WO2007101370A1 - Utilisation d'un glycoconjugué chb pour préparer un médicament destiné à la prophylaxie ou au traitement de la grippe ou de la grippe aviaire - Google Patents

Utilisation d'un glycoconjugué chb pour préparer un médicament destiné à la prophylaxie ou au traitement de la grippe ou de la grippe aviaire Download PDF

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Publication number
WO2007101370A1
WO2007101370A1 PCT/CN2006/000433 CN2006000433W WO2007101370A1 WO 2007101370 A1 WO2007101370 A1 WO 2007101370A1 CN 2006000433 W CN2006000433 W CN 2006000433W WO 2007101370 A1 WO2007101370 A1 WO 2007101370A1
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WO
WIPO (PCT)
Prior art keywords
chb
glycoconjugate
influenza
virus
subtype
Prior art date
Application number
PCT/CN2006/000433
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English (en)
Chinese (zh)
Inventor
Zhida Wu
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Zhida Wu
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Publication date
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Publication of WO2007101370A1 publication Critical patent/WO2007101370A1/fr

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    • 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
    • A61K35/56—Materials from animals other than mammals
    • A61K35/58—Reptiles
    • A61K35/583—Snakes; Lizards, e.g. chameleons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses

Definitions

  • glycoconjugate CHB in preparing medicine for preventing influenza or bird flu
  • the invention belongs to the field of pharmacy and relates to the use of the glycoconjugate CHB in the preparation of a medicament for controlling influenza or avian influenza. Background technique
  • glycoconjugate CHB is a polysaccharide compound which is isolated and extracted from the serum of sputum or / and turtle.
  • the patent document published as CN1566151, entitled “Glycoconjugate CHB extracted with serum of sputum or / and turtle, and preparation process and its use in pharmaceutical preparation” discloses the extraction method and physical and chemical properties of CHB:
  • This product is white or off-white powdery solid, odorless, soluble in water, and the pH of the aqueous solution is 6.5 ⁇ 7.0.
  • the neutral sugar content is 5 ⁇ 10%.
  • the glycoconjugate CHB contains 18 kinds of amino acids (tryptophan is not measured), and the content ratio of various amino acids is shown in Table 1:
  • Ultraviolet spectrum In addition to strong absorption of -OH in the far ultraviolet region, there is a distinct protein absorption peak around 275 mm.
  • High performance liquid chromatography (HPLC) behavior The column is TSK-G2000SW, the mobile phase is water, and the flow rate is 1.0ml/min. There is an absorption peak around 14.0 min, and the content is 80-90%.
  • CHB has a strong immunological activity and regulates hematopoietic function, and can be used for the preparation of a medicament for treating or preventing an immune-related disease, a hematopoietic system-related disease, a liver disease, and an anti-tumor.
  • type A has the strongest attack power because the type A virus is densely covered with two proteins, namely hemagglutinin (H) and neuraminidase (N), after the virus infects the organism. They can proliferate quickly. Among them, H has 15 subtypes and N has 9 subtypes. The combination of the two is different, and the toxicity and speed of transmission of the virus are also different. In theory, there are 135 types of type A viruses.
  • antibodies can be produced in the body.
  • the antibodies prevent the virus from moving and protect the body from harm.
  • the role Most people with flu can heal themselves after a fever, soreness, sweating, etc., but some patients will deteriorate due to poor self-immunity. As a result, approximately 10,000 people die from the flu during each flu season.
  • a wide variety of A viruses can be transmitted from wild animals to livestock and poultry, and widely spread in chickens, ducks, and pigs. If the virus carried by these livestock and poultry is genetically modified, the ability to transmit in the human population can cause great harm to humans.
  • avian influenza virus H5 has been a new face in type A, mainly in chickens, ducks, geese, and pigeons.
  • avian influenza can be divided into three categories: highly pathogenic, low pathogenic and non-pathogenic. Highly pathogenic avian influenza is classified as a Class A animal disease by the World Organisation for Animal Health because of its rapid spread and great harm. China has classified it as a class of animal diseases.
  • H5N 1 infected poultry and their feces or direct contact with H5N 1 virus will be infected, and even human cases of H5N1 avian influenza virus death, and once the virus mutates in humans, it is possible to obtain The ability to transmit in the crowd.
  • H7 and H9 viruses have also discovered.
  • Avian influenza is a high-mortality contact viral infection and is a zoonotic disease that is extremely harmful.
  • the World Health Organization says that bird flu is a very dangerous virus that could lead to a global crisis.
  • bird flu in some countries has caused a severe blow to the economy of these countries and caused many people to die from the disease.
  • immunoprophylaxis is very important. It is usually immunized with avian influenza virus (AIV) oil emulsion, but AIV antigen.
  • AIV avian influenza virus
  • the object of the present invention is to provide a use of the glycoconjugate CHB for the preparation of a medicament for controlling influenza or avian influenza in response to the above problems.
  • the method and physicochemical properties of the prepared glycoconjugate CHB were studied experimentally. It was found that the glycoconjugate CHB inhibited the H1N1, H3N2 and H5N1 subtype influenza viruses, and the glycoconjugate CHB was prepared to prevent influenza or Application in avian flu drugs.
  • glycoconjugate CHB provided by the invention in the preparation of a medicament for preventing influenza or avian influenza can relieve the lack of avian influenza control drugs on the one hand, and on the other hand, the sugar conjugate CHB is a natural substance extracted, and the side effect is small. And the glycoconjugate CHB can achieve immune control against a variety of influenza or avian influenza virus subtypes by improving the body's immunity, thereby exerting a control effect on various influenza or avian influenza virus subtypes (experimental data see effect examples). detailed description
  • the chemical structure of the glycoconjugate CHB consists of a neutral sugar and 18 amino acids, and has strong immunological activity.
  • the immunological activity of the glycoconjugate CHB was used to study its clearance and inhibition of influenza virus.
  • Test drug CHB oral solution, 30mL / bottle, CHB content is 1.5mg / ml, provided by Shanghai Ningkang Biological Co., Ltd. (according to the content of the preparation example, that is, according to the public nickname CN1566151, the name is ""
  • the sugar conjugate CHB extracted with sputum or/and the serum of the turtle and the preparation process and its application in pharmacy are prepared as disclosed in the patent literature.
  • Test animals SPF grade BALB/C mice were purchased from Beijing Weitong Lihua Experimental Animal Co., Ltd.
  • virus strain influenza virus, influenza virus A/swine/Guangdong/716/03 (mNl subtype) isolated from animals provided by the Key Laboratory of Animal Influenza of the Ministry of Agriculture, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences; A/ Swine/Guangdong/08/03 (H3N2 subtype); A/swine/Fujian/l/03 (H5N1 subtype) strain.
  • the virus was cryopreserved at 70 °C, inoculated with 10 days old SPF chicken embryos, and cultured in a 35-inch incubator.
  • the virus solution was harvested, stored in a cryotube, and stored at 70 ° C. Place on ice and slowly melt.
  • mice were anesthetized with a dry ice prior to inoculation.
  • mice were sacrificed on the 5th day after inoculation, and the lungs were aseptically removed, ground in a mortar, and then made into a 20% suspension. After centrifugation at 3000 rpm/min for 10 minutes, the supernatant was inoculated with SPF chicken embryos, 0.1 ml/embryo.
  • the allantoic fluid was taken one by one for hemagglutination HA test, and the HA test (+) was judged to be chicken embryo infection.
  • the half-infected dose (MID50) of the obtained strain to the mouse was calculated by the REED-MUENCH method.
  • mice were used as experimental animal models. Each virus subtype was randomly divided into 11 groups, 10 rats/group, and the mice were challenged with different doses of virus containing 100 MID50 and 10 MID50. At the same time, the drug was administered by CHB by means of irrigation, and the Tamiflu control group was established at the same time. The test grouping method is shown in Table 2, and the drug was administered continuously by intragastric administration once a day. At the same time, the same dose of placebo was administered to the challenge control group and the blank control group.
  • mice The life indexes of the mice were observed and compared with the blank control group and the challenge control group. On the 5th day and the 7th day after the challenge, 5 mice were killed and the virus content of the lungs was titrated to determine the inhibitory effect of CHB on influenza virus replication in mice.
  • X -11 blank control group water PBS lOOul / ⁇ 10
  • X represents a virus subtype (as in Table 3, X takes 1 to represent the H1N1 subtype group, and in Table 4, X takes 3 to represent the H3N2 subtype group, and in Table 5, X takes 5 to represent the H5N1 subtype group. ).
  • PBS was a placebo, 0.1 M phosphate buffer.
  • the MID50 of A/swine/Guangdong/716/03 (HlNl subtype), A/swine/Guangdong/08/03 (H3N2 subtype) and A/swine/Fujian/l/03 (H5Nl subtype) strains are : 10 45 , 10 233 , 10 167 .
  • the avian influenza H5N1 experimental group had a maximum conversion rate of 80% for four days, Duffy had a maximum conversion rate of 40% for four days, and the glycoconjugate CHB was higher than Tamiflu. 100%.
  • the total conversion rate of the six-day administration of the glycoconjugate CHB in the influenza H1N1 experimental group was 35% on average, and the total conversion rate on the six-day administration of the Tamiflu control group was 55% on average.
  • the conjugate CHB was 57%.
  • the glycoconjugate CHB is a strong immunological two-way regulator.
  • the mechanism of its inhibition of the virus is immune regulation, and the immune response ability after virus infection determines the virus replication or The rate of clearance, this experiment shows that the glycoconjugate CHB can be used for prevention, treatment of influenza and avian influenza by immunomodulation.
  • Tamiflu is to block the replication of influenza and avian influenza virus by inhibiting neuraminidase, but it cannot remove the virus before administration.
  • the virus before use can only be turned off by the immune response. Therefore, the early treatment effect of Tamiflu is significantly lower than that of the glycoconjugate CHB and is not suitable for prevention.
  • glycoconjugate CHB is a natural glycoconjugate, with no toxic side effects.
  • the virus is highly variable.
  • the main enzyme for virus replication after mutation is not the enzyme designed by Tamiflu, and Tamiflu will lose its efficacy.
  • the bird flu virus has developed resistance to Tamiflu.
  • the immunological mechanism of the glycoconjugate CHB is to act on any virus, and the effect of the virus mutation on the glycoconjugate CHB is small. From the analysis of the present situation, the total conversion rate of the six-day treatment of the glycoconjugate CHB to H1N1, H3N2, and H5N1 was 35%, 35%, and 50%, respectively, while Duffy had six days for H1N1, H3N2, and H5N1. The total conversion rate of treatment was 55%, 27.5%, and 45%, respectively.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Virology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pulmonology (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne l'utilisation d'un glycoconjugué CHB pour préparer un médicament destiné au traitement ou à la prophylaxie de la grippe ou de la grippe aviaire, ledit glycoconjugué CHB état un composé de polysaccharide qui est isolé et extrait de sérum de tortue et/ou d'écaille de tortue.
PCT/CN2006/000433 2006-03-07 2006-03-20 Utilisation d'un glycoconjugué chb pour préparer un médicament destiné à la prophylaxie ou au traitement de la grippe ou de la grippe aviaire WO2007101370A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN200610038665.7 2006-03-07
CNB2006100386657A CN100421673C (zh) 2006-03-07 2006-03-07 糖缀合物chb在制备防治流感或禽流感药物中的应用

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WO2007101370A1 true WO2007101370A1 (fr) 2007-09-13

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PCT/CN2006/000433 WO2007101370A1 (fr) 2006-03-07 2006-03-20 Utilisation d'un glycoconjugué chb pour préparer un médicament destiné à la prophylaxie ou au traitement de la grippe ou de la grippe aviaire

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WO (1) WO2007101370A1 (fr)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107312079A (zh) * 2017-07-17 2017-11-03 华东师范大学 一种甲鱼血糖肽的分离提取方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1566151A (zh) * 2003-06-09 2005-01-19 吴志大 用鳖或/和龟的血清提取的糖缀合物chb和制备工艺及其在制药中的应用

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1566151A (zh) * 2003-06-09 2005-01-19 吴志大 用鳖或/和龟的血清提取的糖缀合物chb和制备工艺及其在制药中的应用

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CN1850105A (zh) 2006-10-25
CN100421673C (zh) 2008-10-01

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