WO2004080471A1 - Nouvelle utilisation du venin de scorpion comme substance de traitement du paludisme et de prophylaxie - Google Patents
Nouvelle utilisation du venin de scorpion comme substance de traitement du paludisme et de prophylaxie Download PDFInfo
- Publication number
- WO2004080471A1 WO2004080471A1 PCT/EG2004/000009 EG2004000009W WO2004080471A1 WO 2004080471 A1 WO2004080471 A1 WO 2004080471A1 EG 2004000009 W EG2004000009 W EG 2004000009W WO 2004080471 A1 WO2004080471 A1 WO 2004080471A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- venom
- malaria
- scorpion venom
- scorpion
- blood
- Prior art date
Links
- 201000004792 malaria Diseases 0.000 title claims abstract description 36
- 239000002795 scorpion venom Substances 0.000 title claims abstract description 22
- 238000011282 treatment Methods 0.000 title claims description 12
- 238000011321 prophylaxis Methods 0.000 title claims 4
- 239000002435 venom Substances 0.000 claims abstract description 27
- 231100000611 venom Toxicity 0.000 claims abstract description 27
- 210000001048 venom Anatomy 0.000 claims abstract description 27
- 210000001563 schizont Anatomy 0.000 claims abstract description 17
- 244000045947 parasite Species 0.000 claims abstract description 14
- 238000011161 development Methods 0.000 claims abstract description 6
- 210000000987 immune system Anatomy 0.000 claims abstract description 3
- 238000002360 preparation method Methods 0.000 claims description 9
- 238000002347 injection Methods 0.000 claims description 7
- 239000007924 injection Substances 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 5
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 claims description 4
- 230000009471 action Effects 0.000 claims description 2
- 229960001340 histamine Drugs 0.000 claims description 2
- 230000035935 pregnancy Effects 0.000 claims description 2
- 241000059425 Periclimenes imperator Species 0.000 claims 4
- 241000894007 species Species 0.000 claims 2
- 239000002552 dosage form Substances 0.000 claims 1
- 230000007246 mechanism Effects 0.000 claims 1
- 231100000957 no side effect Toxicity 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 14
- 229940079593 drug Drugs 0.000 abstract description 14
- 239000003430 antimalarial agent Substances 0.000 abstract description 5
- 230000028993 immune response Effects 0.000 abstract 1
- 210000004369 blood Anatomy 0.000 description 28
- 239000008280 blood Substances 0.000 description 28
- 238000010790 dilution Methods 0.000 description 13
- 239000012895 dilution Substances 0.000 description 13
- 230000000694 effects Effects 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 5
- 241000239226 Scorpiones Species 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 4
- WOGWYSWDBYCVDY-UHFFFAOYSA-N 2-chlorocyclohexa-2,5-diene-1,4-dione Chemical compound ClC1=CC(=O)C=CC1=O WOGWYSWDBYCVDY-UHFFFAOYSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000012894 fetal calf serum Substances 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000035800 maturation Effects 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 206010035500 Plasmodium falciparum infection Diseases 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 239000003053 toxin Substances 0.000 description 3
- 231100000765 toxin Toxicity 0.000 description 3
- 108700012359 toxins Proteins 0.000 description 3
- 208000035473 Communicable disease Diseases 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 208000002476 Falciparum Malaria Diseases 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 208000030852 Parasitic disease Diseases 0.000 description 2
- 241000224016 Plasmodium Species 0.000 description 2
- 241000223960 Plasmodium falciparum Species 0.000 description 2
- 201000011336 Plasmodium falciparum malaria Diseases 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000000078 anti-malarial effect Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 230000003071 parasitic effect Effects 0.000 description 2
- 238000011886 postmortem examination Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- 210000001835 viscera Anatomy 0.000 description 2
- NALREUIWICQLPS-UHFFFAOYSA-N 7-imino-n,n-dimethylphenothiazin-3-amine;hydrochloride Chemical compound [Cl-].C1=C(N)C=C2SC3=CC(=[N+](C)C)C=CC3=NC2=C1 NALREUIWICQLPS-UHFFFAOYSA-N 0.000 description 1
- 108010023798 Charybdotoxin Proteins 0.000 description 1
- 241000255925 Diptera Species 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 208000032023 Signs and Symptoms Diseases 0.000 description 1
- 208000002474 Tinea Diseases 0.000 description 1
- 241000893966 Trichophyton verrucosum Species 0.000 description 1
- 150000007854 aminals Chemical class 0.000 description 1
- 230000004099 anaerobic respiration Effects 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000003659 bee venom Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 210000004903 cardiac system Anatomy 0.000 description 1
- 239000010627 cedar oil Substances 0.000 description 1
- CNVQLPPZGABUCM-LIGYZCPXSA-N ctx toxin Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@H]3CSSC[C@@H](C(N[C@@H](CC=4C5=CC=CC=C5NC=4)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CCCNC(N)=N)NC3=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CO)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3NC=NC=3)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N2)C(C)C)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H]([C@@H](C)O)NC1=O)=O)CCSC)C(C)C)[C@@H](C)O)NC(=O)[C@H]1NC(=O)CC1)C1=CC=CC=C1 CNVQLPPZGABUCM-LIGYZCPXSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000003547 immunosorbent Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 238000012332 laboratory investigation Methods 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 210000000287 oocyte Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1767—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- the 1 st aim of malaria treatment was to destroy the malaria parasite in blood at the 17 century Indians used sincona tree as a source of quinone drug for malaria treatment.
- the drug mode of action inside the body is unknown .
- Figl represents the relation between the venom concentration and the number of schizonts showing that the dose of 15 ⁇ g/ml or more of the venom has an inhibition effect on the development schizont from the asexual form.
- Fig2 represents the relation between the venom concentration and the number of ring form & plasmodium species showing that there is a decrease in ring form with the increase of venom concentration.
- this experiment can estimate the degree of malaria protozoa sensitivity against scorpion venom where it estimates the Inhibition of the schizont phase after Incubation with venom dilutions for 16-48 hours at 37°c in anaerobic condition and that determined
- Day 1 the 1 st dose volume 400 ⁇ l s/c.
- Day 7 the 2 nd dose volume 450 ⁇ l s/c.
- Day 14 the 3 rd dose volume 500 ⁇ l s/c.
- Kitu (1997), reported that Malaria due to plasmodium falciparum is probably the most important infectious disease in the tropical world .In Africa south of the Sahara alone ,over one million children die annually as of malaria . It is a difficult parasitic disease both to diagnose and control. It is not provide sterile immunity even after long exposure periods.
- Cytokines are responsible for many of the symptoms and signs of the Infection. Cytokine levels measured by enzyme linked immunosorbent.
- ELISA Assay
- IRMA indirect fluorescent antibody test
- pandinotoxins ,pitx-k alpha and pitx-k, beta are members of the charybdotoxin family of scorpion toxin that can be used to characterize k+ channels.
- Pitx-k alpha differs from pitx-k beta.
- _I_ ood samples were collected from infected patient using sterile needle & heparenie ⁇ zed vacutainers .
- test measures Inhibition schizonte growth after incubation of parasitised blood at various venom dilutions for 36-4 ⁇ hours at 37c
- venous blood drawn into sterile heparenized tube were added to 900 ml of RPMI medium and 1.5 ml of fetal calf serum.Gentle agetation was done to mix the blood and medium ,using sterile eppendorf pipette tips .
- 50 ml of blood medium mixture were added to each well of predosed WHO tissue culture microtiter plate (falcon 3071,Decton Dickinson ,New jersey ,USA ). The well are predosed with diffirent dilutions of scorpion venom (250,125,60,30,15,8,4,2,l,and 0.5 ⁇ g) of venom.
- tissue culture plate was gently shaken t&them Incubated in candle jar at 37 C for 36-48 hrs. After incubation the contents of the wells were harvested by removing the supernatant and collecting the red blood cells deposited on the bottom for subsequent preparation
- MIC Minimum inhibitory concentration
- the log probit regression line is a good summary of the results of a group of tests, describing the average behaviour of the corresponding parasite population in response to increasing drug concentration (Molineaux et al., 1988).
- Scorpion fraction is an antimalaria agent purified from Scorpion venom.
- the present work therefore is an introductory trials to understand the effect of scorpion venom on malaria life cycle.
- the drugs used for the treatment of severe malaria all act predominantly in the middle third of the life cycle by inhibiting schizont growth and this was considered successful to cut the malaria life cycle and thus considered successful trials for our drug (molineux et al.,1988) since the inhibition of the life cycle stages maturation was at doses >15 ug/ml of the venom. So we can use this dilution and even more at in vivo trials (secondary trials) to evaluate our drug as pre-clinical trials.
- Second Inject multi doses every week in rat, beginning with dose more than LD50 (400 ug/ml) after 3 successive doses take blood sample from control and injected rat to evaluate the effect of the venom on hematology anf serology of the animal. And after that kill the animal to study the pathological effect of this venom on various organs.
- LD50 400 ug/ml
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Tropical Medicine & Parasitology (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
L'invention concerne un médicament à base de venin de scorpion qui agit comme médicament antipaludique. Le médicament de l'invention contient des fractions qui agissent comme des inhibiteurs et suppresseurs du cycle de vie du paludisme à des doses particulières. Il a été démontré que le venin de l'invention a la capacité d'arrêter le développement du cycle vital asexué du stade de noyau à celui de schizonte. A l'effet de protection, l'objectif est d'utiliser des doses particulières du venin de scorpion pour stimuler le système immunitaire et induire une réaction immunitaire spécifique contre le parasite du paludisme.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EG2003030247 | 2003-03-12 | ||
| EG2003030247A EG23600A (en) | 2003-03-12 | 2003-03-12 | Treatment and prophylatic drug for malaria |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2004080471A1 true WO2004080471A1 (fr) | 2004-09-23 |
Family
ID=43875565
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EG2004/000009 WO2004080471A1 (fr) | 2003-03-12 | 2004-03-06 | Nouvelle utilisation du venin de scorpion comme substance de traitement du paludisme et de prophylaxie |
Country Status (2)
| Country | Link |
|---|---|
| EG (1) | EG23600A (fr) |
| WO (1) | WO2004080471A1 (fr) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011022357A3 (fr) * | 2009-08-17 | 2011-06-16 | East Carolina University | Enzymes de clivage de snare à action rapide |
| CN107574216A (zh) * | 2017-09-29 | 2018-01-12 | 南京仙草堂生物科技有限公司 | 一种蝎毒素的提取和纯化工艺 |
-
2003
- 2003-03-12 EG EG2003030247A patent/EG23600A/xx active
-
2004
- 2004-03-06 WO PCT/EG2004/000009 patent/WO2004080471A1/fr unknown
Non-Patent Citations (2)
| Title |
|---|
| CONDE R. ET AL.: "Scorpine, an antimalaria and anti bacterial agent purified from scorpion venom.", FEBS LETTERS 471, vol. 2000, pages 165 - 168 * |
| POSSANI L.D.: "From noxiustoxin to scorpine and possible transgenic mosquitos resistant to malaria", ARCHIVES OF MEDICAL RESEARCH, vol. 33, no. 4, 2002, pages 398 - 407 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011022357A3 (fr) * | 2009-08-17 | 2011-06-16 | East Carolina University | Enzymes de clivage de snare à action rapide |
| US9149666B2 (en) | 2009-08-17 | 2015-10-06 | East Carolina University | Fast acting SNARE-cleaving enzymes |
| CN107574216A (zh) * | 2017-09-29 | 2018-01-12 | 南京仙草堂生物科技有限公司 | 一种蝎毒素的提取和纯化工艺 |
Also Published As
| Publication number | Publication date |
|---|---|
| EG23600A (en) | 2006-10-02 |
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