WO2017129060A1 - 一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物 - Google Patents

一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物 Download PDF

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WO2017129060A1
WO2017129060A1 PCT/CN2017/071874 CN2017071874W WO2017129060A1 WO 2017129060 A1 WO2017129060 A1 WO 2017129060A1 CN 2017071874 W CN2017071874 W CN 2017071874W WO 2017129060 A1 WO2017129060 A1 WO 2017129060A1
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parts
glycoprotein
weight
protein
medicament
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PCT/CN2017/071874
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English (en)
French (fr)
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徐宝贞
程龙
程潜
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山东中海制药有限公司
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/02—Peptides of undefined number of amino acids; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7012—Compounds 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/748—Cyanobacteria, i.e. blue-green bacteria or blue-green algae, e.g. spirulina
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/02—Algae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/02—Algae
    • A61K36/04—Rhodophycota or rhodophyta (red algae), e.g. Porphyra
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/02—Algae
    • A61K36/05—Chlorophycota or chlorophyta (green algae), e.g. Chlorella
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/13—Coniferophyta (gymnosperms)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/19—Acanthaceae (Acanthus family)
    • A61K36/195—Strobilanthes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
    • A61K36/315—Isatis, e.g. Dyer's woad
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/484—Glycyrrhiza (licorice)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
    • A61K36/704—Polygonum, e.g. knotweed

Definitions

  • the invention relates to a medicament for treating influenza, upper respiratory tract infection and viral pneumonia, and belongs to the technical field of medicine.
  • Influenza is an acute respiratory infection caused by influenza virus, and it is also a disease that is highly contagious and spreads rapidly. It is mainly transmitted by droplets in the air, contact between people or contact with contaminated objects. The typical clinical symptoms are: high fever, generalized pain, significant fatigue and mild respiratory symptoms. Generally, the autumn and winter seasons are high, and the complications and deaths are very serious.
  • Patent “Composition of anti-influenza H1N1 virus using ultrafiltration and preparation method thereof” patent number: KR101485982 (B1), discloses that ginseng polysaccharide has immunological activity and anti-influenza activity;
  • Patent No. JP2014105202 discloses providing an anti-influenza virus antibody, including a polysaccharide, wherein the basic structure of the sugar residue comprises galactose, mannose and galactose, and the galactose content is preferably 50-79. %, the antibody significantly inhibits the action of influenza A virus in the lungs and respiratory tract;
  • Patent No. US2015335728 discloses an immunogenic composition containing a partially glycosylated viral glycoprotein as a vaccine against influenza virus
  • X discloses: a salt of the seaweed sulfate, extracted from kelp, is Mannose and glucuronic acid a main chain composed of repeating units, a polysaccharide having a fucoidan sulfate as a branch;
  • the existing flu treatment drugs also have the following defects:
  • the body temperature can not be controlled in a short time, and the body temperature changes greatly;
  • the present invention provides a medicament for treating influenza, upper respiratory tract infection, and viral pneumonia in order to solve the deficiencies in the prior art, to achieve the following objects:
  • the drug of the present invention has a stabilizing effect on the body temperature of the endotoxin-induced rabbit, and the body temperature changes ⁇ 1.10 ° C at 4 hours after the drug;
  • the drug of the invention has obvious antipyretic effect on influenza patients, and the antipyretic time after administration is ⁇ 20h;
  • the medicament of the present invention has obvious remission effects on cough, sore throat, cough, runny nose, headache, nasal congestion, muscle soreness and fatigue of influenza patients.
  • the medicament of the present invention is for treating influenza, has no symptoms of bronchus, pneumonia, tuberculosis, no complications, and reduces the amount of antibiotic used.
  • the present invention adopts the following technical solutions:
  • a medicament for treating influenza, upper respiratory tract infection, viral pneumonia characterized in that the medicament is a glycoprotein, or a mixture or polypeptide or protein of a polysaccharide, the glycoprotein comprises 1-99% of sugar, Protein 1-99%; the mixture of polysaccharide and protein, including by weight, 1-99% polysaccharide, protein 1-99%.
  • 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 1-22 parts of glucuronic acid.
  • the drug comprises, by weight, 1-99 parts of marine algae glycoprotein, 1-22 parts of glucuronic acid, and 2-20 parts of barley.
  • 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, 6-30 parts of medlar, 7-13 parts of moxibustion licorice, and 1-15 parts of glucuronic acid.
  • the medicine comprises, by weight, 1-99 parts of marine algae glycoprotein, 6-30 parts of medlar, 7-13 parts of moxibustion licorice, 5-12 parts of medlar, and 4-10 parts of earth elements.
  • 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 has a stabilizing effect on the body temperature of endotoxin-induced rabbits, and the body temperature increases by 0.20-1.10 ° C at 4 hours after the drug.
  • the drug of the present invention has an obvious antipyretic effect on influenza patients, and the antipyretic time after administration is 13.0-20.0 h, and the fever time of the influenza patients in the blank control group is 30.0 h.
  • the medicament of the present invention has obvious remission effect on cough, sore throat, cough, runny nose, headache, nasal congestion, muscle soreness and fatigue of influenza patients, and the cough relief time is 2-6 hours, sore throat relief time For 2-6h, the cough remission time was 1.5-4h, the runny nose remission time was 1.2-4h, the headache remission time was 0.8-7h, the nasal congestion relief time was 1-5h, and the muscle soreness and fatigue remission time was 1-4h.
  • the medicament of the present invention is used for treating influenza, and there is no symptom of bronchial, pneumonia, and tuberculosis, and the total number of complications is 0, and the amount of antibiotic used is reduced.
  • Example 1 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • the drug is a marine algae glycoprotein
  • the marine algae glycoprotein in parts by weight, comprises 1% sugar, 99% protein,
  • the molecular weight is 0.2 kDa
  • the marine algae is: cyanobacteria
  • the sugar is a polysaccharide
  • the polysaccharide comprises: galactose, sialic acid, mannose, arabinose, rhamnose;
  • the protein comprises: glutamic acid, lysine, hydroxyproline, threonine, arginine;
  • Example 2 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • the drug is a marine algae glycoprotein
  • the marine algae glycoprotein in parts by weight, comprises 6% sugar, 85% protein,
  • the molecular weight is 16kDa
  • the marine algae is: green algae;
  • the sugar is a polysaccharide
  • the polysaccharide comprises: galactose, sialic acid, mannose, arabinose, rhamnose;
  • the protein comprises: glutamic acid, lysine, hydroxyproline, threonine, arginine;
  • Example 3 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • the drug is a marine algae glycoprotein
  • the marine algae glycoprotein in parts by weight, comprises 15% sugar, 74% protein,
  • the molecular weight is 3kDa
  • the marine algae is: cyanobacteria
  • the sugar is a polysaccharide
  • the polysaccharide comprises: galactose, sialic acid, mannose, arabinose, rhamnose;
  • the protein comprises: glutamic acid, lysine, hydroxyproline, threonine, arginine;
  • Example 4 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • the drug is a marine algae glycoprotein
  • the marine algae glycoprotein in parts by weight, comprises 32% sugar, 60% protein,
  • the molecular weight is 120kDa
  • the marine algae is: red algae;
  • the sugar is a polysaccharide
  • the polysaccharide comprises: galactose, sialic acid, mannose, arabinose, rhamnose;
  • the protein comprises: glutamic acid, lysine, hydroxyproline, threonine, arginine;
  • Example 5 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • the drug is a marine algae glycoprotein
  • the marine algae glycoprotein in parts by weight, comprises 75% sugar and 20% protein
  • the molecular weight is 600kDa;
  • the marine algae is: brown algae;
  • the sugar is a polysaccharide
  • the polysaccharide comprises: galactose, sialic acid, mannose, arabinose, rhamnose;
  • the protein comprises: glutamic acid, lysine, hydroxyproline, threonine, arginine;
  • Example 6 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • the drug is a marine algae glycoprotein
  • the marine algae glycoprotein in parts by weight, comprises 99% sugar and 1% protein
  • the molecular weight is 3000kDa
  • the marine algae is: gold algae;
  • the sugar is a polysaccharide
  • the polysaccharide comprises: galactose, sialic acid, mannose, arabinose, rhamnose;
  • the protein includes: glutamic acid, lysine, hydroxyproline, threonine, arginine.
  • 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 processed into capsules, tablets and the like according to a conventional process.
  • the drug of the second embodiment of the present invention is 0.4g / day, 0.8g / day, 1g / day, 2g / day, 4g / day, 8g / day, administered intragastrically three times a day;
  • Positive control drug aspirin effervescent tablets produced by AstraZeneca Pharmaceutical Co., Ltd., batch number is 080217, clinical dosage 1 tablet/day (0.5g per tablet), calculated as 0.017 tablets/kg according to 60 kg body weight. The equivalent dose is 1 g/day for rabbits, three times a day.
  • the healthy rabbits were weighed, the normal anus temperature was measured twice on the day of the test, and the animals with anal temperature of 38.5-39.5 °C and two temperature differences of 0.4 °C were used for testing, 10 rabbits in each group;
  • the Escherichia coli endotoxin at 140 ng/ml/kg was injected into the ear vein of rabbits. After 1 hour, the elevation of the spleen was measured, and the corresponding drugs were administered by intragastric administration according to the adjusted value.
  • the model control group was given the same volume of distilled water.
  • the anus temperature was measured once, 1, 2, and 4 hours after the drug. The difference between the anus temperature and the basic anus temperature measured at different times was the change in body temperature.
  • the drug of the second embodiment of the present invention has a certain inhibitory effect on the increase of body temperature of the rabbit caused by endotoxin at a dose of 0.4-8 g/day, and the preferred dose is 1-4 g/day, more preferably 2 -4 g / day, most preferably 3 g / day.
  • Example 1-6 have a stabilizing effect on the body temperature of endotoxin-induced rabbits, and the body temperature is increased by 0.20-1.10 ° C at 4 h after the drug, and Example 2 and Example 3 are preferred examples.
  • Exclusion criteria pregnancy; pneumonia; severe underlying disease; immunodeficiency; taking antiviral drugs before enrollment; organ failure.
  • Example 1-6 The drugs described in Examples 1-6 have obvious antipyretic effects on influenza patients, and the antipyretic time after administration is 13.0-20.0 h, and the fever time of the influenza patients in the blank control group is 30.0 h.
  • Example 2 and Example 3 are preferred embodiments.
  • Example 1-6 The drugs described in Examples 1-6 have obvious remission effects on cough, sore throat, cough, runny nose, headache, nasal congestion, muscle soreness and fatigue in patients with influenza, and the cough relief time is 2-6 hours, sore throat relief The time is 2-6h, the cough remission time is 1.5-4h, the runny nose remission time is 1.2-4h, the headache remission time is 0.8-7h, the nasal congestion remission time is 1-5h, the muscle soreness and fatigue remission time is 1-4h. .
  • Example 2 and Example 3 are preferred embodiments.
  • the glycoprotein of the present invention is used for treating influenza, and there is no symptom of bronchial, pneumonia or tuberculosis, the total number of complications is 0, and the amount of antibiotic used is reduced.
  • Example 9 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • the marine algae glycoprotein which comprises 8% sugar and 82% protein by weight
  • the molecular weight is 8kDa
  • the marine algae is: chlorella;
  • the sugar is a polysaccharide
  • the polysaccharide comprises: galactose, sialic acid, mannose, arabinose, rhamnose;
  • the protein includes: glutamic acid, lysine, hydroxyproline, threonine, arginine.
  • Example 10 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • Example 11 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • Example 12 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • the marine algal glycoprotein comprises, by weight, 16% sugar, 75% protein,
  • the molecular weight is 20kDa;
  • the marine algae is: spirulina
  • the sugar is a polysaccharide
  • the polysaccharide comprises: galactose, sialic acid, mannose, arabinose, rhamnose;
  • the protein includes: glutamic acid, lysine, hydroxyproline, threonine, arginine.
  • Example 13 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • Example 14 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • compositions of Examples 9-14 of the present invention are for treating influenza, and there are no symptoms of bronchial, pneumonia, and tuberculosis, the total number of complications is 0, and the amount of antibiotic used is reduced.
  • Example 9-11 changing the ratio of marine algae glycoprotein to glucuronic acid, conducting experiments, obtaining Example 10 as a preferred embodiment;
  • Example 12 - Example 14 by changing marine algal glycoprotein, glucuronic acid, The weight ratio of the barley was obtained, and
  • Example 13 was obtained as a preferred embodiment.
  • Example 15 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • weight content including 1 part of marine algae glycoprotein, 6 parts of barley, 7 parts of moxibustion licorice, and 1 part of glucuronic acid.
  • the marine algae glycoprotein comprises, by weight, 25% sugar, 70% protein,
  • the molecular weight is 8kDa
  • the marine algae is: cyanobacteria
  • the sugar is a polysaccharide
  • the polysaccharide comprises: galactose, sialic acid, mannose, arabinose, rhamnose;
  • the protein includes: glutamic acid, lysine, hydroxyproline, threonine, arginine.
  • Embodiment 16 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • the marine algae glycoprotein comprises, by weight, 25% sugar, 70% protein,
  • the molecular weight is 12kDa
  • the marine algae is: cyanobacteria
  • the sugar is a polysaccharide
  • the polysaccharide comprises: galactose, sialic acid, mannose, arabinose, rhamnose;
  • the protein includes: glutamic acid, lysine, hydroxyproline, threonine, arginine.
  • Example 17 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • the marine algae glycoprotein comprises, by weight, 25% sugar, 70% protein,
  • the molecular weight is 60kDa;
  • the marine algae is: cyanobacteria
  • the sugar is a polysaccharide
  • the polysaccharide comprises: galactose, sialic acid, mannose, arabinose, rhamnose;
  • the protein includes: glutamic acid, lysine, hydroxyproline, threonine, arginine.
  • Embodiment 18 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • the marine algae glycoprotein which comprises 45% by weight of sugar and 50% by weight of protein
  • the molecular weight is 200kDa
  • the marine algae is: cyanobacteria
  • the sugar is a polysaccharide
  • the polysaccharide comprises: galactose, sialic acid, mannose, arabinose, rhamnose;
  • the protein includes: glutamic acid, lysine, hydroxyproline, threonine, arginine.
  • Example 19 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • the marine algae glycoprotein which comprises 45% by weight of sugar and 50% by weight of protein
  • the molecular weight is 3000kDa
  • the marine algae is: cyanobacteria
  • the sugar is a polysaccharide
  • the polysaccharide comprises: galactose, sialic acid, mannose, arabinose, rhamnose;
  • the protein includes: glutamic acid, lysine, hydroxyproline, threonine, arginine.
  • Example 20 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • the marine algae glycoprotein which comprises 45% by weight of sugar and 50% by weight of protein
  • the molecular weight is 8kDa
  • the marine algae is: Sargassum;
  • the sugar is a polysaccharide
  • the polysaccharide comprises: galactose, sialic acid, mannose, arabinose, rhamnose;
  • the protein includes: glutamic acid, lysine, hydroxyproline, threonine, arginine.
  • mice were randomly divided into 12 groups according to body weight, and each group was 10, which were normal animal control group, virus infection control group, antiviral oral solution group (1.57 g/kg/d), and the present invention.
  • Each administration group of the present invention was intragastrically administered three times a day, 3 g per day for 4 consecutive days, and the control group was orally administered with distilled water under the same conditions.
  • mice On the fourth day of administration, except for the normal control group, the mice were mildly washed with diethyl ether. Anesthetize, nasally infected with 15 LD 50 influenza virus droplets, each 0.05ml, stop the administration after infection. On the 6th day, the weight of the mice was weighed, dissected, the whole lung was weighed, and the lung index value was calculated. The lung index inhibition rate.
  • Table 8 The preventive effect of the drug of the present invention on mouse influenza virus pneumonia
  • Example 12-14 by changing the weight ratio of marine algae glycoprotein, glucuronic acid, and barley, Example 13 is obtained as a preferred embodiment
  • Example 15-17 by changing the weight ratio of marine algal glycoprotein, barley, moxibustion, glucuronic acid, Example 16 is obtained as a preferred embodiment
  • Example 19 was obtained as a preferred example by changing the weight ratio of marine algal glycoprotein, barley, moxibustion, medlar, and earth.
  • mice were randomly divided into 11 groups according to the body weight, 9 mice in each group, respectively, the virus control group, the antiviral oral solution group (1.57 g/kg/d), the inventive example 12, the inventive example 13, and the present invention.
  • Example 14 Inventive Example 15, Inventive Example 16, Inventive Example 17, Inventive Example 18, Inventive Example 19, and Inventive Example 20.
  • Each administration group of the present invention is administered by intragastric administration 3 times a day, 3 g per day for 3 consecutive days, and the control group is orally administered with distilled water under the same conditions;
  • the animals in each group were intranasally infected with influenza virus, and the amount of infection was 1000 LD 50 , 0.05 ml/head.
  • the mice were sacrificed 48 hours after infection, and the left middle lobe was removed.
  • the pathological sections were routinely dehydrated, embedded, and paraffin sections were prepared. Indirect fluorescent staining was performed to observe the fluorescent particles in the lungs, and the effect of the drug on virus proliferation was observed. More, indicating that the virus particles proliferate more.
  • Example 12-14 by changing the weight ratio of marine algae glycoprotein, glucuronic acid, and barley, Example 13 is obtained as a preferred embodiment
  • Example 15-17 by changing the weight ratio of marine algal glycoprotein, barley, moxibustion, glucuronic acid, Example 16 is obtained as a preferred embodiment
  • Example 19 was obtained as a preferred example by changing the weight ratio of marine algal glycoprotein, barley, moxibustion, medlar, and earth.
  • Example 21 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • composition in parts by weight, comprises the following components:
  • the marine algae glycoprotein in parts by weight, comprises 6% sugar, 85% protein,
  • the sugar in parts by weight, comprises the following components: 13 parts of glucuronic acid, 11 parts of sialic acid, and 15 parts of mannose;
  • the protein in parts by weight, includes the following components: 7 parts of glutamic acid, 10 parts of lysine, and 19 parts of hydroxyproline.
  • the molecular weight is 16kDa
  • the marine algae is: Candida albicans;
  • the cyanobacterium is spirulina, and the spirulina includes 68 g of protein, 300 mg of ⁇ -carotene, 1500 mg of ⁇ -linolenic acid, 4.5 mg of vitamin B1, 5 mg of vitamin B2, 20 mg of vitamin E, and 3.5 mg of spirulina polysaccharide per 100 g of dry powder. , phycocyanin 12g, calcium 400mg, iron 150mg, potassium 2000mg, magnesium 250mg, chlorophyll 2000mg.
  • the perilla young leaf extract is obtained by extracting the young leaves of perilla;
  • the perilla frute leaves 85.7 g per 100 g of water content, 2.4 g protein content, fat content 1.3 g, carbohydrate 6.4 g, phosphorus 44 mg, iron 2.3 mg, carotene 9.09 g, vitamin B10.02 mg, vitamin B20.35 mg, niacin 1.3 mg, vitamin C 47 mg.
  • the licorice extract comprises 30% licorice flavones and 50% glycyrrhetinic acid;
  • Gynostemma pentaphyllum extract Gynostemma pentaphyllum, has a mass percentage of 98%;
  • the perilla leaves After washing and drying the perilla leaves, they are pressed in a press for 10-30 min, then filtered with a 200 mesh filter cloth, the filter residue is discarded, the juice is collected, and the supernatant is centrifuged at 6000 rpm for 15 minutes, and passed through a 0.45 ⁇ m microporous membrane.
  • the original solution of Perilla frutes leaves is obtained, and the stock solution is concentrated, the concentration temperature is 75-90 ° C, the degree of vacuum is -0.05--0.1 MPa, and the filtrate is concentrated to 1/3 to 1/4 of the original volume; then freeze-dried
  • the extract of Perilla frutes leaves is obtained, and the freeze-drying temperature is -20 to -25 ° C, pre-frozen for 6 h to 10 h, the pressure is 155-160 Pa, and the temperature is dried at -50 ° C to obtain a crude extract of Perilla frutes.
  • the thickness of the houttuynia cord is 2-3cm, placed in a hot air circulation oven.
  • the drying temperature is controlled at 65 °C.
  • the moisture content after drying does not exceed the total quality of Houttuynia cordata. 8.5%, naturally let cool to room temperature;
  • the dried Houttuynia cordata was cut into small pieces and then pulverized with a pulverizer to have a particle size of 220 ⁇ m.
  • Houttuynia powder was added, 85% ethanol was added, the mass ratio of Houttuynia powder and 85% ethanol was 1:35, and the mixture was heated and refluxed for 3 hours, filtered, and the dregs were extracted 2 to 5 times in the same manner. The extract is combined, and the dregs are discarded; the extract is recovered to obtain a thick paste, that is, a crude extract of Houttuynia cordata.
  • the elution process is: first eluting 15BV with water, the flow rate is 2BV/h, and then eluting 15BV with 50% ethanol at a flow rate of 3BV/h;
  • the perilla young leaf extract, the licorice extract, the houttuynia cordata extract, and the Gynostemma pentaphyllum extract were dried to a powder state, pulverized to 300 mesh, and marine algae glycoprotein powder was added to prepare different dosage forms.
  • Example 22 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • composition in parts by weight, comprises the following components:
  • the salicylamide has a melting point of 141 ° C and a relative density of 1.286 g / cm 3 ;
  • the Xanthium sibiricum extract has a content of xanthenyl alcohol of 90% by weight;
  • the Luo Han Guo extract the mass percentage of mogroside is 80%;
  • the honeysuckle extract has a chlorogenic acid content of 20% by weight and a moisture content of 9% by weight.
  • the marine algae glycoprotein in parts by weight, comprises 7% sugar, 82% protein,
  • the sugar in parts by weight, comprises the following components: 14 parts of glucuronic acid, 12 parts of sialic acid, and 16 parts of mannose;
  • the protein in parts by weight, includes the following components: 7 parts of glutamic acid, 11 parts of lysine, and 16 parts of hydroxyproline.
  • the molecular weight is 19kDa
  • the marine algae is: kelp;
  • the components were weighed according to the formulation, uniformly mixed, and pulverized to 300 mesh to prepare a composition for treating influenza of the present invention.
  • Example 23 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • composition in parts by weight, comprises the following components:
  • the bearberry extract the mass percentage of ursolic acid is 80%;
  • the alfalfa extract is a pale yellow powder having a barium polysaccharide content of 45%, a moisture content of ⁇ 4%, an ash content of 7%, and a fineness of 100 mesh.
  • the marine algae glycoprotein in parts by weight, comprises 8% sugar, 84% protein,
  • the sugar in parts by weight, comprises the following components: 13 parts of glucuronic acid, 11 parts of sialic acid, and 15 parts of mannose;
  • the protein in parts by weight, includes the following components: 7 parts of glutamic acid, 10 parts of lysine, and 19 parts of hydroxyproline.
  • the molecular weight is 20kDa;
  • the marine algae is: chlorella;
  • the components were weighed according to the formulation, uniformly mixed, and pulverized to 300 mesh to prepare a composition for treating influenza of the present invention.
  • Embodiment 24 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • composition in parts by weight, comprises the following components:
  • the Ginkgo biloba extract has a total flavonoid content of 24-26%, total azlactone content of 8-10%, ginkgolide ⁇ 2.5%, ginkgolide ⁇ 2.0%, ginkgolic acid ⁇ 3ppm, and loss on drying ⁇ 3 %, ignition residue ⁇ 1.5%, solvent residue ⁇ 1;
  • the polysaccharide has a molecular weight of 22-25 kD, including arabinose, glucose, galactose, mannose, xylose, rhamnose, and the mass ratio is 4:5:3:5:2:1;
  • the marine algae glycoprotein in parts by weight, comprises 9% sugar, 76% protein,
  • the sugar in parts by weight, comprises the following components: 13 parts of glucuronic acid, 11 parts of sialic acid, and 15 parts of mannose;
  • the protein in parts by weight, includes the following components: 7 parts of glutamic acid, 10 parts of lysine, and 19 parts of hydroxyproline.
  • the molecular weight is 22kDa
  • the marine algae is: S. algae.
  • the components were weighed according to the formulation, uniformly mixed, and pulverized to 300 mesh to prepare a composition for treating influenza of the present invention.
  • compositions of Examples 21-24 have a stabilizing effect on the body temperature of endotoxin-induced rabbits, and the body temperature increases at 4 hours after the drug. 0.12-0.20 °C.
  • compositions of Examples 21-24 had a significant antipyretic effect on influenza patients, and the antipyretic time after administration was 11.0-12.0 h, and the fever time of the influenza patients in the blank control group was 30.0 h.
  • compositions of Examples 21-24 for cough, sore throat, cough, runny nose, headache, nasal congestion, muscles in influenza patients Soreness and fatigue have obvious relief effects.
  • the time to relieve cough is 1.5-2h
  • the time to relieve sore throat is 1.5-2h
  • the time to relieve cough is 1.1-1.5h
  • the time to relieve runny nose is 0.8-1.2h
  • the time to relieve headache is 0.7-0.85h
  • nasal congestion relief time is 0.8-1h
  • muscle soreness fatigue relief time is 0.9-1h.
  • compositions of Examples 21-24 of the present invention are for treating influenza, and there are no symptoms of bronchial, pneumonia, and tuberculosis, the total number of complications is 0, and the amount of antibiotic used is reduced.
  • Cells African green monkey kidney cells (Vero E6), provided by the Molecular Biology Laboratory of the Institute of Microbiology and Epidemiology, Military Medical Sciences;
  • Virus SARs virus, BJ-01 strain, provided by the Virus Room of the Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences;
  • the virus is measured in the biosafety level three laboratory.
  • Vero E6 cells were seeded in 96-well plates, 100 ⁇ l per well, containing 2 ⁇ 10 4 cells/well, cultured at 37 ° C for 24 h, and the cells were grown into a single layer, and 10 times diluted virus culture solution was added at a concentration of 10 ° C, 37 ° C, 50
  • the cells were cultured in a carbon dioxide incubator, and the cytopathic effect (CPE) was observed with a microscope every day.
  • the concentration of the virus was calculated by Reed-Muench method (TCID 50 ), and the TCID 50 of the virus was determined to be 10 -8 by repeated tests.
  • Vero E6 cells were seeded in a 96-well plate, 100 ⁇ l per well, containing 2 ⁇ 10 4 cells/well, cultured at 37° C. for 24 h, and the cells were grown into a single layer.
  • the drug of Example 3 of the present invention was used, and four concentrations of 1000 were set. 100, 10 and 1 ⁇ g/ml, 4 wells per concentration, 100 ⁇ l of drug solution per well.
  • the test was performed on normal cell controls without drug administration. The cytopathic effect of the drug-administered group was observed every day for 5 days, and the non-toxic concentration of the drug was determined. The results showed that the maximum non-toxic concentration of the drug of the present invention against Vero E6 cells was 100 ⁇ g/ml.
  • Vero E6 cells were seeded in 96-well plates, 100 ⁇ l per well, containing 2 ⁇ 10 4 cells/well, cultured at 37 ° C for 24 h, and the cells were grown into a single layer, 100 ⁇ l of virus (100 TCID 50 ) was added to each well, and after adsorption for 2 hours, Discard the virus, then add the largest non-toxic concentration of the test solution (100 ⁇ g/ml), 100 ⁇ l per well, do 4 duplicate wells (repeated once), and set the virus control and cell control, when the virus control well appears When the lesion is used, the effect of the drug is judged by CPE method (the cytopathic effect is +25%, 26-50% is ++, 51-75% is +++, 76-100% is +++, normal cells are one) . The results are shown in Table 13.
  • 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 26 A medicament for treating influenza, upper respiratory tract infection, viral pneumonia
  • 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: galactose, sialic acid, mannose, arabinose, rhamnose;
  • 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 present invention has obvious therapeutic effects on cytopathic diseases caused by CoxB3, CoxB5, influenza virus, RSV, EHCO11, and HSV-2 viruses, and the therapeutic index is 2.
  • the drug of the present invention has obvious preventive effects on cytopathic diseases caused by CoxB3, CoxB5, influenza virus, Ard-3, Ard-7, RSV and HSV-2 viruses, and the therapeutic index is 2.
  • the drug of the present invention has a certain inhibitory effect on Staphylococcus aureus, pneumococcus, and Pseudomonas aeruginosa, and the titer is 1:2.
  • the drug of the present invention has an antipyretic effect: there is a significant antipyretic effect when administered for 0.5 h.
  • the drug of the present invention has an action against Influenza virus A H1N1 FM STRAIN (commonly referred to as influenza A virus, including H1N1) in vivo.
  • METHODS In vivo assays were conducted to detect the inhibitory effects of 5g/kg and 2.5g/kg of the present invention on pneumonia caused by influenza virus infection in mice and its inhibitory effect on influenza virus infection.
  • RESULTS The drug of the present invention has a significant inhibitory effect on influenza virus in the lungs of mice, and can alleviate inflammatory lesions in the lungs of mice, and has a protective effect on death at a dose of 5 g/kg.
  • the medicament of the present invention has an obvious anti-influenza virus action in vivo.
  • the different dosages of the medicament of the invention have obvious pharmacological effects in the aspects of antiviral, antiviral, antibacterial, anti-inflammatory, antipyretic, analgesic and immune function in vitro.
  • 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流感、上呼吸道感染、病毒性肺炎的药物，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

一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物 技术领域
本发明涉及一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物，属于医药技术领域。
背景技术
流行性感冒(简称流感)是流感病毒引起的急性呼吸道感染，也是一种传染性强、传播速度快的疾病。其主要通过空气中的飞沫、人与人之间的接触或与被污染物品的接触传播。典型的临床症状是：急起高热、全身疼痛、显著乏力和轻度呼吸道症状，一般秋冬季节是其高发期，所引起的并发症和死亡现象非常严重。
流感临床表现的早期症状包括发热、咳嗽、喉痛、身体疼痛、头痛、发热等，有些还会出现腹泻或呕吐、肌肉痛或疲倦、眼睛发红等，部分患者病情可迅速进展，来势凶猛、突然高热、体温超过39℃，甚至继发严重肺炎、急性呼吸窘迫综合症、肺出血、胸腔积液、全血细胞减少、肾功能衰竭、败血症、休克及Reye综合症、呼吸衰竭及多器官损伤，导致死亡，患者原有的基础疾病亦可加重。
目前对流感的患者一般使用抗病毒药物进行治疗，这些药物虽然可减轻疾病的严重程度并提高生存机会，但费用过高并且由于长期使用导致了有些病毒产生耐药性。
专利“Composition of anti-influenza H1N1 virus using ultrafiltration and preparation method thereof”，专利号为：KR101485982(B1)，公开了人参多糖具有免疫活性和抗流感活性；
专利“IMMUNOSTIMULATOR，专利号为JP2014105202(A)公开了提供一种抗流感病毒的抗体，包括多糖，其中糖残基的基本结构包括半乳糖、甘露糖和半乳糖，半乳糖含量优选为50-79％，所述抗体，显著抑制A型流感病毒在肺和呼吸道的作用；
专利“BENZODIAZEPINES AND BENZOTHIAZEPINES DERIVATIVES AND HBSAG PEPTIDES BINDING TO ANNEXINS，THEIR COMPOSITIONS AND USE”，专利号为WO0012547(A2)公开了“一种预防流感病毒感染的鼻滴剂，利用半乳糖醛酸和磷脂、胆固醇、蛋白质、糖蛋白、核酸结合，形成半乳糖醛酸苷，进而有效预防流感病毒。
专利“METHODS AND COMPOSITIONS FOR IMMUNIZATION AGAINST VIRUS”，专利号为US2015335728(A1)公开了一种免疫原性组合物，含有部分糖基化的病毒糖蛋白作为疫苗，对抗流感病毒；
专利“一种盐藻聚糖硫酸酯及其制备方法和在制备抗流感病毒药物中的应用”申请号为：201410132608.X公开了：一种盐藻聚糖硫酸酯，从海带中提取，是以甘露糖和葡萄糖醛酸 为重复单元组成的主链、以岩藻寡聚糖硫酸酯为支链的多糖；
现有的流感治疗药物还存在以下缺陷：
(1)给药后，短时间内，体温得不到控制，体温变化大；
(2)对流感患者的退热效果不明显，投药后退热时间长；
(3)对流感患者的咳嗽、咽痛、咳痰、流鼻涕、头痛、鼻塞、肌肉酸痛、乏力等其他症状的缓解时间较长；
(4)治疗不当，容易引起支气管、肺炎、肺结核等症状，抗生素使用量大。
发明内容
本发明为解决现有技术中存在的不足，提供一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物，以实现以下发明目的：
(1)本发明所述药物，对内毒素致热家兔的体温具有稳定作用，药后4h时，体温变化≤1.10℃；
(2)本发明所述药物，对流感患者有明显的退热效果，投药后退热时间≤20h；
(3)本发明所述药物，对流感患者的咳嗽、咽痛、咳痰、流鼻涕、头痛、鼻塞、肌肉酸痛、乏力具有明显的缓解效果。
(4)本发明所述药物用于治疗流感，无支气管、肺炎、肺结核的症状，无并发症，并且减少抗生素的使用量。
为解决以上技术问题，本发明采用如下技术方案：
一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物，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1-22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1-22份、青黛2-20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6-30份、灸甘草7-13份、葡萄糖醛酸1-15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6-30份、灸甘草7-13份、榧子5-12份、土元4-10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，对内毒素致热家兔的体温具有稳定作用，药后4h时，体温增加0.20-1.10℃。
(2)本发明所述药物，对流感患者有明显的退热效果，投药后退热时间为13.0-20.0h，空白对照组的流感患者的退热时间为30.0h。
(3)本发明所述药物，对流感患者的咳嗽、咽痛、咳痰、流鼻涕、头痛、鼻塞、肌肉酸痛、乏力具有明显的缓解效果，咳嗽缓解时间为2-6h，咽痛缓解时间为2-6h，咳痰缓解时间为1.5-4h，流鼻涕缓解时间为1.2-4h，头痛缓解时间为0.8-7h，鼻塞缓解时间为1-5h，肌肉酸痛、乏力缓解时间为1-4h。
(4)本发明所述药物用于治疗流感，无1例支气管、肺炎、肺结核的症状，并发症总数为0，并且减少抗生素的使用量。
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1一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
所述药物为海洋藻类糖蛋白；
所述海洋藻类糖蛋白，以重量份计，包括糖1％，蛋白质99％，
分子量为0.2kDa；
所述海洋藻类为：蓝藻；
所述糖，为多糖；
所述多糖，包括：半乳糖、唾液酸、甘露糖、阿拉伯糖、鼠李糖；
所述蛋白质，包括：谷氨酸、赖氨酸、羟脯氨酸、苏氨酸、精氨酸；
实施例2一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
所述药物为海洋藻类糖蛋白；
所述海洋藻类糖蛋白，以重量份计，包括糖6％，蛋白质85％，
分子量为16kDa；
所述海洋藻类为：绿藻；
所述糖，为多糖；
所述多糖，包括：半乳糖、唾液酸、甘露糖、阿拉伯糖、鼠李糖；
所述蛋白质，包括：谷氨酸、赖氨酸、羟脯氨酸、苏氨酸、精氨酸；
实施例3一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
所述药物为海洋藻类糖蛋白；
所述海洋藻类糖蛋白，以重量份计，包括糖15％，蛋白质74％，
分子量为3kDa；
所述海洋藻类为：蓝藻；
所述糖，为多糖；
所述多糖，包括：半乳糖、唾液酸、甘露糖、阿拉伯糖、鼠李糖；
所述蛋白质，包括：谷氨酸、赖氨酸、羟脯氨酸、苏氨酸、精氨酸；
实施例4一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
所述药物为海洋藻类糖蛋白；
所述海洋藻类糖蛋白，以重量份计，包括糖32％，蛋白质60％，
分子量为120kDa；
所述海洋藻类为：红藻；
所述糖，为多糖；
所述多糖，包括：半乳糖、唾液酸、甘露糖、阿拉伯糖、鼠李糖；
所述蛋白质，包括：谷氨酸、赖氨酸、羟脯氨酸、苏氨酸、精氨酸；
实施例5一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
所述药物为海洋藻类糖蛋白；
所述海洋藻类糖蛋白，以重量份计，包括糖75％，蛋白质20％
分子量为600kDa；
所述海洋藻类为：褐藻；
所述糖，为多糖；
所述多糖，包括：半乳糖、唾液酸、甘露糖、阿拉伯糖、鼠李糖；
所述蛋白质，包括：谷氨酸、赖氨酸、羟脯氨酸、苏氨酸、精氨酸；
实施例6一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
所述药物为海洋藻类糖蛋白；
所述海洋藻类糖蛋白，以重量份计，包括糖99％、蛋白质1％；
分子量为3000kDa；
所述海洋藻类为：金藻；
所述糖，为多糖；
所述多糖，包括：半乳糖、唾液酸、甘露糖、阿拉伯糖、鼠李糖；
所述蛋白质，包括：谷氨酸、赖氨酸、羟脯氨酸、苏氨酸、精氨酸。
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：
一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
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，为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程胶囊、片剂等。
实施例7本发明药物对内毒素致发热家兔体温的影响
(1)剂量试验
a、本发明实施例2所述药物，剂量为0.4g/日、0.8g/日、1g/日、2g/日、4g/日、8g/日，一天3次灌胃给药；
b、阳性对照药阿司匹林泡腾片，阿斯利康制药有限公司生产，批号为080217，临床用量1片/日(每片含0.5g)，按60公斤体重计算为0.017片/kg，试验选用临床等效剂量，家兔用1g/天，一日三次。
c、动物家兔，1.5-2.0kg，雌雄各半；
d、内毒素大肠杆菌内毒素，Sigma产品；
e、仪器7151型半导体温度计；
试验方法：
按陈奇主编的《中药药理研究方法学》(人民卫生出版社，北京，1993年)第244页的方法检测本发明药物对内毒素致发热家兔体温的影响
取健康家兔称体重，试验当日测正常肛门温度2次，选肛温在38.5-39.5℃及两次温度相差0.4℃以内的动物供试验用，每组10只家兔；
以140ng/ml/kg的大肠杆菌内毒素由家兔耳静脉注射，1小时后，测肛温升高值，按升高值调整分组后分别灌胃给予相应药物。模型对照组灌胃同体积的蒸馏水。药后1、2、3、4小时各测肛温一次，以不同时间所测肛温与基础肛温之差值，为体温变化值。
表1不同剂量的本发明药物对内毒素致热家兔体温的影响
Figure PCTCN2017071874-appb-000001
本发明实施例2所述药物，在0.4-8g/日的剂量下，对内毒素引起家兔的体温升高均有一定的抑制效果，优选剂量为1-4g/日，更优选的为2-4g/日，最优选的为3g/日。
(2)本发明实施例1-6所述药物对内毒素致热家兔体温的影响
表2本发明药物对内毒素致热家兔体温的影响
Figure PCTCN2017071874-appb-000002
实施例1-6所述药物，对内毒素致热家兔的体温具有稳定作用，药后4h时，体温增加0.20-1.10℃，实施例2、实施例3是优选实施例。
实施例8所述药物在治疗流感中的应用
(1)患者的选择条件：
筛查394名流感患者，所有患者均符合以下条件：符合卫生部制定的诊断标准；14-70岁；发病时间(出现发热，腋下体温≥37.5℃伴咽痛、咳嗽症状)≤72小时；症状：发烧≤39.5℃、咳嗽、咽痛、头痛、流鼻涕、鼻塞、咳痰。
排除标准：妊娠；肺炎；严重基础病；免疫缺陷；入组前服用抗病毒药；有脏器功能衰竭。
(2)组别：
分别设置空白对照组、本发明所述糖蛋白治疗组(实施例5)，服用药物剂量为3g/日，一天服用三次。
(3)主要观察指标评估，见表3；
表3投药-退热时间情况
Figure PCTCN2017071874-appb-000003
实施例1-6所述药物，对流感患者有明显的退热效果，投药后退热时间为13.0-20.0h，空白对照组的流感患者的退热时间为30.0h。实施例2和实施例3是优选实施例。
(4)次要观察指标，见表4：
表4投药-缓解时间
Figure PCTCN2017071874-appb-000004
实施例1-6所述的药物，对流感患者的咳嗽、咽痛、咳痰、流鼻涕、头痛、鼻塞、肌肉酸痛、乏力具有明显的缓解效果，咳嗽缓解时间为2-6h，咽痛缓解时间为2-6h，咳痰缓解时间为1.5-4h，流鼻涕缓解时间为1.2-4h，头痛缓解时间为0.8-7h，鼻塞缓解时间为1-5h，肌肉酸痛、乏力缓解时间为1-4h。实施例2和实施例3是优选实施例。
(5)并发症、合并症、抗生素：
本发明所述糖蛋白用于治疗流感，无1例支气管、肺炎、肺结核的症状，并发症总数为0，并且减少抗生素的使用量。
实施例9一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
以重量份计，包括海洋藻类糖蛋白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8％，蛋白质82％，
分子量为8kDa；
所述海洋藻类为：小球藻；
所述糖，为多糖；
所述多糖，包括：半乳糖、唾液酸、甘露糖、阿拉伯糖、鼠李糖；
所述蛋白质，包括：谷氨酸、赖氨酸、羟脯氨酸、苏氨酸、精氨酸。
实施例10一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
同实施例9，只改变海洋藻类糖蛋白和葡萄糖醛酸的配比，改变为：
以重量份计，包括海洋藻类糖蛋白42份、葡萄糖醛酸14份。
实施例11一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
同实施例9，只改变海洋藻类糖蛋白和葡萄糖醛酸的配比，改变为：
以重量份计，包括海洋藻类糖蛋白99份、葡萄糖醛酸22份。
实施例12一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
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2份。
所述海洋藻类糖蛋白，以重量含量计，包括糖16％，蛋白质75％，
分子量为20kDa；
所述海洋藻类为：螺旋藻；
所述糖，为多糖；
所述多糖，包括：半乳糖、唾液酸、甘露糖、阿拉伯糖、鼠李糖；
所述蛋白质，包括：谷氨酸、赖氨酸、羟脯氨酸、苏氨酸、精氨酸。
实施例13一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
同实施例12，只改变海洋藻类糖蛋白、葡萄糖醛酸、青黛的配比，改变为：
以重量含量计，包括海洋藻类糖蛋白39份、葡萄糖醛酸16份、青黛11份。
实施例14一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
同实施例12，只改变海洋藻类糖蛋白、葡萄糖醛酸、青黛的配比，改变为：
以重量含量计，包括海洋藻类糖蛋白99份、葡萄糖醛酸22份、青黛20份。
采取实施例7、8所述实验方法，采用实施例9-14所制备的治疗流感的组合物，进行实验，结果为：
(1)本发明药物对内毒素致热家兔体温的影响
表5对内毒素致热家兔体温的影响
Figure PCTCN2017071874-appb-000005
(2)本发明药物对投药-退热时间的影响
表6投药-退热时间情况
Figure PCTCN2017071874-appb-000006
(3)本发明药物对投药-缓解时间的影响
表7投药-缓解时间
Figure PCTCN2017071874-appb-000007
(5)并发症、合并症、抗生素：
本发明实施例9-14所述组合物，用于治疗流感，无1例支气管、肺炎、肺结核的症状，并发症总数为0，并且减少抗生素的使用量。
实施例9-11，改变海洋藻类糖蛋白和葡萄糖醛酸的配比，进行实验，得到实施例10为优选实施例；实施例12-实施例14，通过改变海洋藻类糖蛋白、葡萄糖醛酸、青黛的重量配比，得到实施例13为优选实施例。
实施例15一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
以重量含量计，包括海洋藻类糖蛋白1份、青黛6份、灸甘草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25％，蛋白质70％，
分子量为8kDa；
所述海洋藻类为：蓝藻；
所述糖，为多糖；
所述多糖，包括：半乳糖、唾液酸、甘露糖、阿拉伯糖、鼠李糖；
所述蛋白质，包括：谷氨酸、赖氨酸、羟脯氨酸、苏氨酸、精氨酸。
实施例16一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
以重量含量计，包括海洋藻类糖蛋白53份、青黛19份、灸甘草11份、葡萄糖醛酸9份。
所述海洋藻类糖蛋白，以重量含量计，包括糖25％，蛋白质70％，
分子量为12kDa；
所述海洋藻类为：蓝藻；
所述糖，为多糖；
所述多糖，包括：半乳糖、唾液酸、甘露糖、阿拉伯糖、鼠李糖；
所述蛋白质，包括：谷氨酸、赖氨酸、羟脯氨酸、苏氨酸、精氨酸。
实施例17一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
以重量含量计，包括海洋藻类糖蛋白99份、青黛30份、灸甘草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25％，蛋白质70％，
分子量为60kDa；
所述海洋藻类为：蓝藻；
所述糖，为多糖；
所述多糖，包括：半乳糖、唾液酸、甘露糖、阿拉伯糖、鼠李糖；
所述蛋白质，包括：谷氨酸、赖氨酸、羟脯氨酸、苏氨酸、精氨酸。
实施例18一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
以重量含量计，包括海洋藻类糖蛋白1份、青黛6份、灸甘草7份、榧子5份、土元4份。
所述海洋藻类糖蛋白，以重量含量计，包括糖45％，蛋白质50％，
分子量为200kDa；
所述海洋藻类为：蓝藻；
所述糖，为多糖；
所述多糖，包括：半乳糖、唾液酸、甘露糖、阿拉伯糖、鼠李糖；
所述蛋白质，包括：谷氨酸、赖氨酸、羟脯氨酸、苏氨酸、精氨酸。
实施例19一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
以重量含量计，包括海洋藻类糖蛋白44份、青黛22份、灸甘草9份、榧子7份、土元5份。
所述海洋藻类糖蛋白，以重量含量计，包括糖45％，蛋白质50％，
分子量为3000kDa；
所述海洋藻类为：蓝藻；
所述糖，为多糖；
所述多糖，包括：半乳糖、唾液酸、甘露糖、阿拉伯糖、鼠李糖；
所述蛋白质，包括：谷氨酸、赖氨酸、羟脯氨酸、苏氨酸、精氨酸。
实施例20一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
以重量含量计，包括海洋藻类糖蛋白99份、青黛30份、灸甘草13份、榧子12份、土元10份。
所述海洋藻类糖蛋白，以重量含量计，包括糖45％，蛋白质50％，
分子量为8kDa；
所述海洋藻类为：马尾藻；
所述糖，为多糖；
所述多糖，包括：半乳糖、唾液酸、甘露糖、阿拉伯糖、鼠李糖；
所述蛋白质，包括：谷氨酸、赖氨酸、羟脯氨酸、苏氨酸、精氨酸。
上述实施例12-20在治疗流感中的应用试验：
(1)本发明实施例12-20药物对小鼠流感病毒性肺炎的预防作用
取小鼠，按体重随机分成12组，每组10只，分别为正常动物对照组、病毒感染对照组、抗病毒口服液组(1.57g/kg/d)、本发明实施例12、本发明实施例13、本发明实施例14、本发明实施例15、本发明实施例16、本发明实施例17、本发明实施例18、本发明实施例19、本发明实施例20。本发明各给药组灌胃给药，每天3次，每天3g，连续4天，对照组在同等条件下蒸馏水灌胃，给药第4天除正常对照组外，将小鼠用乙醚轻度麻醉，以15个LD50流感病毒液滴鼻感染，每只0.05ml，感染后停止给药，第6天称取小鼠体重后解剖，摘取全肺称重，计算肺指数值，并求出肺指数抑制率。
表8本发明药物对小鼠流感病毒性肺炎的预防作用；
Figure PCTCN2017071874-appb-000008
实施例12-14，通过改变海洋藻类糖蛋白、葡萄糖醛酸、青黛的重量配比，得到实施例13为优选实施例；
实施例15-17，通过改变海洋藻类糖蛋白、青黛、灸甘草、葡萄糖醛酸的重量配比，得到实施例16为优选实施例；
实施例18-20，通过改变海洋藻类糖蛋白、青黛、灸甘草、榧子、土元的重量配比，得到实施例19为优选实施例。
(2)本发明实施例12-20所述药物对小鼠肺内流感病毒增值量的影响
取小鼠，按体重随机分成11组，每组9只，分别病毒对照组、抗病毒口服液组(1.57g/kg/d)、本发明实施例12、本发明实施例13、本发明实施例14、本发明实施例15、本发明实施例16、本发明实施例17、本发明实施例18、本发明实施例19、本发明实施例20。本发明各给药组灌胃给药，每天3次，每天3g，连续3天，对照组在同等条件下蒸馏水灌胃；
与给药第2天各组动物滴鼻感染流感病毒，感染量为1000LD50，0.05ml/只。感染病毒后48小时处死小鼠，摘取左肺中叶固定，按病理切片常规脱水、包埋、制作石蜡切片，间接荧光染色，观察肺内荧光颗粒，判断药物对病毒增值的作用，荧光阳性数多，表明病毒颗粒增殖 多。
表9本发明药物对小鼠肺内流感病毒增殖量的影响
Figure PCTCN2017071874-appb-000009
实施例12-14，通过改变海洋藻类糖蛋白、葡萄糖醛酸、青黛的重量配比，得到实施例13为优选实施例；
实施例15-17，通过改变海洋藻类糖蛋白、青黛、灸甘草、葡萄糖醛酸的重量配比，得到实施例16为优选实施例；
实施例18-20，通过改变海洋藻类糖蛋白、青黛、灸甘草、榧子、土元的重量配比，得到实施例19为优选实施例。
实施例21一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
所述组合物，以重量份计，包括以下组分：
海洋藻类糖蛋白70份、紫苏嫩叶提取物10份、甘草提取物5份、鱼腥草提取物6份、绞股蓝提取物3份。
所述海洋藻类糖蛋白，以重量份计，包括糖6％，蛋白质85％，
所述糖，以重量份计，包括如下组分：葡萄糖醛酸13份，唾液酸11份，甘露糖15份；
所述蛋白质，以重量份，包括如下组分：谷氨酸7份、赖氨酸10份、羟脯氨酸19份。
分子量为16kDa；
所述海洋藻类为：念珠藻；
所述蓝藻为螺旋藻，所述螺旋藻，每100g干粉中包括蛋白质68g，β-胡萝卜素300mg，γ-亚麻酸1500mg，维生素B1 4.5mg，维生素B2 5mg，维生素E 20mg，螺旋藻多糖3.5mg，藻蓝蛋白12g，钙400mg，铁150mg，钾2000mg，镁250mg，叶绿素2000mg。
所述紫苏嫩叶提取物，由紫苏嫩叶提取得到；
所述紫苏嫩叶，每100g含水分85.7g，蛋白质含量2.4g，脂肪含量为1.3g，碳水化合物6.4克，磷44毫克，铁2.3毫克，胡萝卜素9.09克，维生素B10.02毫克，维生素B20.35毫克，尼克酸1.3毫克，维生素C 47毫克。
所述甘草提取物，包括甘草黄酮30％，甘草次酸50％；
所述绞股蓝提取物，绞股蓝甙的质量百分含量为98％；
所述治疗流感的药物的制备方法：
(1)制备紫苏嫩叶粗提取物
将紫苏嫩叶经清洗干燥后，在压榨机中压榨10-30min，然后用200目滤布过滤，弃去滤渣，收集汁液，6000rpm，15min离心得上清液，经0.45μm微孔滤膜过滤后，得到紫苏嫩叶原液，将原液浓缩，浓缩温度为75～90℃，真空度为-0.05～-0.1MPa，滤液浓缩至原体积的1/3～1/4；然后经冷冻干燥，制得紫苏嫩叶提取物，所述冷冻干燥温度-20～-25℃，预冻6h～10h，压强155-160Pa，温度-50℃干燥，得到紫苏嫩叶粗提取物。
(2)制备鱼腥草提取物
a、清洗
b、干燥、粉碎
将清洗干净的鱼腥草放于干燥盘中，盘中鱼腥草的厚度为2-3cm，置于热风循环烘箱中，干燥温度控制在65℃，干燥后水分含量不超过鱼腥草总质量的8.5％，自然放凉至室温；
干燥后的鱼腥草，切成小段，然后用粉碎机粉碎，粒径为220μm。
c、加热回流提取
取鱼腥草粉末，加入85％的乙醇，鱼腥草粉末和85％的乙醇的质量比例为1∶35，加热回流提取3小时，过滤，药渣以同样的方法先后提取2～5次，合并提取液，药渣弃去；提取液回收乙醇，得稠膏，即鱼腥草粗提取物。
d、大孔吸附树脂柱洗脱提纯
取鱼腥草粗提取物，加入12倍体积份的水稀释，上D101型大孔吸附树脂柱，树脂量为鱼 腥草粗提取物的13倍体积份，径高比为1∶8，吸附流速2.0BV/h；
洗脱过程为：先用水洗脱15BV，流速2BV/h，再用50％的乙醇洗脱15BV，流速3BV/h；
最后用70％的乙醇洗脱14BV，流速1.5BV/h，收集70％乙醇洗脱液，回收溶剂，剩余提取物进行干燥，得鱼腥草粗提取物。
(3)干燥
将紫苏嫩叶提取物、甘草提取物、鱼腥草提取物、绞股蓝提取物干燥成粉末状态，粉碎至300目，加入海洋藻类糖蛋白粉末，制成不同的剂型。
实施例22一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
所述组合物，以重量份计，包括以下组分：
海洋藻类糖蛋白75份、罗汉果提取物12份、金银花提取物6份、苍耳子提取物8份、水杨酰胺2份；
所述水杨酰胺，熔点为141℃、相对密度为1.286g/cm3；
所述苍耳子提取物，异苍耳醇的含量为90wt％；
所述罗汉果提取物，罗汉果甜苷的质量百分含量为80％；
所述金银花提取物，绿原酸含量为20wt％，水分含量为9wt％。
所述海洋藻类糖蛋白，以重量份计，包括糖7％，蛋白质82％，
所述糖，以重量份计，包括如下组分：葡萄糖醛酸14份，唾液酸12份，甘露糖16份；
所述蛋白质，以重量份，包括如下组分：谷氨酸7份、赖氨酸11份、羟脯氨酸16份。
分子量为19kDa；
所述海洋藻类为：海带；
按配方称取各组分，混合均匀，粉碎至300目，制得本发明用于治疗流感的组合物。
实施例23一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
所述组合物，以重量份计，包括以下组分：
海洋藻类糖蛋白78份、熊果提取物8份、白藜芦醇7份、茯苓提取物6份、三叶甙4份；
所述熊果提取物，熊果酸的质量百分含量为80％；
所述茯苓提取物，为浅黄色粉末，茯苓多糖含量为45％，水分＜4％，灰分＜7％，细度100目。
所述海洋藻类糖蛋白，以重量份计，包括糖8％，蛋白质84％，
所述糖，以重量份计，包括如下组分：葡萄糖醛酸13份，唾液酸11份，甘露糖15份；
所述蛋白质，以重量份，包括如下组分：谷氨酸7份、赖氨酸10份、羟脯氨酸19份。
分子量为20kDa；
所述海洋藻类为：小球藻；
按配方称取各组分，混合均匀，粉碎至300目，制得本发明用于治疗流感的组合物。
实施例24一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
所述组合物，以重量份计，包括以下组分：
海洋藻类糖蛋白75份、芦根8份、银杏叶提取物9份、枸杞多糖6份、荷叶碱2份、芹菜素3份、紫杉醇5份；
所述银杏叶提取物，总黄酮甙含量为24-26％，总萜内酯含量8-10％，白果内酯≥2.5％，银杏内酯≥2.0％，银杏酸≤3ppm，干燥失重≤3％，炽灼残渣≤1.5％，溶济残留≤1；
所述枸杞多糖，分子量为22～25kD，包括阿拉伯糖、葡萄糖、半乳糖、甘露糖、木糖、鼠李糖，质量比例为4∶5∶3∶5∶2∶1；
所述海洋藻类糖蛋白，以重量份计，包括糖9％，蛋白质76％，
所述糖，以重量份计，包括如下组分：葡萄糖醛酸13份，唾液酸11份，甘露糖15份；
所述蛋白质，以重量份，包括如下组分：谷氨酸7份、赖氨酸10份、羟脯氨酸19份。
分子量为22kDa；
所述海洋藻类为：珊藻。
按配方称取各组分，混合均匀，粉碎至300目，制得本发明用于治疗流感的组合物。
采取实施例7、8所述实验方法，采用实施例22-24所制备的治疗流感的组合物，进行实验，结果为：
(1)本发明药物对内毒素致热家兔体温的影响
表10对内毒素致热家兔体温的影响
Figure PCTCN2017071874-appb-000010
实施例21-24所述组合物，对内毒素致热家兔的体温具有稳定作用，药后4h时，体温增加 0.12-0.20℃。
(2)本发明药物对投药-退热时间的影响
表11投药-退热时间情况
Figure PCTCN2017071874-appb-000011
实施例21-24所述组合物，对流感患者有明显的退热效果，投药后退热时间为11.0-12.0h，空白对照组的流感患者的退热时间为30.0h。
(3)本发明药物对投药-缓解时间的影响
表12投药-缓解时间
Figure PCTCN2017071874-appb-000012
实施例21-24所述的组合物，对流感患者的咳嗽、咽痛、咳痰、流鼻涕、头痛、鼻塞、肌肉 酸痛、乏力具有明显的缓解效果，咳嗽缓解时间为1.5-2h，咽痛缓解时间为1.5-2h，咳痰缓解时间为1.1-1.5h，流鼻涕缓解时间为0.8-1.2h，头痛缓解时间为0.7-0.85h，鼻塞缓解时间为0.8-1h，肌肉酸痛、乏力缓解时间为0.9-1h。
(5)并发症、合并症、抗生素：
本发明实施例21-24所述组合物，用于治疗流感，无1例支气管、肺炎、肺结核的症状，并发症总数为0，并且减少抗生素的使用量。
实施例25本发明药物对体外抗SARS病毒初筛试验
一、试验材料：
1、细胞：非洲绿猴肾细胞(Vero E6)，由军事医学科学微生物流行病研究所分子生物学研究室提供；
2、病毒：SARs病毒，BJ-01株，由军事医学科学院微生物流行病研究所病毒室提供；
3、培养基：DMEM培养基加10％小牛血清；
4、样品及来源：本发明实施例3所述药物
二、实验的基本条件：病毒测定在生物安全三级实验室。
三、病毒毒力测定：
Vero E6细胞接种于96孔板，每孔100μl，含细胞2×104个/孔，37℃培养24h，细胞长成单层，加入10倍稀释9个浓度的病毒培养液，37℃，50％二氧化碳温箱培养，每天用显微镜观察细胞病变(CPE)，每浓度4孔，用Reed-Muench法计算病毒半数感染剂量(TCID50)，经重复试验确定该病毒的TCID50是10-8。
四、药物对细胞毒性的测定
Vero E6细胞接种于96孔板，每孔100μl，含细胞2×104个/孔，37℃培养24h，细胞长成单层，采用本发明实施例3所述药物，设置4个浓度1000、100、10和1μg/ml，每浓度4孔，每孔加100μl药液。试验设不加药的正常细胞对照。每天观察给药组细胞病变，连续观察5天，确定药物的无毒浓度，结果表明，本发明药物对Vero E6细胞的最大无毒浓度为100μg/ml。
五、抗病毒药效测定：
Vero E6细胞接种于96孔板，每孔100μl，含细胞2×104个/孔，37℃培养24h，细胞长成单层，每孔加100μl病毒(100 TCID50)，吸附2小时后，弃去病毒，然后加入最大无毒浓度的待测药液(100μg/ml)，每孔100μl，做4个复孔(实验重复一次)，同时设病毒对照和细胞对照，当病毒对照孔出现明显病变时，用CPE法判断药效(细胞病变在25％以下 为+，26-50％为++，51-75％为+++，76-100％为+++，正常细胞为一)。结果见表13。
表13本发明药物对SARS病毒的作用
Figure PCTCN2017071874-appb-000013
感染病毒量100 TCID50
采用实施例25所述实验方法，对本发明其他实施例的药物进行实验，结果见表14。
表14本发明药物对SARS病毒的作用
Figure PCTCN2017071874-appb-000014
感染病毒量100 TCID50
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26一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
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：半乳糖、唾液酸、甘露糖、阿拉伯糖、鼠李糖；
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。
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。
本发明药物还有以下效果：
(1)本发明所述药物对CoxB3、CoxB5、流感病毒、RSV、EHCO11、HSV-2病毒所致细胞病变有明显的治疗作用，治疗指数均为2。
(2)本发明所述药物对CoxB3、CoxB5、流感病毒、Ard-3、Ard-7、RSV、HSV-2病毒所致细胞病变有明显的预防作用，治疗指数均为2。
(3)本发明所述药物对金色葡萄球菌、肺炎球菌、绿脓杆菌有一定抑制作用，效价为1∶2。
(4)本发明所述药物具有解热作用：给药0.5h有明显解热作用。
(5)本发明所述药物具有体内抗甲1型流感病毒FMI株(Influenza virus A H1N1 FM STRAIN)(通常称甲型流感病毒，包括H1N1)作用。方法：体内试验检测本发明药物5g/kg和2.5g/kg对小鼠感染流感病毒所致肺炎的抑制作用和死亡保护探讨其对感染流感病毒的抑制作用。结果：本发明药物对小鼠肺内的流感病毒有明显抑制作用，能减轻小鼠肺内的炎性病变，在剂量为5g/kg时对小鼠有死亡保护作用。本发明药物在体内具有明显的抗流感病毒作用。
本发明药物不同剂量在体外抗病毒、体内抗病毒、抑菌、抗炎、解热、镇痛、提高免疫功能七个方面，有明显的药理作用。
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. 一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物，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流感、上呼吸道感染、病毒性肺炎的药物，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流感、上呼吸道感染、病毒性肺炎的药物，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流感、上呼吸道感染、病毒性肺炎的药物，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流感、上呼吸道感染、病毒性肺炎的药物，其特征在于：以重量含量计，包括糖蛋白1-99份、葡萄糖醛酸1-22份。
  6. 根据权利要求1所述的一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物，其特征在于：以重量含量计，包括糖蛋白1-99份、葡萄糖醛酸1-22份、青黛2-20份。
  7. 根据权利要求1所述的一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物，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流感、上呼吸道感染、病毒性肺炎的药物，其特征在于：以重量含量计，包括糖蛋白1-99份、青黛6-30份、灸甘草7-13份、葡萄糖醛酸1-15份。
  9. 根据权利要求1所述的一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物，其特征在于：以重量含量计，包括糖蛋白1-99份、青黛6-30份、灸甘草7-13份、榧子5-12份、土元4-10份。
  10. 根据权利要求5-9任一项所述的一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物，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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