WO2008077276A1 - Solution injectable de venin d'araignée et mode d'élaboration correspondant - Google Patents

Solution injectable de venin d'araignée et mode d'élaboration correspondant Download PDF

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Publication number
WO2008077276A1
WO2008077276A1 PCT/CN2006/003584 CN2006003584W WO2008077276A1 WO 2008077276 A1 WO2008077276 A1 WO 2008077276A1 CN 2006003584 W CN2006003584 W CN 2006003584W WO 2008077276 A1 WO2008077276 A1 WO 2008077276A1
Authority
WO
WIPO (PCT)
Prior art keywords
active
spider
toxin
venom
injection
Prior art date
Application number
PCT/CN2006/003584
Other languages
English (en)
Chinese (zh)
Inventor
Xuxu Zhang
Original Assignee
Graduate School At Shenzhen, Tsinghua University
Well Treasure Technology Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Graduate School At Shenzhen, Tsinghua University, Well Treasure Technology Limited filed Critical Graduate School At Shenzhen, Tsinghua University
Priority to PCT/CN2006/003584 priority Critical patent/WO2008077276A1/fr
Publication of WO2008077276A1 publication Critical patent/WO2008077276A1/fr

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Classifications

    • 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
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1767Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56Materials from animals other than mammals
    • A61K35/63Arthropods
    • A61K35/646Arachnids, e.g. spiders, scorpions, ticks or mites
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/04Centrally acting analgesics, e.g. opioids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents

Definitions

  • the invention relates to a medical preparation, in particular to a spider poison injection and a preparation method thereof.
  • Chronic pain includes: neck and shoulder pain; various chronic refractory neuralgia, such as trigeminal neuralgia, sciatica; cancer pain, 70% of cancer patients with pain in the middle and late stages; another like diabetes, frozen shoulder It can also cause chronic pain.
  • Acute pain after surgery can also turn into intractable chronic pain if not properly controlled. According to statistics, 30% to 35% of people suffer from chronic pain for a long time, and 5.5 million people suffer from chronic cancer pain every day in the world.
  • Spider venom can inhibit calcium channels and is a neurotoxin. Its main components are peptides and proteins, including polypeptide neurotoxins, cytotoxins, enzymes, kinin analogues, agglutination peptides and antimicrobial peptides, in addition to polyamines and low ATP, nucleotides, amino acids, monoamines. Molecular weight substance And inorganic salts, etc.
  • Spider toxin is a neurotoxin that has a significant excitatory effect on the heart, blood vessels and skeletal muscle. A small amount of spider toxin is not only harmless to the human body, but also exhibits a benign regulation function, which can restore the local tissue and organ function from hyperthyroidism or weakened state to normal state. Spider toxin also has good anti-inflammatory, analgesic, anti-tumor, antispasmodic, hurricane and other effects, has a two-way regulation of human immune function.
  • Another object of the present invention is to provide a method for preparing the above-mentioned spider poison injection.
  • the content of the active spider toxin is 0. 5mg ⁇ 5mg/100ml.
  • the active spider toxin used in the present invention is active Huwentoxin or active scorpion toxin, and can also be active Chilean spider toxin, active black widow spider toxin, active American funnel web spider toxin, active funnel web spider toxin , active black-bellied spider toxin or active tarantula toxin.
  • the injectable solution used in the present invention may be distilled water, physiological saline or a glucose solution for injection.
  • the preparation method of the spider poison injection of the invention comprises the following steps:
  • the living spider induces the poisoning method to extract the active spider venom.
  • the specific steps are as follows: a) Take the adult spider from the feeding tube with a long tweezers, clip or chopsticks and put it in a common plastic bucket or ordinary plastic laundry tub; b Use the above-mentioned tweezers, clips or chopsticks to tease the cat's head in front of the spider's head. The spider will lift the predecessor and open the poisonous cheek to attack the teasing. At this time, avoid the spider directly biting the teasing object.
  • the body can be gently pressed with the teasing object, and the hand with the soft leather glove can be directly grasped from the middle of the spider body; d) Point the spider poison to the mouth of the grinding bottle or the hard plastic bottle. When the spider bites the bottle, the venom will be released immediately. The venom is observed as a transparent liquid.
  • Another person uses a micro-syringe to take the venom in the bottle at the mouth. Inject the venom into the test tube or cell tube, and place the cell tube or test tube into the vacuum cup with ice cubes in time to prevent the extraction process from taking a long time to increase the temperature of the venom.
  • the spider venom injection of the invention is mainly used for treating collective immunity 'allergy caused by various causes and various cancers, and can also be used for treating nerve pain such as rheumatism, rheumatoid arthritis and trigeminal neuralgia and sciatica. Inhibition tests on central and peripheral nerves have demonstrated good analgesic effects on neuropathic pain.
  • the spider poison injection of the invention retains the activity of spider venom, and opens up a new way for clinical treatment of various diseases. detailed description
  • the active venom of the tiger-winged tarantula is extracted from the live bird-trapping spider, iSelenocosmia Huwena.
  • the specific steps are as follows: 1) The adult tiger-winged tarantula uses a longer scorpion from the feeding tube. Take it out and put it in a regular plastic bucket or a normal plastic washtub. 2) Use the above-mentioned scorpion as a teasing object to tease the front of the spider's head. The spider will lift the front body and open the poisonous cheek to attack the teasing.
  • the active venom of the venomous spider venom was prepared under vacuum conditions at a pressure of 0.1 atm. by conventional lyophilization to form a white active tiger venom toxin crystal at a temperature of 45 ° C.
  • the above method can also be used to prepare active Chilean spider toxin, active black widow spider toxin, active American funnel web spider toxin, active funnel net spider toxin, active black belly spider toxin or active tarantula injection, the injection solution used. It is distilled water, physiological saline or glucose solution. The activity of the spider venom injection is illustrated by the following test.
  • the formaldehyde inflammation method was used, and 0.1 ml of 2% formaldehyde was injected between the third and fourth joints of the right hind leg of the rat, resulting in arthritis. After 24 hours, the joint swelling reached a maximum. Then, the blank group and the drug-administered group were compared, and the circumference of the joint and the time of disappearance of arthritis were recorded, and the average value of the joint circumference was calculated.
  • the administration group was administered subcutaneously, and the dose was once a day, each time lml of T. sinensis injection, the concentration of the injection was 0.01 mg/ml, and the injection solution was sterile distilled water.
  • the blank group was injected subcutaneously with sterile distilled water once a day for 1 ml each time. In this experiment, three-week-old rats were used, weighing 180-220 g, with 8 rats in each group.
  • Test method Using mouse writhing test
  • 0.2 ml of 0.6% acetic acid was used to cause pain in mice by direct gavage, and it was administered after 5 minutes of pain.
  • the blank group was subcutaneously injected with distilled water once a day, each time 1 ml was injected; the drug-administered group was injected subcutaneously with the tiger-shaped bird venom injection, the concentration of the injection was 0.01 mg/ml, and the injection solution was sterile distilled water once a day. , lml each time. Then observe the number of writhings in 60 minutes and calculate the average. This experiment used adult male mice weighing 18 to 22 g, 8 in each group.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Rheumatology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Dermatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Insects & Arthropods (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne, d'une part une solution injectable de venin d'araignée présentant une activité analgésique, et d'autre part le mode d'élaboration correspondant. La présente solution injectable convient particulièrement en cas de rhumatisme, d'affections rhumatoïdes et de névralgie.
PCT/CN2006/003584 2006-12-25 2006-12-25 Solution injectable de venin d'araignée et mode d'élaboration correspondant WO2008077276A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/CN2006/003584 WO2008077276A1 (fr) 2006-12-25 2006-12-25 Solution injectable de venin d'araignée et mode d'élaboration correspondant

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2006/003584 WO2008077276A1 (fr) 2006-12-25 2006-12-25 Solution injectable de venin d'araignée et mode d'élaboration correspondant

Publications (1)

Publication Number Publication Date
WO2008077276A1 true WO2008077276A1 (fr) 2008-07-03

Family

ID=39562068

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2006/003584 WO2008077276A1 (fr) 2006-12-25 2006-12-25 Solution injectable de venin d'araignée et mode d'élaboration correspondant

Country Status (1)

Country Link
WO (1) WO2008077276A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1133461C (zh) * 2000-04-11 2004-01-07 厦门北大之路生物工程有限公司 虎纹捕鸟蜘蛛毒素提取物在制备镇痛药物中的应用
CN1839888A (zh) * 2005-12-22 2006-10-04 清华大学深圳研究生院 一种蜘蛛毒注射液及其制备方法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1133461C (zh) * 2000-04-11 2004-01-07 厦门北大之路生物工程有限公司 虎纹捕鸟蜘蛛毒素提取物在制备镇痛药物中的应用
CN1839888A (zh) * 2005-12-22 2006-10-04 清华大学深圳研究生院 一种蜘蛛毒注射液及其制备方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHEN JIAXUN ET AL.: "Analgesic effect of huwentoxin-I, a new N-type voltage-sensitive calcium channel blocker, on acute visceral pain in rats", JOURNAL OF FIRST MILLITARY MEDICAL UNIVERSITY, vol. 25, no. 10, pages 10 - 14 *

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