein includes: aspartic acid, glutamic acid, glycine, arginine, lysine, serine, threonine.
实施例4一种用于治疗风湿类风湿的药物 Embodiment 4 A medicine for treating rheumatoid rheumatoid
所述药物为海洋藻类糖蛋白;The drug is a marine algae glycoprotein;
所述海洋藻类糖蛋白,以重量含量计,包括糖35%,蛋白质58%,The marine algae glycoprotein comprises, by weight, 35% sugar, 58% protein,
分子量为120kDa;The molecular weight is 120kDa;
所述海洋藻类为:红藻;The marine algae is: red algae;
所述糖为多糖;The sugar is a polysaccharide;
所述多糖,包括:葡萄糖、甘露糖、鼠李糖、半乳糖;The polysaccharide comprises: glucose, mannose, rhamnose, galactose;
所述蛋白质,包括:天冬氨酸、谷氨酸、甘氨酸、精氨酸、赖氨酸、丝氨酸、苏氨酸。The protein includes: aspartic acid, glutamic acid, glycine, arginine, lysine, serine, threonine.
实施例5一种用于治疗风湿类风湿的药物Embodiment 5 A medicine for treating rheumatoid rheumatoid
所述药物为海洋藻类糖蛋白;The drug is a marine algae glycoprotein;
所述海洋藻类糖蛋白,以重量含量计,包括糖60%,蛋白质32%,The marine algal glycoprotein, which comprises 60% by weight of sugar and 32% by weight,
分子量为400kDa;The molecular weight is 400kDa;
所述海洋藻类为:褐藻;The marine algae is: brown algae;
所述糖为多糖;The sugar is a polysaccharide;
所述多糖,包括:葡萄糖、甘露糖、鼠李糖、半乳糖;The polysaccharide comprises: glucose, mannose, rhamnose, galactose;
所述蛋白质,包括:天冬氨酸、谷氨酸、甘氨酸、精氨酸、赖氨酸、丝氨酸、苏氨酸。The protein includes: aspartic acid, glutamic acid, glycine, arginine, lysine, serine, threonine.
实施例6一种用于治疗风湿类风湿的药物Embodiment 6 A medicine for treating rheumatoid rheumatoid
所述药物为海洋藻类糖蛋白;The drug is a marine algae glycoprotein;
所述海洋藻类糖蛋白,以重量含量计,包括糖99%,蛋白质1%,The marine algae glycoprotein, by weight, comprises 99% sugar, 1% protein,
分子量为3000kDa;The molecular weight is 3000kDa;
所述海洋藻类为:金藻;The marine algae is: gold algae;
所述糖为多糖;The sugar is a polysaccharide;
所述多糖,包括:葡萄糖、甘露糖、鼠李糖、半乳糖;The polysaccharide comprises: glucose, mannose, rhamnose, galactose;
所述蛋白质,包括:天冬氨酸、谷氨酸、甘氨酸、精氨酸、赖氨酸、丝氨酸、苏氨酸。The protein includes: aspartic acid, glutamic acid, glycine, arginine, lysine, serine, threonine.
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。The glycoprotein described in the above Examples 1-6 further includes a pigment; the pigment is a natural pigment contained in the algae substance.
对上述实施例1-6进行概括为:The above embodiments 1-6 are summarized as follows:
一种用于治疗风湿类风湿的药物A medicine for treating rheumatoid rheumatoid
所述药物,为糖蛋白;The drug is a glycoprotein;
所述糖蛋白,以重量含量计,包括糖1-99%,蛋白质1-99%;The glycoprotein, by weight content, comprises 1-99% sugar, 1-99% protein;
分子量为0.2-30000kDa;The molecular weight is 0.2-30000 kDa;
所述糖为多糖; The sugar is a polysaccharide;
所述药物,为合成糖蛋白及合成多糖和蛋白质。The drug is a synthetic glycoprotein and a synthetic polysaccharide and protein.
所述蛋白包括20种氨基酸和8种人工合成氨基酸;The protein comprises 20 amino acids and 8 synthetic amino acids;
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。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.
实施例7一种用于治疗风湿类风湿的药物的应用试验Example 7 Application test of a medicament for treating rheumatoid rheumatoid
试验方法:experiment method:
将造模大鼠进行随机分组:分为空白对照组、模型对照组、本发明组1-6The model rats were randomly divided into two groups: a blank control group, a model control group, and the present invention group 1-6.
共8组,每组10只,除空白对照组外试验第1天开始造模,造模方法为:将大鼠置于6℃冷水中,水深2cm,站立其中20分钟,同时电风扇吹3档风力,每日1次,连续14天;造模第一天,每只造模大鼠注射完全弗氏佐剂0-1ml于右后足跖皮内1次,第19天后,本发明组1-6分别灌胃本发明实施例1-6所述药物,剂量为3g/天,每日3次,连续6天。模型对照组和空白对照组,灌胃生理盐水。A total of 8 groups, 10 in each group, except for the blank control group, began to mold on the first day of the test. The modeling method was as follows: the rats were placed in 6 ° C cold water, the water depth was 2 cm, standing for 20 minutes, and the electric fan was blown 3 Wind speed, once a day for 14 consecutive days; on the first day of modeling, each model rat was injected with 0-1 ml of complete Freund's adjuvant once in the right hind paw, and after 19 days, the invention group 1-6 The medicaments according to Examples 1-6 of the present invention were respectively administered at a dose of 3 g/day, 3 times a day for 6 consecutive days. The model control group and the blank control group were intragastrically administered with normal saline.
关节疼痛的测定:于实验第25天、30天测定各组大鼠右足部关节疼痛;Determination of joint pain: The right foot joint pain of each group was measured on the 25th and 30th day of the experiment;
关节肿胀的测定:于实验第25天、30天分别用游标卡尺测定各组大鼠右足关节直径,按照公式计算:肿胀指数(g/kg)=关节直径(cm)/体重(g)×105 Determination of joint swelling: The right foot joint diameter of each group was measured by vernier caliper on the 25th and 30th day of the experiment, and calculated according to the formula: swelling index (g/kg) = joint diameter (cm) / body weight (g) × 10 5
于实验35天处死动物后,分别分离丘脑、血浆、血清、按试剂盒测定方法,测定下丘脑L-ENK和β-END含量、血浆SP含量、血清免疫球蛋白IgG含量、血清细胞因子IL-1β含量、IL-6含量。After the animals were sacrificed on the 35th day of the experiment, the thalamus, plasma, serum were separated, and the method of kit was used to determine the content of L-ENK and β-END in the hypothalamus, plasma SP content, serum immunoglobulin IgG content, serum cytokine IL- 1β content, IL-6 content.
表1本发明药物对大鼠类风湿性关节炎关节疼痛的影响Table 1 Effect of the drug of the present invention on joint pain in rat rheumatoid arthritis
组别Group 第25天/gDay 25 / g 第30天/gDay 30 / g
空白对照组Blank control group 1545.10±90.81545.10±90.8 1230.2±70.31230.2±70.3
模型对照组Model control group 1052.2±105.81052.2±105.8 836.7±80.3836.7±80.3
实施例1Example 1 1152±85.41152±85.4 870.6±73.3870.6±73.3
实施例2Example 2 1162±86.41162±86.4 915.9±72.5915.9±72.5
实施例3Example 3 1186±75.41186±75.4 945.7±85.4945.7±85.4
实施例4Example 4 1160±79.11160±79.1 923.8±76.0923.8±76.0
实施例5Example 5 1158±69.71158±69.7 912.4±79.2912.4±79.2
实施例6Example 6 1147±70.21147±70.2 870.6±84.6870.6±84.6
本发明药物能有效缓解大鼠类风湿性关节炎的关节疼痛,关节痛阈值显著升高,试验第25天,关节痛阈值为1147-1186g,试验第30天,关节痛阈值为870.6-945.7g;The medicine of the invention can effectively relieve joint pain of rheumatoid arthritis in rats, and the threshold of joint pain is significantly increased. On the 25th day of the experiment, the joint pain threshold is 1147-1186g, and the joint pain threshold is 870.6-945.7g on the 30th day of the experiment. ;
表2本发明药物对大鼠类风湿性关节炎关节肿胀的影响Table 2 Effect of the drug of the present invention on joint swelling of rat rheumatoid arthritis
组别Group 第25天(m/kg)Day 25 (m/kg) 第30天(m/kg)Day 30 (m/kg)
空白对照组Blank control group 190.1±25.8190.1±25.8 175.2±35.7175.2±35.7
模型对照组Model control group 350.3±21.6350.3±21.6 300.5±34.9300.5±34.9
实施例1Example 1 330.5±22.9330.5±22.9 270.5±33.4270.5±33.4
实施例2Example 2 326.1±24.1326.1±24.1 251.4±33.5251.4±33.5
实施例3Example 3 300.3±25.4300.3±25.4 231.8±32.7231.8±32.7
实施例4Example 4 312.4±23.6312.4±23.6 241.6±28.1241.6±28.1
实施例5Example 5 326.7±22.9326.7±22.9 256.7±27.1256.7±27.1
实施例6Example 6 330.2±21.7330.2±21.7 270.1±26.5270.1±26.5
本发明药物对大鼠类风湿性关节炎关节肿胀有明显缓解作用,试验第25天,本发明组动物右关节肿胀指数显著降低,为300.3-330.5m/kg;试验第30天,动物右关节肿胀指数为231.8-270.5m/kg。The medicine of the invention has obvious remission effect on joint swelling of rat rheumatoid arthritis. On the 25th day of the experiment, the swelling index of the right joint of the animal of the invention group is significantly reduced, which is 300.3-330.5 m/kg; on the 30th day of the experiment, the right joint of the animal The swelling index is 231.8-270.5 m/kg.
表3本发明药物对L-ENK、β-END、SP、IgG、IL-1β、IL-6的影响Table 3 Effect of the drug of the present invention on L-ENK, β-END, SP, IgG, IL-1β, IL-6
[根据细则26改正13.03.2017] 
Figure WO-DOC-TABLE-3
[Correct according to Rule 26 13.03.2017]
Figure WO-DOC-TABLE-3
本发明药物能提高大鼠下丘脑L-ENK、β-END含量,两者均有镇痛作用,降低促炎症因子IL-1β、IL-6的分泌,抑制血清免疫球蛋白IgG的合成和分泌,抑制痛兴奋因子SP的释放,L-ENK含量为170.1-212.6pg/g,β-END含量为135.6-170.6pg/g,SP含量为60.3-67.5ng/L,IgG含量为12.00-12.58g/L,IL-1β 含量为0.200-0.231mg/L,IL-6含量为40.15-45.56ng/L。The medicine of the invention can increase the content of L-ENK and β-END in the hypothalamus of rats, both of which have analgesic effect, reduce the secretion of pro-inflammatory factors IL-1β and IL-6, and inhibit the synthesis and secretion of serum immunoglobulin IgG. To inhibit the release of SP, the L-ENK content is 170.1-212.6pg/g, the β-END content is 135.6-170.6pg/g, the SP content is 60.3-67.5ng/L, and the IgG content is 12.00-12.58g. /L, IL-1β The content is 0.200-0.231 mg/L, and the IL-6 content is 40.15-45.56 ng/L.
实施例8一种用于治疗风湿类风湿的药物Embodiment 8 A medicine for treating rheumatoid rheumatoid
包括海洋藻类糖蛋白1份、葡萄糖醛酸1份;Including 1 part of marine algae glycoprotein and 1 part of glucuronic acid;
所述海洋藻类糖蛋白,以重量含量计,包括糖9%,蛋白质80%,The marine algae glycoprotein, which comprises 9% sugar and 80% protein by weight,
分子量为8kDa;The molecular weight is 8kDa;
所述海洋藻类为:小球藻;The marine algae is: chlorella;
所述糖为多糖;The sugar is a polysaccharide;
所述多糖,包括:葡萄糖、甘露糖、鼠李糖、半乳糖;The polysaccharide comprises: glucose, mannose, rhamnose, galactose;
所述蛋白质,包括:天冬氨酸、谷氨酸、甘氨酸、精氨酸、赖氨酸、丝氨酸、苏氨酸。The protein includes: aspartic acid, glutamic acid, glycine, arginine, lysine, serine, threonine.
实施例9一种用于治疗风湿类风湿的药物Embodiment 9 A medicine for treating rheumatoid rheumatoid
同实施例8,只改变海洋藻类糖蛋白和葡萄糖醛酸的配比,改变为:In the same manner as in Example 8, only the ratio of marine algae glycoprotein to glucuronic acid was changed, and it was changed to:
所述药物包括海洋藻类糖蛋白24份、葡萄糖醛酸8份。The drug includes 24 parts of marine algae glycoprotein and 8 parts of glucuronic acid.
实施例10一种用于治疗风湿类风湿的药物Embodiment 10 A medicament for treating rheumatoid rheumatoid
同实施例8,只改变海洋藻类糖蛋白和葡萄糖醛酸的配比,改变为:In the same manner as in Example 8, only the ratio of marine algae glycoprotein to glucuronic acid was changed, and it was changed to:
所述药物包括海洋藻类糖蛋白57份、葡萄糖醛酸16份。The drug includes 57 parts of marine algae glycoprotein and 16 parts of glucuronic acid.
实施例11一种用于治疗风湿类风湿的药物Embodiment 11 A medicament for treating rheumatoid rheumatoid
同实施例8,只改变海洋藻类糖蛋白和葡萄糖醛酸的配比,改变为:In the same manner as in Example 8, only the ratio of marine algae glycoprotein to glucuronic acid was changed, and it was changed to:
所述药物包括海洋藻类糖蛋白99份、葡萄糖醛酸28份。The drug includes 99 parts of marine algae glycoprotein and 28 parts of glucuronic acid.
实施例12一种用于治疗风湿类风湿的药物Embodiment 12 A medicament for treating rheumatoid rheumatoid
以重量含量计,包括海洋藻类糖蛋白1份、葡萄糖醛酸1份、青黛3份。In terms of weight content, 1 part of marine algae glycoprotein, 1 part of glucuronic acid, and 3 parts of barley.
所述海洋藻类糖蛋白,以重量含量计,包括糖16%,蛋白质80%,The marine algae glycoprotein, which comprises, by weight, 16% sugar, 80% protein,
分子量为12kDa;The molecular weight is 12kDa;
所述海洋藻类为:螺旋藻;The marine algae is: spirulina;
所述糖为多糖;The sugar is a polysaccharide;
所述多糖,包括:葡萄糖、甘露糖、鼠李糖、半乳糖;The polysaccharide comprises: glucose, mannose, rhamnose, galactose;
所述蛋白质,包括:天冬氨酸、谷氨酸、甘氨酸、精氨酸、赖氨酸、丝氨酸、苏氨酸。The protein includes: aspartic acid, glutamic acid, glycine, arginine, lysine, serine, threonine.
实施例13一种用于治疗风湿类风湿的药物Embodiment 13 A medicament for treating rheumatoid rheumatoid
同实施例12,只改变海洋藻类糖蛋白、葡萄糖醛酸、青黛的重量配比,改变为:In the same manner as in the example 12, only the weight ratio of the marine algae glycoprotein, glucuronic acid, and barley was changed, and the change was:
以重量份计,所述药物包括海洋藻类糖蛋白34份、葡萄糖醛酸8份、青黛5份。The drug includes 34 parts of marine algae glycoprotein, 8 parts of glucuronic acid, and 5 parts of barley in parts by weight.
实施例14一种用于治疗风湿类风湿的药物 Embodiment 14 A medicament for treating rheumatoid rheumatoid
同实施例12,只改变海洋藻类糖蛋白、葡萄糖醛酸、青黛的重量配比,改变为:In the same manner as in the example 12, only the weight ratio of the marine algae glycoprotein, glucuronic acid, and barley was changed, and the change was:
以重量份计,所述药物包括海洋藻类糖蛋白59份、葡萄糖醛酸18份、青黛8份。The drug includes 59 parts of marine algae glycoprotein, 18 parts of glucuronic acid, and 8 parts of barley in parts by weight.
实施例15一种用于治疗风湿类风湿的药物Embodiment 15 A medicament for treating rheumatoid rheumatoid
同实施例12,只改变海洋藻类糖蛋白、葡萄糖醛酸、青黛的重量配比,改变为:In the same manner as in the example 12, only the weight ratio of the marine algae glycoprotein, glucuronic acid, and barley was changed, and the change was:
以重量份计,所述药物包括海洋藻类糖蛋白99份、葡萄糖醛酸23份、青黛11份。The drug includes 99 parts of marine algae glycoprotein, 23 parts of glucuronic acid, and 11 parts of barley in parts by weight.
上述实施例8-实施例15所述药物在治疗风湿中的应用:The use of the drugs of the above embodiments 8 - 15 in the treatment of rheumatism:
采用实施例7所述的试验方法,改变之处为采用实施例8-实施例15所述药物,进行实验,应用效果如下:Using the test method described in Example 7, the modification was carried out by using the drugs described in Example 8 - Example 15, and the application effects were as follows:
表4本发明药物对大鼠类风湿性关节炎关节疼痛的影响Table 4 Effect of the drug of the present invention on joint pain in rat rheumatoid arthritis
组别Group 第25天/gDay 25 / g 第30天/gDay 30 / g
空白对照组Blank control group 1545.10±90.81545.10±90.8 1230.2±70.31230.2±70.3
模型对照组Model control group 1052.2±105.81052.2±105.8 836.7±80.3836.7±80.3
实施例8Example 8 1180±83.71180±83.7 900.6±74.3900.6±74.3
实施例9Example 9 1256±86.91256±86.9 915.9±72.5915.9±72.5
实施例10Example 10 1486±75.71486±75.7 1189.7±75.41189.7±75.4
实施例11Example 11 1260±75.11260±75.1 956.8±74.0956.8±74.0
实施例12Example 12 1188±66.71188±66.7 965.4±75.3965.4±75.3
实施例13Example 13 1252±71.21252±71.2 941.6±84.8941.6±84.8
实施例14Example 14 1435±68.41435±68.4 1192.4±75.81192.4±75.8
实施例15Example 15 1264±66.41264±66.4 956.5±71.9956.5±71.9
表5本发明药物对大鼠类风湿性关节炎关节肿胀的影响 Table 5 Effect of the drug of the present invention on joint swelling of rat rheumatoid arthritis
组别Group 第25天(m/kg)Day 25 (m/kg) 第30天(m/kg)Day 30 (m/kg)
空白对照组Blank control group 190.1±25.8190.1±25.8 175.2±35.7175.2±35.7
模型对照组Model control group 350.3±21.6350.3±21.6 300.5±34.9300.5±34.9
实施例8Example 8 305.5±22.9305.5±22.9 235.4±33.4235.4±33.4
实施例9Example 9 306.1±23.1306.1±23.1 231.4±30.5231.4±30.5
实施例10Example 10 224.6±25.4224.6±25.4 195.7±31.7195.7±31.7
实施例11Example 11 302.4±22.6302.4±22.6 221.6±29.2221.6±29.2
实施例12Example 12 306.7±21.4306.7±21.4 226.7±27.6226.7±27.6
实施例13Example 13 316.2±22.5316.2±22.5 230.1±26.8230.1±26.8
实施例14Example 14 218.9±22.9218.9±22.9 190.7±27.4190.7±27.4
实施例15Example 15 315.8±21.5315.8±21.5 220.7±27.8220.7±27.8
表6本发明药物对L-ENK、β-END、SP、IgG、IL-1β、IL-6的影响Table 6 Effect of the drug of the present invention on L-ENK, β-END, SP, IgG, IL-1β, IL-6
组别Group L-ENKL-ENK β-ENDβ-END SpSp IgGIgG IL-1βIL-1β IL-6IL-6
空白对照组Blank control group 95.295.2 113.2113.2 50.250.2 9.549.54 0.1150.115 30.5630.56
模型对照组Model control group 150.6150.6 119.5119.5 70.870.8 13.8913.89 0.1850.185 48.8948.89
实施例8Example 8 190.6190.6 185.6185.6 57.557.5 11.5811.58 0.1800.180 35.5635.56
实施例9Example 9 192.3192.3 180.8180.8 56.256.2 11.1411.14 0.1200.120 32.3132.31
实施例10Example 10 260.7260.7 350.6350.6 48.348.3 7.67.6 0.2000.200 20.1520.15
实施例11Example 11 192.6192.6 183.8183.8 55.955.9 11.3511.35 0.1860.186 34.8934.89
实施例12Example 12 190.7190.7 189.4189.4 56.756.7 10.4210.42 0.1790.179 35.5235.52
实施例13Example 13 190.1190.1 190.7190.7 55.355.3 10.5210.52 0.1190.119 36.5836.58
实施例14Example 14 272.4272.4 345.9345.9 47.647.6 7.87.8 0.1850.185 22.6822.68
实施例15Example 15 196.5196.5 195.4195.4 56.256.2 11.0011.00 0.1820.182 35.7935.79
实施例8-11,只改变海洋藻类糖蛋白和葡萄糖醛酸的重量配比,通过实验结果可知,实施例10是最优选的实施例;In Examples 8-11, only the weight ratio of marine algae glycoprotein and glucuronic acid was changed. From the experimental results, Example 10 is the most preferred embodiment;
实施例12-15只改变海洋藻类糖蛋白、葡萄糖醛酸、青黛的重量配比,通过实验结果可知,实施例14是最优选的实施例;Examples 12-15 only changed the weight ratio of marine algae glycoprotein, glucuronic acid, and strontium. From the experimental results, Example 14 is the most preferred embodiment;
实施例16一种用于治疗风湿类风湿的药物 Embodiment 16 A medicament for treating rheumatoid rheumatoid
以重量含量计,包括海洋藻类糖蛋白1份、青黛5份、灸甘草6份、葡萄糖醛酸1份。In terms of weight content, it includes 1 part of marine algae glycoprotein, 5 parts of green barley, 6 parts of moxibustion licorice, and 1 part of glucuronic acid.
所述海洋藻类糖蛋白,以重量含量计,包括糖30%,蛋白质50%,The marine algae glycoprotein, including 30% sugar, 50% protein, by weight
分子量为20kDa;The molecular weight is 20kDa;
所述海洋藻类为:长叶紫菜;The marine algae is: long-leaved laver;
所述糖为多糖;The sugar is a polysaccharide;
所述多糖,包括:葡萄糖、甘露糖、鼠李糖、半乳糖;The polysaccharide comprises: glucose, mannose, rhamnose, galactose;
所述蛋白质,包括:天冬氨酸、谷氨酸、甘氨酸、精氨酸、赖氨酸、丝氨酸、苏氨酸。The protein includes: aspartic acid, glutamic acid, glycine, arginine, lysine, serine, threonine.
实施例17一种用于治疗风湿类风湿的药物Embodiment 17 A medicament for treating rheumatoid rheumatoid
同实施例16,只改变海洋藻类糖蛋白、青黛、灸甘草、葡萄糖醛酸的重量份配比,改变为:In the same manner as in Example 16, only the weight ratio of marine algae glycoprotein, barley, moxibustion, and glucuronic acid was changed, and the change was:
以重量含量计,包括海洋藻类糖蛋白47份、青黛8份、灸甘草12份、葡萄糖醛酸15份。In terms of weight, it includes 47 parts of marine algae glycoprotein, 8 parts of barley, 12 parts of mojib licorice, and 15 parts of glucuronic acid.
实施例18一种用于治疗风湿类风湿的药物Embodiment 18 A medicament for treating rheumatoid rheumatoid
同实施例16,只改变海洋藻类糖蛋白、青黛、灸甘草、葡萄糖醛酸的重量份配比,改变为:In the same manner as in Example 16, only the weight ratio of marine algae glycoprotein, barley, moxibustion, and glucuronic acid was changed, and the change was:
以重量含量计,包括海洋藻类糖蛋白99份、青黛13份、灸甘草14份、葡萄糖醛酸17份。In terms of weight, it includes 99 parts of marine algae glycoprotein, 13 parts of green barley, 14 parts of moxibustion licorice, and 17 parts of glucuronic acid.
实施例19一种用于治疗风湿类风湿的药物Embodiment 19 A medicament for treating rheumatoid rheumatoid
以重量份计,包括海洋藻类糖蛋白1份、青黛5份、灸甘草6份、延胡索7份、连翘5份。所述海洋藻类糖蛋白,以重量含量计,包括糖50%,蛋白质20%,In parts by weight, including 1 part of marine algae glycoprotein, 5 parts of green barley, 6 parts of moxibustion licorice, 7 parts of Corydalis, and 5 parts of Forsythia. The marine algae glycoprotein, which comprises 50% by weight of sugar and 20% by weight of protein,
分子量为200kDa;The molecular weight is 200kDa;
所述海洋藻类为:马尾藻;The marine algae is: Sargassum;
所述糖为多糖;The sugar is a polysaccharide;
所述多糖,包括:葡萄糖、甘露糖、鼠李糖、半乳糖;The polysaccharide comprises: glucose, mannose, rhamnose, galactose;
所述蛋白质,包括:天冬氨酸、谷氨酸、甘氨酸、精氨酸、赖氨酸、丝氨酸、苏氨酸。The protein includes: aspartic acid, glutamic acid, glycine, arginine, lysine, serine, threonine.
实施例20一种用于治疗风湿类风湿的药物Embodiment 20 A medicament for treating rheumatoid rheumatoid
同实施例19,只改变海洋藻类糖蛋白、青黛、灸甘草、延胡索、连翘的重量配比,改变为:In the same manner as in the embodiment 19, only the weight ratio of the marine algae glycoprotein, the barley, the mozzarella, the corydalis, and the forsythia is changed, and the change is:
以重量份计,包括海洋藻类糖蛋白68份、青黛12份、灸甘草11份、延胡索8份、连翘9份。In parts by weight, including 68 parts of marine algae glycoprotein, 12 parts of green barley, 11 parts of moxibustion licorice, 8 parts of Corydalis, and 9 parts of forsythia.
实施例21一种用于治疗风湿类风湿的药物Embodiment 21 A medicament for treating rheumatoid rheumatoid
同实施例19,只改变海洋藻类糖蛋白、青黛、灸甘草、延胡索、连翘的重量配比,改变为: In the same manner as in the embodiment 19, only the weight ratio of the marine algae glycoprotein, the barley, the mozzarella, the corydalis, and the forsythia is changed, and the change is:
以重量份计,包括海洋藻类糖蛋白99份、青黛13份、灸甘草14份、延胡索12份、连翘10份。In parts by weight, including 99 parts of marine algae glycoprotein, 13 parts of green barley, 14 parts of moxibustion licorice, 12 parts of Corydalis, and 10 parts of forsythia.
上述实施例16-实施例21所述药物在治疗风湿中的应用:The use of the drugs of the above embodiments 16 to 21 in the treatment of rheumatism:
采用实施例7所述的试验方法,改变之处为采用实施例16-实施例21所述药物,应用效果如下:The test method described in Example 7 was adopted, and the modification was carried out by using the drugs described in Example 16 to Example 21, and the application effects were as follows:
表7本发明药物对大鼠类风湿性关节炎关节疼痛的影响Table 7 Effect of the drug of the present invention on joint pain in rat rheumatoid arthritis
组别Group 第25天/gDay 25 / g 第30天/gDay 30 / g
空白对照组Blank control group 1545.10±90.81545.10±90.8 1230.2±70.31230.2±70.3
模型对照组Model control group 1052.2±105.81052.2±105.8 836.7±80.7836.7±80.7
实施例16Example 16 1280±83.71280±83.7 940.6±74.9940.6±74.9
实施例17Example 17 1536±86.91536±86.9 1225.9±72.81225.9±72.8
实施例18Example 18 1236±73.71236±73.7 935.7±73.4935.7±73.4
实施例19Example 19 1275±72.11275±72.1 976.8±76.0976.8±76.0
实施例20Example 20 1528±68.71528±68.7 1227.4±77.31227.4±77.3
实施例21Example 21 1252±72.21252±72.2 971.6±82.8971.6±82.8
表8本发明药物对大鼠类风湿性关节炎关节肿胀的影响Table 8 Effect of the drug of the present invention on joint swelling of rat rheumatoid arthritis
组别Group 第25天(m/kg)Day 25 (m/kg) 第30天(m/kg)Day 30 (m/kg)
空白对照组Blank control group 190.1±25.8190.1±25.8 175.2±35.7175.2±35.7
模型对照组Model control group 350.3±21.6350.3±21.6 300.5±34.9300.5±34.9
实施例16Example 16 298.5±20.9298.5±20.9 200.4±23.4200.4±23.4
实施例17Example 17 192.1±20.1192.1±20.1 178.4±20.5178.4±20.5
实施例18Example 18 294.6±23.4294.6±23.4 205.7±21.7205.7±21.7
实施例19Example 19 302.4±22.8302.4±22.8 211.6±26.2211.6±26.2
实施例20Example 20 195.7±21.9195.7±21.9 176.7±25.6176.7±25.6
实施例21Example 21 292.2±22.5292.2±22.5 210.1±23.8210.1±23.8
表9本发明药物对L-ENK、β-END、SP、IgG、IL-1β、IL-6的影响 Table 9 Effect of the drug of the present invention on L-ENK, β-END, SP, IgG, IL-1β, IL-6
组别Group L-ENKL-ENK β-ENDβ-END SpSp IgGIgG IL-1βIL-1β IL-6IL-6
空白对照组Blank control group 95.295.2 113.2113.2 50.250.2 9.549.54 0.1150.115 30.5630.56
模型对照组Model control group 150.6150.6 119.5119.5 70.870.8 13.8913.89 0.1850.185 48.8948.89
实施例16Example 16 200.6200.6 205.6205.6 52.552.5 10.2810.28 0.1700.170 30.5630.56
实施例17Example 17 302.3302.3 380.8380.8 45.245.2 7.117.11 0.1130.113 20.2520.25
实施例18Example 18 210.7210.7 215.6215.6 53.353.3 10.1310.13 0.1750.175 30.1530.15
实施例19Example 19 200.6200.6 218.8218.8 52.952.9 10.0310.03 0.1760.176 31.8931.89
实施例20Example 20 304.7304.7 375.4375.4 45.745.7 7.097.09 0.1150.115 21.5221.52
实施例21Example 21 211.1211.1 216.7216.7 53.353.3 10.0210.02 0.1790.179 31.5831.58
实施例16-18,只改变海洋藻类糖蛋白、青黛、灸甘草、葡萄糖醛酸的重量份配比,通过实验结果可知,实施例17是最优选的实施例;In Examples 16-18, only the weight ratio of marine algae glycoprotein, barley, moxibustion, and glucuronic acid was changed. From the experimental results, Example 17 is the most preferred embodiment;
实施例19-21,只改变海洋藻类糖蛋白、青黛、灸甘草、延胡索、连翘的重量配比,通过实验结果可知,实施例20是最优选的实施例。In Examples 19-21, only the weight ratio of marine algae glycoprotein, barley, moxibustion licorice, Corydalis, and forsythia was changed. From the experimental results, Example 20 is the most preferred embodiment.
实施例22一种用于治疗风湿类风湿的药物Embodiment 22 A medicament for treating rheumatoid rheumatoid
以重量份计,包括以下组分:In parts by weight, the following components are included:
海洋藻类糖蛋白70份、缬草5份、谷精草2份、白芍3份、车前子5份、马齿苋4份、葛根7份、山慈姑9份、土茯苓10份。70 parts of marine algae glycoprotein, 5 parts of valerian, 2 parts of glutinous rice grass, 3 parts of white peony, 5 parts of psyllium, 4 parts of purslane, 7 parts of puerarin, 9 parts of sage, and 10 parts of scorpion.
所述海洋藻类糖蛋白,以重量含量计,包括糖8%,蛋白质80%,The marine algae glycoprotein, which comprises 8% sugar and 80% protein by weight,
分子量为10kDa;The molecular weight is 10kDa;
所述海洋藻类为:小球藻;The marine algae is: chlorella;
所述糖,以重量份计,包括如下组分:葡萄糖55份、甘露糖20份、鼠李糖13份、半乳糖8份;The sugar, in parts by weight, comprises the following components: 55 parts of glucose, 20 parts of mannose, 13 parts of rhamnose, and 8 parts of galactose;
所述蛋白质,以重量份计,包括如下组分:天冬氨酸13份、谷氨酸11份、甘氨酸8份。The protein, in parts by weight, includes the following components: 13 parts of aspartic acid, 11 parts of glutamic acid, and 8 parts of glycine.
采用实施例7的试验方法,采用实施例22所述药物,进行实验,结果为:Using the test method of Example 7, the experiment was carried out using the drug of Example 22, and the results were as follows:
试验第25天,关节痛阈值为1450g,试验第30天,关节痛阈值为1125g;On the 25th day of the experiment, the joint pain threshold was 1450g, and the joint pain threshold was 1125g on the 30th day of the experiment;
试验第25天,本发明组动物右关节肿胀指数显著降低,为212.3m/kg;试验第30天,动物右关节肿胀指数为185.6m/kg。On the 25th day of the experiment, the swelling index of the right joint of the animals of the present invention was significantly decreased to 212.3 m/kg; on the 30th day of the experiment, the index of swelling of the right joint of the animals was 185.6 m/kg.
L-ENK含量为289.6pg/g,β-END含量为382.3pg/g,SP含量为50.3ng/L,IgG含量为9.65g/L,IL-1β含量为0.135mg/L,IL-6含量为23.56ng/L。The L-ENK content was 289.6 pg/g, the β-END content was 382.3 pg/g, the SP content was 50.3 ng/L, the IgG content was 9.65 g/L, the IL-1β content was 0.135 mg/L, and the IL-6 content was It is 23.56 ng/L.
实施例23一种用于治疗风湿类风湿的药物的制备方法: Example 23 A method for preparing a medicament for treating rheumatoid rheumatoid arthritis:
步骤1、称量Step 1, weighing
按照配方称量海洋藻类糖蛋白和各中药成分;Weigh the marine algae glycoprotein and each Chinese medicine ingredient according to the formula;
步骤2、中药的浸提Step 2, Chinese medicine leaching
(1)清洗(1) Cleaning
将各中药成分,用清水冲洗,去处杂质;Wash each Chinese medicine ingredient with water to remove impurities;
(2)粉碎、微波萃取(2) pulverization, microwave extraction
将中药粉碎处理成100目药材粉末,加入10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;The traditional Chinese medicine is pulverized into 100 mesh medicinal material powder, 10 times of 50% ethanol is added, the temperature is controlled to 60 ° C, microwave irradiation with 260 W microwave power, microwave wavelength of 130 mm, frequency of 1200 MHz for 5 min, filtration, and the filtrate is collected;
分离药渣,加入12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;Separating the dregs, adding 12 volumes of clean water, controlling the temperature to 50 ° C, using microwave power of 200 W, microwave wavelength of 140 mm, microwave irradiation at a frequency of 1250 MHz for 5 min, filtering, collecting the filtrate;
合并两次的滤液;经过0.45μm微孔滤膜过滤,得滤液,所得续滤液经蠕动泵导入Büchi290小型喷雾干燥器的双流向螺旋式喷嘴,控制进口温度为125℃,进料速度为3mL/min,喷雾干燥制得中药粉末。The filtrates were combined twice; filtered through a 0.45 μm microporous membrane to obtain a filtrate. The obtained filtrate was introduced into a double flow spiral nozzle of a Büchi290 small spray dryer via a peristaltic pump, and the inlet temperature was controlled at 125 ° C, and the feed rate was 3 mL / Min, spray drying to obtain a traditional Chinese medicine powder.
步骤3、加入海洋藻类糖蛋白Step 3. Add marine algae glycoprotein
海洋藻类糖蛋白粉末和上述中药粉末混合均匀,制备胶囊、片剂等不同剂型。The marine algae glycoprotein powder and the above traditional Chinese medicine powder are uniformly mixed to prepare different dosage forms such as capsules and tablets.
本发明所述药物,pH为5.3-9.8之间,优选为6.5-7.5之间。The medicament of the present invention has a pH of between 5.3 and 9.8, preferably between 6.5 and 7.5.
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。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.
实施例24一种用于治疗风湿类风湿的药物Embodiment 24 A medicament for treating rheumatoid rheumatoid
所述药物,为多糖、蛋白质的混合物;The drug is a mixture of polysaccharides and proteins;
所述药物,以重量份计,包括多糖1-99%、蛋白质1-99%;The drug, in parts by weight, comprises 1-99% polysaccharide, 1-99% protein;
所述多糖,包括:葡萄糖、甘露糖、鼠李糖、半乳糖;The polysaccharide comprises: glucose, mannose, rhamnose, galactose;
所述蛋白质,包括:天冬酰胺、半胱氨酸、赖氨酸、精氨酸、丝氨酸、苏氨酸、丙氨酸、天冬氨酸、谷氨酰胺、谷氨酸、组氨酸、异亮氨酸、甘氨酸、亮氨酸、甲硫氨酸、苯丙氨酸、脯氨酸、酪氨酸、缬氨酸。The protein comprises: asparagine, cysteine, lysine, arginine, serine, threonine, alanine, aspartic acid, glutamine, glutamic acid, histidine, Isoleucine, glycine, leucine, methionine, phenylalanine, valine, tyrosine, valine.
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。The polysaccharide and protein mixture, the polysaccharide has a molecular weight of 0.2-3000 kDa, and the protein has a molecular weight of 0.2-3000 kDa.
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;a mixture of the polysaccharide and the protein, further a mixture of an algal polysaccharide and an algal protein;
所述藻类多糖和藻类蛋白的混合物,还包括色素;a mixture of the algal polysaccharide and the algal protein, further comprising a pigment;
所述色素为藻类物质中含有的天然色素; The pigment is a natural pigment contained in an algae substance;
所述藻类蛋白可以是藻蓝蛋白、藻红蛋白或藻黄色蛋白。The algal protein may be phycocyanin, phycoerythrin or phycoerythrin.
所述糖蛋白包括合成糖蛋白及合成多糖、蛋白。The glycoproteins include synthetic glycoproteins and synthetic polysaccharides and proteins.
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。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.
本发明所述药物,还可以是保健品或食品。The medicament of the present invention may also be a health care product or a food.
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。 The basic principles and main features of the present invention and the advantages of the present invention are shown and described above. It should be understood by those skilled in the art that the present invention is not limited by the foregoing embodiments, and that the present invention is only described in the foregoing description and the description of the present invention, without departing from the spirit and scope of the invention. Various changes and modifications are intended to be included within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and their equivalents.

Claims (10)

  1. 一种用于治疗风湿类风湿的药物,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。A medicament for treating rheumatoid rheumatoid, characterized in that the medicament is a glycoprotein or a mixture or polypeptide or protein of a polysaccharide and a protein.
  2. 根据权利要求1所述的一种用于治疗风湿类风湿的药物,其特征在于:所述药物为海洋藻类糖蛋白。A medicament for treating rheumatoid rheumatoid according to claim 1, wherein the medicament is a marine algae glycoprotein.
  3. 根据权利要求2所述的一种用于治疗风湿类风湿的药物,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%。A medicament for treating rheumatoid rheumatoid according to claim 2, wherein said glycoprotein comprises, by weight, 1-99% sugar, 1-99% protein; said marine algae sugar The protein, by weight, comprises 1-99% sugar, 1-99% protein; a mixture of the polysaccharide and protein, including 1-99% sugar, 1-99% protein by weight.
  4. 根据权利要求2所述的一种用于治疗风湿类风湿的药物,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。A medicament for treating rheumatoid rheumatoid according to claim 2, wherein said glycoprotein has a molecular weight of 0.2 to 3000 kDa; said marine algal glycoprotein has a molecular weight of 0.2 to 3000 kDa; said polysaccharide and A mixture of proteins, the molecular weight of the polysaccharide is 0.2-3000 kDa, and the molecular weight of the protein is 0.2-3000 kDa.
  5. 根据权利要求1所述的一种用于治疗风湿类风湿的药物,其特征在于:以重量含量计,包括糖蛋白1-99份、葡萄糖醛酸1-23份。A medicament for treating rheumatoid rheumatoid according to claim 1, characterized in that it comprises, by weight, 1-99 parts of glycoprotein and 1-23 parts of glucuronic acid.
  6. 根据权利要求1所述的一种用于治疗风湿类风湿的药物,其特征在于:以重量含量计,包括糖蛋白1-99份、葡萄糖醛酸1-23份、青黛3-11份。A medicament for treating rheumatoid rheumatoid according to claim 1, which comprises, by weight, 1-99 parts of glycoprotein, 1-23 parts of glucuronic acid, and 3-11 parts of barley.
  7. 根据权利要求1所述的一种用于治疗风湿类风湿的药物,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。The medicament for treating rheumatoid rheumatoid according to claim 1, wherein the algae is one or more of cyanobacteria, green algae, red algae, gold algae, and brown algae.
  8. 根据权利要求1所述的一种用于治疗风湿类风湿的药物,其特征在于:以重量含量计,包括糖蛋白1-99份、青黛5-13份、灸甘草6-14份、葡萄糖醛酸1-17份。A medicament for treating rheumatoid rheumatoid according to claim 1, characterized in that it comprises, by weight, 1-99 parts of glycoprotein, 5-13 parts of medlar, 6-14 parts of moxibustion licorice, and glucose aldehyde. 1-17 parts of acid.
  9. 根据权利要求1所述的一种用于治疗风湿类风湿的药物,其特征在于:以重量含量计,包括糖蛋白1-99份、青黛5-13份、灸甘草6-14份、延胡索7-12份、连翘5-10份。The medicament for treating rheumatoid rheumatoid according to claim 1, characterized in that: by weight content, 1-99 parts of glycoprotein, 5-13 parts of barley, 6-14 parts of moxibustion, and Corydalis 7 -12 parts, forsythia 5-10 parts.
  10. 根据权利要求5-9任一项所述的一种用于治疗风湿类风湿的药物,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%。 A medicament for treating rheumatoid rheumatoid according to any one of claims 5-9, characterized in that the glycoprotein, marine algae glycoprotein comprises, by weight, 1-99% sugar, protein 1-99%.
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