WO2021060862A1 - Composition pharmaceutique pour la prévention ou le traitement de la malaria, contenant du fucoïdane en tant que principe actif - Google Patents
Composition pharmaceutique pour la prévention ou le traitement de la malaria, contenant du fucoïdane en tant que principe actif Download PDFInfo
- Publication number
- WO2021060862A1 WO2021060862A1 PCT/KR2020/012940 KR2020012940W WO2021060862A1 WO 2021060862 A1 WO2021060862 A1 WO 2021060862A1 KR 2020012940 W KR2020012940 W KR 2020012940W WO 2021060862 A1 WO2021060862 A1 WO 2021060862A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- chloroquine
- fucoidan
- malaria
- preventing
- active ingredient
- Prior art date
Links
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Images
Classifications
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- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/737—Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4706—4-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/324—Foods, ingredients or supplements having a functional effect on health having an effect on the immune system
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/30—Other Organic compounds
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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- A23V2250/00—Food ingredients
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
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- 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 present invention relates to a composition comprising fucoidan as an active ingredient, and more particularly, a pharmaceutical composition for preventing or treating malaria comprising fucoidan as an active ingredient, and a health functional food for preventing or improving malaria comprising fucoidan as an active ingredient It relates to the composition.
- Malaria is an acute and often chronic infectious disease caused by the presence of protozoan parasites in red blood cells. Malaria caused by single-celled parasites in the genus Plasmodium is transmitted from person to person by biting by female mosquitoes. The transmission of malaria is initiated when a female mosquito bites a person already infected with the malaria parasite. When an infected mosquito bites another person, the sporozoite in mosquito saliva passes into the blood and then into the liver. In the liver, sporozoites rapidly divide, then enter the bloodstream and invade red blood cells. Inside these erythrocytes, merocite proliferates rapidly until it ruptures the red blood cells, thereby releasing a new generation of merozite into the bloodstream, which subsequently infects other red blood cells.
- Red blood cells Malaria-related symptoms are generally associated with rupture of red blood cells. The destruction of red blood cells leaks waste materials, toxins, and other debris into the blood, which leads to extreme fever, anemia, severe headaches, convulsions, and mental confusion. In addition to symptoms such as back, severe cases lead to death.
- quinine an antimalarial compound extracted from the bark of the South American cinchona tree
- quinine is short-acting and does not prevent recurrence of the disease, and has a disadvantage in that it causes side effects such as dizziness and hearing loss.
- the present invention has been devised to solve the above-described problems, and in the present invention, it is intended to provide a pharmaceutical composition for preventing or treating malaria comprising fucoidan as an active ingredient.
- the present invention provides a pharmaceutical composition for preventing or treating malaria comprising fucoidan as an active ingredient.
- the present invention also provides a health functional food composition for preventing or improving malaria comprising fucoidan as an active ingredient.
- composition comprising fucoidan according to the present invention as an active ingredient is a natural substance derived from brown algae, and can overcome resistance and low sensitivity to chloroquine by preventing invasion into red blood cells through adsorption of malaria protozoa without side effects. When mixed with phosphorus chloroquine in a predetermined ratio, the effect is further increased, and thus it can be usefully used as a new malaria treatment.
- Figure 1 is a chloroquine sensitive strain 3D7 strain ( Figure 1 (a)) and chloroquine resistant strain Dd2 strain ( Figure 1 (b)) inoculated into normal red blood cells, distilled water, chloroquine 100 nM (about 51.5 ng/ml) or 200 After nM (about 103 ng/ml) treatment, a graph showing the result of measuring the malaria infection rate for 48 hours in units of 24 hours.
- Figure 2 is a chloroquine sensitive strain 3D7 strain ( Figure 2 (a)) and chloroquine resistant strain Dd2 strain ( Figure 2 (b)) inoculated into normal red blood cells, distilled water, chloroquine 200 nM (about 51.5 ng/ml), fucoidan
- Figure 2 (a) a chloroquine sensitive strain 3D7 strain
- Figure 2 (b) chloroquine resistant strain Dd2 strain
- Figure 2 (b) inoculated into normal red blood cells, distilled water
- chloroquine 200 nM about 51.5 ng/ml
- fucoidan A graph showing the result of measuring the malaria infection rate for 48 hours in units of 24 hours after a combination treatment of 20 ⁇ g/ml or 200 nM of chloroquine and 20 ⁇ g/ml fucoidan (mixed in a volume ratio of 1:1).
- Figure 3 is a chloroquine sensitive strain 3D7 strain and chloroquine resistant strain Dd2 strain distilled water, chloroquine 200 nM (about 51.5 ng / ml) or chloroquine 200 nM and fucoidan 20 ⁇ g / ml complex treatment (mixed in a volume ratio of 1: 1) after, This is a graph confirming the statistical significance between each group after 48 hours.
- Figure 6 is a graph showing the results of measuring red blood cell survival rate according to treatment of chloroquine (100 nM), fucoidan (20 ⁇ g/ml) and histidine concentrations (10 nM, 100 nM, 1000 nM) when culturing the Dd2 strain, a chloroquine resistant strain.
- nM 7 is a chloroquine-resistant strain Dd2 strain incubation of chloroquine (100 nM) and fucoidan (20 ⁇ g/ml) and histidine concentrations (10 nM, 100 nM, 1000 nM) in addition to the concentrations of histidine (10 nM).
- 100 nM, 1000 nM is a graph showing the result of measuring the change in the number of protozoa according to the treatment (measured after 48 hours).
- the present invention relates to a pharmaceutical composition for the prevention or treatment of malaria comprising fucoidan as an active ingredient in one tube.
- the present invention relates to a health functional food composition for preventing or improving malaria comprising fucoidan as an active ingredient from another perspective.
- composition is considered to include not only products containing certain ingredients, but also any products made directly or indirectly by the combination of certain ingredients.
- treatment refers to (a) inhibition of the development of a disease, disease or condition; (b) alleviation of the disease, disease or condition; Or (c) to eliminate a disease, disease or condition.
- the composition of the present invention inhibits the effect of malaria infection by improving the survival rate of malaria-infected cells, or inhibits the generation, proliferation and replication of malaria protozoa, thereby inhibiting the development of a disease or symptoms thereof, which causes malaria infection, or It serves to eliminate or alleviate it.
- the composition of the present invention may itself be a therapeutic composition for a malaria infection disease, or may be administered together with another therapeutic agent for malaria and applied as a therapeutic adjuvant for suppressing malaria infection.
- treatment aid or "treatment aid”.
- prevention refers to suppressing the occurrence of a disease or disease in a subject that has not been diagnosed with a disease or disease, but is likely to have such a disease or disease.
- administering refers to directly administering a therapeutically effective amount of a composition of the present invention to a subject so that the same amount or an amount corresponding thereto is formed in the body of the subject.
- the pharmaceutical composition may be characterized in that it contains a pharmaceutically acceptable carrier, wherein the carrier is an ion exchange resin, alumina, aluminum stearate, lecithin, serum protein, buffer material, water, salt, Electrolyte, colloidal silica, magnesium trisilicate, polyvinylpyrrolidone, cellulose-based substrate, polyethylene glycol, sodium carboxymethylcellulose, polyarylate, wax, polyethylene glycol, and wool paper.
- the carrier is an ion exchange resin, alumina, aluminum stearate, lecithin, serum protein, buffer material, water, salt, Electrolyte, colloidal silica, magnesium trisilicate, polyvinylpyrrolidone, cellulose-based substrate, polyethylene glycol, sodium carboxymethylcellulose, polyarylate, wax, polyethylene glycol, and wool paper.
- the carrier is an ion exchange resin, alumina, aluminum stearate, lecithin, serum protein, buffer material, water, salt, Electrolyte, colloidal
- the pharmaceutical composition is formulated for intravenous, intraperitoneal, intramuscular, intraarterial, oral, intracardiac, intramedullary, intrathecal, transdermal, intestinal, subcutaneous, sublingual or topical administration. It may be characterized in that it further contains any one or more adjuvants selected from the group consisting of buffers, antimicrobial preservatives, surfactants, antioxidants, tonicity modifiers, preservatives, thickeners and viscosity modifiers, solutions, suspensions, emulsions , It may be characterized in that it has a formulation selected from the group consisting of gels and powders.
- a suitable dosage of the pharmaceutical composition of the present invention varies depending on factors such as the severity of symptoms, weight, age, sex, mode of administration and time of administration of the patient, and generally skilled physicians are effective in the desired treatment or prevention.
- the dosage can be easily determined.
- the health functional food refers to a food manufactured and processed using raw materials or ingredients having useful functions for the human body according to the Health Functional Food Act No. 6722, and contains nutrients for the structure and function of the human body. It refers to food consumed for the purpose of controlling or obtaining beneficial effects for health purposes such as physiological effects.
- the health functional food composition of the present invention may be formulated in a formulation of a general health functional food known in the art, and granules, tablets, pills, suspensions, emulsions, syrups, gums, teas, jellies, various beverages, and drinks. , Alcoholic beverages, etc., and there is no particular limitation on the kind of the health functional food.
- the health functional food composition of the present invention is in any herbal form suitable for administration to an animal body including the human body, more specifically any form conventional for oral administration, for example, food or feed, food or feed additives and adjuvants, It may be in a solid form such as fortified food or feed, tablets, pills, granules, capsules and foam formulations, or in liquid form such as solutions, suspensions, emulsions, beverages, pastes, etc., and nutrients, vitamins, electrolytes, sweeteners, coloring agents, organic acids, It may contain a preservative or the like, and these ingredients may be used independently or in combination.
- the composition may be characterized in that it further comprises chloroquine.
- the volume ratio of chloroquine and fucoidan contained in the composition is preferably 10:1 to 1:10, and 5:1 to 1:2 and 1:10, as can be seen from the results of the following examples. More preferable.
- the composition may be characterized in that it further comprises histidine in addition to chloroquine.
- the concentration ratio of chloroquine and histidine contained in the composition is preferably 1:0.1-10, as can be seen from the results of the following examples.
- the present invention provides a method for preventing or treating malaria or malaria infectious disease comprising administering a therapeutically effective amount of the pharmaceutical composition to a mammal.
- mammal refers to a mammal that is the object of treatment, observation or experiment, and preferably refers to a human.
- the term "therapeutically effective amount” refers to an amount of an active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, animal or human thought by a researcher, veterinarian, doctor or other clinician, which Includes an amount that induces relief of symptoms of the disease or disorder being treated. It is apparent to those skilled in the art that the therapeutically effective dosage and frequency of administration of the active ingredient of the present invention will vary depending on the desired effect. Therefore, the optimal dosage to be administered can be easily determined by those skilled in the art, and the type of disease, the severity of the disease, the content of active ingredients and other ingredients contained in the composition, the type of formulation, and the age, weight, and general health condition of the patient. , Sex and diet, administration time, administration route and secretion rate of the composition, treatment period, it may be adjusted according to various factors including drugs used simultaneously.
- the malaria protozoa P. falciparum 3D7 and Dd2 strains used in this experimental example were collected from patients infected with each strain and subcultured in a laboratory-adapted manner, and the culture method was Trager and Jensen's method (1976). It was transformed and used. That is, it was prepared by adding 0.25% AlbuMAX, 0.05% hypoxanthine, 25 mM HEPES buffer, 0.225% sodium bicarbonate, and 10 ⁇ g/ml gentamycin to RPMI 1640. The prepared culture solution was divided into a T-25 flask, and then normal red blood cells and 3D7 and Dd2 strains were inoculated.
- diphosphorylated chloroquine (Sigma) 5 mg and fucoidan (Sigma) 2 mg were dissolved in distilled water or phosphate buffered saline (PBS) and diluted appropriately to prepare a stock solution for dissolving chloroquine and fucoidan.
- PBS phosphate buffered saline
- alanine, arginine, histidine, lysine and valine purchased from Sigma were prepared at a concentration of 100 ⁇ M.
- the prepared flask was injected with a mixture gas composed of each treatment drug and 5% O 2 , 5% CO 2 and 90% N 2 , sealed, and cultured in an incubator at 37°C. During the experiment, parasite blood was stained by Wright stain method and confirmed under a microscope.
- Each dissolution stock solution prepared above was appropriately diluted, and a final concentration of 100 nM or 200 nM of chloroquine was treated in a flask inoculated with 3D7 and Dd2, and the malaria infection rate was measured for 48 hours every 24 hours, and the results are as follows. It is shown in Figure 1.
- Figure 1 is a chloroquine sensitive strain 3D7 strain ( Figure 1 (a)) and chloroquine resistant strain Dd2 strain ( Figure 1 (b)) inoculated into normal red blood cells, distilled water, chloroquine 100 nM (about 51.5 ng/ml) or 200 After nM (about 103 ng/ml) treatment, a graph showing the result of measuring the malaria infection rate for 48 hours in units of 24 hours.
- the experimental results showed that the 3D7 strain, a chloroquine-sensitive strain, significantly decreased parasitemia after 48 hours depending on the treatment concentration of chloroquine, whereas the Dd2 strain, a chloroquine-resistant strain, was treated with chloroquine after 48 hours. No concentration-dependent reduction of parasites was observed.
- the experiment was conducted by dividing the 3D7 strain, which is a tropical malaria chloroquine sensitive strain, and the Dd2 strain, which is a chloroquine resistant strain, into a control group, a chloroquine 200 nM treatment group, a fucoidan 20 ⁇ g/mL treatment group, and a chloroquine and fucoidan complex treatment group.
- the complex treatment of chloroquine and fucoidan the same volume ratio (1:1) of the stock solution of chloroquine and fucoidan was used.
- Figure 2 is a chloroquine sensitive strain 3D7 strain ( Figure 2 (a)) and chloroquine resistant strain Dd2 strain ( Figure 2 (b)) inoculated into normal red blood cells, distilled water, chloroquine 200 nM (about 51.5 ng/ml), fucoidan
- Figure 2 (a) a chloroquine sensitive strain 3D7 strain
- Figure 2 (b) chloroquine resistant strain Dd2 strain
- Figure 2 (b) inoculated into normal red blood cells, distilled water
- chloroquine 200 nM about 51.5 ng/ml
- fucoidan A graph showing the result of measuring the malaria infection rate for 48 hours in units of 24 hours after a combination treatment of 20 ⁇ g/ml or 200 nM of chloroquine and 20 ⁇ g/ml fucoidan (mixed in a volume ratio of 1:1).
- Figure 3 is a chloroquine sensitive strain 3D7 strain and chloroquine resistant strain Dd2 strain distilled water, chloroquine 200 nM (about 51.5 ng / ml) or chloroquine 200 nM and fucoidan 20 ⁇ g / ml complex treatment (mixed in a volume ratio of 1: 1) after, This is a graph confirming the statistical significance between each group after 48 hours.
- FIG. 3A is a result of confirming the statistical significance between the treated chloroquine-sensitive strain 3D7 strain and the chloroquine-resistant strain Dd2 strain, and it was confirmed that there was a significant difference in parasitic congestion results in the chloroquine-treated group.
- Figure 3 (b) is a result of confirming the statistical significance between distilled water, chloroquine or chloroquine and fucoidan complex treatment group in the 3D7 strain, which is a chloroquine sensitive strain, as a result of parasitic congestion between chloroquine alone treatment group and chloroquine and fucoidan complex treatment group. There was no difference, and FIG.
- the change in the number of protozoa of the Dd2 strain according to the mixing ratio (volume ratio) of fucoidan and chloroquine was measured, and the results are shown in FIG. 4 below.
- the mixing ratio experiment was performed by setting the volume ratio of chloroquine and fucoidan stock solution to 10:1 (187.6ng/ml: 3.64 ⁇ g/ml), 5:1 (171.9ng/ml: 6.7 ⁇ g) in the same total amount (200 ⁇ l) of 1:1 volume ratio.
- Chloroquine According to the complex treatment of amino acids Chloroquine tolerance Tropical heat Malaria infection rate measurement
- the protozoal infection rate was significantly reduced from 8.9% (0 hours) to 2.9% (48 hours) when combined with histidine. Considering that the 8.8% protozoan infection rate at 0 hours decreased to 5.9% after 48 hours in the group treated with chloroquine 200 nM alone, the protozoal infection rate decreased by more than two times through the combination treatment of chloroquine and histidine. Was confirmed.
- the combination treatment by concentration of chloroquine (100 nM), fucoidan (20 ⁇ g/ml) and histidine was compared to the negative control group (distilled water treatment group) compared to the survival rate of red blood cells (number of red blood cells / number of red blood cells after 48 hours / number of red blood cells) ) was found to increase significantly.
- the negative control group distilled water treatment group
- red blood cells number of red blood cells / number of red blood cells after 48 hours / number of red blood cells
- the chloroquine-fucoidan-histidine complex treatment group was 77%, 75%, and 81 in the combined treatment groups with histidine concentrations of 10 nM, 100 nM and 1000 nM, respectively.
- red blood cell survival rate was 77% in the chloroquine 100 nM, fucoidan 20 ⁇ g/ml and histidine 10 nM combination treatment group compared to the chloroquine 100 nM treatment group, which showed a 70% red blood cell survival rate, confirming that the red blood cell survival rate was significantly increased. I did.
- chloroquine (200 nM) and fucoidan (20 ⁇ g / ml) complex treatment group showed a protozoal infection rate of 1.32%
- fucoidan (20 ⁇ g / ml) and histidine Complex treatments by concentration showed 2.58%, 1.79%, and 1.71% protozoal infection rates, respectively, after 48 hours of cultivation.
- the combination treatment of chloroquine (100 nM), fucoidan (20 ⁇ g/ml) and histidine (100 nM or 1000 nM) was equivalent to the combination treatment of chloroquine (200 nM) and fucoidan (20 ⁇ g/ml). It was confirmed that the protozoal infection rate was shown, and through this, it was confirmed that the excellent effect of reducing the number of protozoa can be exhibited even under a low concentration of chloroquine when histidine is additionally included.
- composition of the present invention can overcome resistance and low sensitivity to chloroquine, and when mixed with chloroquine, which is a conventional therapeutic agent, in a predetermined ratio, the effect is further increased, and thus it can be usefully used as a new malaria treatment.
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Abstract
La présente invention concerne une composition contenant du fucoïdane en tant que principe actif et, plus spécifiquement, une composition pharmaceutique pour la prévention ou le traitement de la malaria, contenant du fucoïdane en tant que principe actif; et une composition de complément alimentaire pour prévenir ou soulager la malaria, contenant du fucoïdane en tant que principe actif. La composition contenant du fucoïdane en tant que principe actif, selon la présente invention, est une substance naturelle dérivée d'algues brunes, et empêche le Plasmodium de pénétrer, par adsorption, dans les érythrocytes sans effets secondaires, ce qui permet de surmonter la résistance à la chloroquine et une faible sensibilité, et si elle est mélangée dans un rapport prédéterminé avec la chloroquine, qui est un agent de traitement classique, son effet augmente encore et ainsi la présente invention peut être efficacement utilisée en tant que nouvel agent pour le traitement de la malaria.
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US20050090480A1 (en) * | 2003-10-22 | 2005-04-28 | Council Of Scientific & Industrial Research | Use of selected amino acid-zinc complexes as anti-malarials |
US20050171063A1 (en) * | 2003-10-20 | 2005-08-04 | Pawan Malhotra | Use of phosphono derivatives as anti-malarials |
US20140322240A1 (en) * | 2011-11-22 | 2014-10-30 | The University Court Of The University Of Edinburg | Malaria vaccine |
JP2017512498A (ja) * | 2014-03-28 | 2017-05-25 | フラウンホーファーゲゼルシャフト ツール フォルデルング デル アンゲヴァンテン フォルシユング エー.フアー. | 複数成分複数段階マラリアワクチン |
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- 2020-09-24 WO PCT/KR2020/012940 patent/WO2021060862A1/fr active Application Filing
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US20050171063A1 (en) * | 2003-10-20 | 2005-08-04 | Pawan Malhotra | Use of phosphono derivatives as anti-malarials |
US20050090480A1 (en) * | 2003-10-22 | 2005-04-28 | Council Of Scientific & Industrial Research | Use of selected amino acid-zinc complexes as anti-malarials |
US20140322240A1 (en) * | 2011-11-22 | 2014-10-30 | The University Court Of The University Of Edinburg | Malaria vaccine |
JP2017512498A (ja) * | 2014-03-28 | 2017-05-25 | フラウンホーファーゲゼルシャフト ツール フォルデルング デル アンゲヴァンテン フォルシユング エー.フアー. | 複数成分複数段階マラリアワクチン |
Non-Patent Citations (1)
Title |
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CHEN, Jun-Hu et al. Growth-inhibitory effect of a fucoidan from brown seaweed Undaria pinnatifida on Plasmodium parasites. Parasitology Research. 2009, vol. 104, pp. 245-250. See abstract and pages 247-249. X 1,7 Y 2-6,8-12 * |
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