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WO2007066991A1 - Composition comprenant un extrait de celosie, destinee a la prevention et au traitement de maladies humaines causees par differents virus - Google Patents

Composition comprenant un extrait de celosie, destinee a la prevention et au traitement de maladies humaines causees par differents virus Download PDF

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WO2007066991A1
WO2007066991A1 PCT/KR2006/005280 KR2006005280W WO2007066991A1 WO 2007066991 A1 WO2007066991 A1 WO 2007066991A1 KR 2006005280 W KR2006005280 W KR 2006005280W WO 2007066991 A1 WO2007066991 A1 WO 2007066991A1
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virus
extract
family
health food
pharmaceutical composition
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Chang Seon Song
Chi Ung Moon
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Priority claimed from KR1020060123445A external-priority patent/KR100881035B1/ko
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    • 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)
    • A61K36/21—Amaranthaceae (Amaranth family), e.g. pigweed, rockwort or globe amaranth
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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
    • 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
    • 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 an extract of cockscomb for preventing and treating human disease caused by viruses and the use thereof.
  • Influenza has been a major cause of morbidity in human and of mortality in the elderly and infant.
  • Influenza viruses are members of the family Orthomyxoviridae, which is composed of four genera, i.e., influenza virus A, B, C and Thogotovirus.
  • viruses There are 144 kinds of viruses according to their serotypes including 16HA proteins and 9 NA proteins. HA makes virus adhere to a somatic cell and NA makes virus penetrate to intra-cell (Alexander DJ. Vet. Microbiol, 74(1-2), pp3-13, 2000).
  • Avian flu classified into influenza A is caused by avian viral infection mediated by poultries such as chick, duck, turkey, wild avian and the like on farms and in live markets.
  • highly pathogenic avian influenza has been designated as the 1 st group of legal communicable disease in Korea and List A infections disease in OIE (Office International des Epizooties).
  • the pathogen, i.e., avian influenza virus, a sort of zoonotic virus is classified into highly pathogen, weakly pathogenic and nonpathogenic virus according to their pathogenecity.
  • Avian influenza virus is frequently transmitted to human through intermediate host such as swine, chicken, etc, modified by genetic mutation in the host and the mutated virus is transmitted to human through respiratory tract and other pathway resulting in pathogenic avian flu.
  • Newcastle disease virus is a typical paramyxovirus which causes a severe respiratory infection in poultry. This disease is of great economic important, requiring control by vaccination or quarantine with slaughter of all birds in confirmed outbreaks.
  • the genome of NDV is a single strand of RNA of negative polarity.
  • On the outer surface of the viral envelope are the two viral glycoproteins, the haemagglutinin-neu- raminidase HN involved in the binding of the virus to host cell and the fusion protein F involved in fusion with and penetration through the membranes.
  • NDV is a disease of poultry caused by a virus of avian
  • paramyxovirus serotype 1 which has an intracerebral pathogenicity index (ICPI) in day-old chicks of 0.7 or greater.
  • ICPI intracerebral pathogenicity index
  • the poultry is reared or kept in captivity for breeding, the production of meat or eggs for consumption, or for restocking supplies of game. It is generally assumed the first outbreaks of NDV occurred in 1926 in Java, Indonesia, and in Newcastle-upon-Tyne, England. It later became clear that other less severe disease were caused by viruses indistinguishable from NDV.
  • IBV Infectious bronchitis virus
  • IB infectious bronchitis
  • the poultry is severely affected by epizootics of this disease.
  • Infectious bronchitis still causes a large mortality, especially with young poultry. Besides the mortality and more or less strong respiratory symptoms, lesions to the oviducts occur and as a result thereof, egg production drops caused by an IB infection occur.
  • infections with IB virus may stimulate latent virus or bacterial infections and may give rise in this way to severe economical losses, especially in the broiler field.
  • the disease continues to be a problem in commercial poultry because some serotypes do not cross protect against antigenically unrelated serotypes including variant strains of the virus (GeIb J. Jr. et al., Avian Dis., 35, pp 82-87, 1991; King D. G.., Avian Dis., 32, pp 362-364, 1988).
  • IBV serotype such as the Massachusetts type, 793B or 4/91
  • Massachusetts type vaccine or 793/B type vaccine has been used since 1990, there still remains a great need for IB vaccines with adequate immunizing properties. It will be appreciated that the desired improvement of these vaccines is still severely hampered due to the immunogenic change and other properties of the presently available IB viruses after a large number of passages in em- bryonated chicken eggs, the appearance of new serotype and the lack of sufficiently applicable serological and immunological test procedures, respectively.
  • Corona virus an aetiological virus of SARS has known to be transferred from
  • Avian pneumovirus a member of the Paramyxoviridae family of viruses, has known to be the etiological agent of turkey rhinotracheitis (TRT), which cause an acute upper respiratory tract infection characterized by coughing, nasal discharge, tracheal rales, foamy conjunctivitis and sinusitis in young poultries.
  • TRT turkey rhinotracheitis
  • PRRSV is an enveloped RNA virus, the viral genome of which comprises a single-stranded RNA of positive polarity. In 1987 it was first detected in North America a swine disease. A very similar syndrome was first detected in Central Europe in 1990, and spread later to other European countries. European type and North American type viruses are clearly different from each other in respect to not only their serological reactivity but also the homology degree of nucleotide sequences of significant RNA fragments.
  • PRRS is one of the most important diseases affecting economic loss on the swine sector through directly and indirectly, which are caused by secondary agents favored by PRRS virus infection.
  • a relatively smaller sized RNA virus called as picona virus belongs to the family piconaviridae.
  • the enterovirus belongs to the family piconaviridae. At present, 71 serotypes among the viruses have known to infect humans.
  • the enterovirus genome is a single- stranded RNA molecule that encodes one large protein, which undergoes auto- catalytic proteolysis into a set of smaller structural and non- structural proteins.
  • Enteroviruses are second to rhinoviruses as the most common viral infection in humans. Enteroviruses enter the body through the alimentary tract and possibly the respiratory route. Their normal site of replication is the gastrointestinal tract, where they typically cause mild GI disorder accompanied by non-specific febrile illness.
  • Typical en- terovirus diseases are meningitis, paralysis, myocarditis, generalized infections in newborns, hand, foot and mouth-disease, herpangina, pleurodynia, hepatitis, rash, exanthemas and respiratory disease including pneumonia. Accordingly, there has been needed in the art to improve the ability to diagnose rapidly and accurately enterovirus infection.
  • Coxsackievirus belongs to a group of the genus Enterovirus of the family Pi- cornavidae. It is a spherical (regular icosahedron), non-enveloped virus with a diameter of about 25 to 30nm. From the antigenicity viewpoint, it is classified into two types (A and B) and each further includes a number of serotypes.
  • Reticuloendotheliosis viruses are the group of serologically related
  • REVs avian leucosis retroviruses
  • REV isolates have been obtained from turkeys, pheasants, chickens and ducks.
  • Representative REVs include strain T (subtype 1), chick syncytial (CS; subtype 3), spleen necrosis (SN; subtype 2), and duck infectious anemia (DIA; subtype 2) viruses.
  • a single replication-defective, acutely transforming REV isolate is known as REV-T, which carries the rel oncogene and which requires a non-defective helper virus (such as strain REV-A) for replication.
  • REV-T causes an acute reticulum cell neoplasia in inoculated chickens.
  • the virus has a large DNA molecule with numerous non-essential regions that allow the insertion of several immunogenic genes into the same virus for the purpose of developing multivalent vaccines. These multivalent vaccines may induce cell-mediated as well as antibody-mediated immune response in a vaccinated host.
  • No vaccine against REV is currently available.
  • REV consists of 1 stranded RNA however it might be 2-stranded DNA during proliferation sue to RNA dependent DNA polymer enzyme, which further inserted into chromosomal DNA and may be presented as provirus (Fritsch E. et al., Virology, 83, pp313-321, 1977). Because of their characteristics of gene types in host genome during such REV infection, the development and use of live vaccine has been reported to impossible and the preparation of vaccine is also difficult since the glycoprotein 85 (gp 85) reproducing the neutralization antibody against the virus is very unstable.
  • gp 85 glycoprotein 85
  • Aujeszky's disease virus is a highly neurotropic herpesvirus that contami nates domestic and wild animals (Thowley DG et al., J. AM. Vet. Med. Assoc, 176, pplOOl-1003, 1980). Pigs are relatively resistant against PRV therefore they are considered as the natural host of the virus. The virus is able to replicate by itself in the cell of the nasal and pharyngeal mucosa, and after the infection of peripheral nerves, it is transported to the central nervous system resulting in severe encephalitis which is often fatal to young pigs. Older pigs usually survive the infection, but may develop fever and pneumonia. Infection in sensory ganglia generally results in the establishment of latency. Vaccination against Aujeszky s disease is carried out to reduce the economic damage caused by mortality and growth retardation in infected animals (Lee JB et al., Korean J. Vet. Res., 28(1), pp99-103, 1988).
  • Ads Human adenovirus
  • ITR inverted terminal repetitions
  • Cockscomb has been used as a flower bed and there are 60 species in tropical zone and subtropical zone such as America, Asia, and Africa. Celosia cristata showing round or crest shape, Celosia plummosa, Celosia argentea widely distributed in Korea, and the other crossing species have been known till now. Celosia argentea has been used for medicinal purposes and Chinese medicine. There has been known that the extract of the celosia comprises 10% of oxalic acid and the seed of Celosia collected in August to October comprises fatty oils, abundant potassium sulfate and nicotinic acid (Lee CB, Illustrated flora of Korea, p321, 1999).
  • cockscomb extract shows potent inhibiting activity of various viruses.
  • the present invention provides a pharmaceutical composition and a health food comprising an extract of cockscomb as an active ingredient in an effective amount to treat and prevent the diseases caused by the infection of virus in human.
  • the present invention also provides a use of an extract of cockscomb showing antiviral activity.
  • the present invention also provides a method for treating or preventing the diseases caused by the infection of virus in human comprising administering to said human an effective amount of an extract of cockscomb together with a pharmaceutically acceptable carrier thereof.
  • extract comprises the crude extract and non-polar solvent extract of cockscomb.
  • C 1 -C 4 lower alcohols such as methanol, ethanol, preferably methanol and the like, or the mixtures thereof, preferably ethanol.
  • non-polar solvent soluble extract can be prepared by extracting the above described crude extract with non-polar solvent, for example, hexane, ethyl acetate, dichloromethane, or chloroform, preferably dichloromethane.
  • non-polar solvent for example, hexane, ethyl acetate, dichloromethane, or chloroform, preferably dichloromethane.
  • Clarkescomb disclosed herein comprises the Celosia argentea, Celosia plummosa, Celosia cristata and the like.
  • virus disclosed herein comprises RNA type virus or DNA type virus.
  • RNA type virus comprises influenza virus, Newcastle disease virus, infectious bronchitis virus, avian pneumovirus, porcine reproductive and respiratory syndrome virus, coxsakie virus or reticuloendotheliosis virus.
  • influenza virus disclosed herein comprises HlNl, H9N2 or H6N5
  • DNA type virus disclosed herein comprises Aujeszky's disease virus or adeno virus.
  • virus comprises orthomyxo virus family including influenza virus; paramyxo virus family including Newcastle disease virus; corona virus family including infectious bronchitis virus; picorna virus family including Coxsakie virus; retrovirus family including reticuloendotheliosis virus; herpes virus family including Aujeszky's disease virus; or adenovirus family including adeno virus.
  • viral disease caused by the internal infection of influenza virus family comprises common cold, influenza, avian flu or variant infectious avian flu.
  • viral disease caused by the internal infection of paramyxo virus family comprises Parainfluenza, Mumps, Measles, Nipah virus, Hendra virus, Respiratory syncytial virus or Human me tapneumo virus.
  • HCoV-229E Severe Acute Respiratory Syndrome (SARS) or HCoV-OC43.
  • SARS Severe Acute Respiratory Syndrome
  • viral disease caused by the internal infection of picornavirus family comprises Encephalomyocarditis virus, Poliovirus, Coxsackievirus, Echovirus, Rhinovirus, Parecovirus or Hepatitis A virus.
  • human immunodeficiency virus type 1 & 2 or human foamy virus comprises human immunodeficiency virus type 1 & 2 or human foamy virus.
  • herpesvirus family comprises herpes simplex virus, Epstein-barr virus, cytomegalovirus, varicella-zoster virus, human herpesvirus 6, 6A, 6B, 7, kaposi's sarcoma or cerco- pithecine herpesvirus.
  • viral disease caused by the internal infection of adeno virus family comprises respiratory infection, gastroenteritis, Epidemic keratoconjunctivitis, Hemorrhagic cystitis or Meningitis in human.
  • a method for treating or preventing the diseases caused by the infection of virus in human comprising administering a therapeutically effective amount of an extract of cockscomb into the human suffering with virus disease.
  • An inventive extract isolated from of cockscomb may be prepared in accordance with the following preferred embodiment.
  • the dried whole plant of cockscomb is cut into small pieces and the piece was mixed with 1 to 30-fold, preferably, 1 to 15-fold volume of polar solvent, for example, water, C -C lower alcohol such as methanol, ethanol, butanol, or the mixtures thereof, preferably ethanol; and is heated at the temperature ranging from 10 to 100 0 C, preferably from 20 to 5O 0 C, for the period ranging 1 to 24 hours, preferably 5 to 20 hours, by reflux extraction with hot water, cold water extraction, ultra- sonication or conventional extraction, preferably by reflux extraction or hot water; the residue was filtered and then the filtrate is dried by vacuum freeze-drying to obtain the crude extract of the present invention.
  • polar solvent for example, water, C -C lower alcohol such as methanol, ethanol, butanol, or the mixtures thereof, preferably ethanol
  • Remaining polar solvent soluble layer is collected by removing the non-polar solvent soluble extract to obtain polar solvent soluble extract of the present invention which may be soluble in water, lower alcohols such as butanol, or the mixtures thereof.
  • composition comprising a crude extract or non-polar solvent soluble extract of cockscomb prepared by the above-described preparation method for the treatment and prevention of the diseases caused by the infection of virus in human.
  • a method for treating or preventing the diseases caused by the infection of virus in human comprises administering a therapeutically effective amount of a crude extract or non-polar solvent soluble extract of cockscomb prepared by the above-described preparation method into the human suffering with the diseases caused by the infection of virus in human.
  • the inventive composition for treating and virus disease may comprise the above described extract as 0.1 ⁇ 50% by weight based on the total weight of the composition.
  • inventive composition may additionally comprise conventional carrier,
  • adjuvants or diluents in accordance with a using method well known in the art. It is preferable that said carrier is used as appropriate substance according to the usage and application method, but it is not limited. Appropriate diluents are listed in the written text of Remington's Pharmaceutical Science (Mack Publishing co, Easton PA).
  • composition according to the present invention can be provided as a pharmaceutical composition containing pharmaceutically acceptable carriers, adjuvants or diluents, e.g., lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starches, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinyl pyrrolidone, water, methylhydroxy benzoate,
  • pharmaceutically acceptable carriers e.g., lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starches, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinyl pyrrolidone, water, methylhydroxy benzoate,
  • compositions of the invention may be formulated so as to provide quick, sustained or delayed release of the active ingredient after their administration to a patient by employing any of the procedures well known in the art.
  • compositions of the present invention can be dissolved in oils, propylene glycol or other solvents that are commonly used to produce an injection.
  • suitable examples of the carriers include physiological saline, polyethylene glycol, ethanol, vegetable oils, isopropyl myristate, etc., but are not limited to them.
  • the extract of the present invention can be formulated in the form of ointments and creams.
  • compositions containing present composition may be prepared in any form, such as oral dosage form (powder, tablet, capsule, soft capsule, aqueous medicine, syrup, elixirs pill, powder, sachet, granule), or topical preparation (cream, ointment, lotion, gel, balm, patch, paste, spray solution, aerosol and the like), or injectable preparation (solution, suspension, emulsion).
  • oral dosage form prowder, tablet, capsule, soft capsule, aqueous medicine, syrup, elixirs pill, powder, sachet, granule
  • topical preparation cream, ointment, lotion, gel, balm, patch, paste, spray solution, aerosol and the like
  • injectable preparation solution, suspension, emulsion
  • composition of the present invention in pharmaceutical dosage forms may be used in the form of their pharmaceutically acceptable salts, and also may be used alone or in appropriate association, as well as in combination with other pharmaceutically active ingredients.
  • the desirable dose of the inventive composition varies depending on the condition and the weight of the subject, severity, drug form, route and period of administration, and may be chosen by those skilled in the art. However, in order to obtain desirable effects, it is generally recommended to administer at the amount ranging from 0.001 to 100mg/kg, preferably, 0.1 to 100mg/kg by weight/day of the inventive extract of the present invention. The dose may be administered in single or divided into several times per day.
  • composition therein can be added to food, additive or
  • the amount of the above described extract in food or beverage may generally range from about 0.01 to 95w%, preferably 1 to 80w% of total weight of food for the health care food composition.
  • the present invention provides a composition of the health care beverage
  • examples of addable food comprising the above- described extract of the present invention are various food, beverage, gum, vitamin complex, health improving food and the like, and can be used as powder, granule, tablet, chewing tablet, capsule or beverage etc.
  • composition of the present invention has no toxicity and adverse effect therefore they can be used with safe.
  • the above-described composition therein can be added to food, additive or beverage, wherein, the amount of the above-described extract in food or beverage may generally range from about 0.01 to 80w/w%, preferably 0.01 to 15w/w% of total weight of food for the health food composition and 0.02 to 5g, preferably 0.3 to Ig on the ratio of 100ml of the health care beverage composition.
  • the health care beverage composition of present invention contains the above-described extract as an essential component in the indicated ratio
  • the other liquid component wherein the other component can be various deodorant or natural carbohydrate etc such as conventional beverage.
  • Examples of aforementioned natural carbohydrate are monosaccharide such as glucose, fructose etc; disaccharide such as maltose, sucrose etc; conventional sugar such as dextrin, cyclodextrin; and sugar alcohol such as xylitol, and erythritol etc.
  • natural deodorant such as taumatin, stevia extract such as levaudioside A, glycyrrhizin et al., and synthetic deodorant such as saccharin, aspartam et al., may be useful favorably.
  • the amount of above described natural carbohydrate is generally ranges from about 1 to 20 g, preferably 5 to 12 g in the ratio of 100 D of present beverage composition.
  • the other components than aforementioned composition are various nutrients, a vitamin, a mineral or an electrolyte, synthetic flavoring agent, a coloring agent and improving agent in case of cheese chocolate et al., pectic acid and the salt thereof, alginic acid and the salt thereof, organic acid, protective colloidal adhesive, pH controlling agent, stabilizer, a preservative, glycerin, alcohol, carbonizing agent used in carbonate beverage et al.
  • the other component than aforementioned ones may be fruit juice for preparing natural fruit juice, fruit juice beverage and vegetable beverage, wherein the component can be used independently or in combination.
  • the ratio of the components is not so important but is generally range from about 0 to 20 w/w % per 100 w/w % present composition.
  • Examples of addable food comprising aforementioned extract therein are various food, beverage, gum, vitamin complex, health improving food and the like.
  • the present invention provides a pharmaceutical composition and a health food comprising an extract of cockscomb as an active ingredient in an effective amount to treat and prevent the diseases caused by the infection of virus in human.
  • Fig. 1 shows the anti viral activity of the 60% ethanol extract of cockscomb on
  • Fig. 2 presents the anti viral activity of the non-polar solvent soluble extract of cockscomb on MDCK cell causing A/PR/8/34(HlNl) influenza.
  • RNA virus pneumovirus, Porcine reproductive and respiratory syndrome virus, Coxsakie virus and reticuloendotheliosis virus were prepared as a RNA virus.
  • A/PR/8/34(HlNl) strain was obtained from Hokkaido University, A/HS/K5/01 strain was obtained from Kunkuk Veterinary college in Korea, proliferated in the
  • A/HS/MS96/96 isolation strain was obtained from National Veterinary Research and Quarantine Service, proliferated in the 10-day-old SPF egg for 48 hours for in vitro and in vivo experiment, and left at -8O 0 C.
  • NDV Newcastle disease virus
  • M41 strain were obtained from National Veterinary Research and Quarantine
  • ATCC VR-2332 parental virus strain of the PRRSV Ingelvac®PRRS modified live vaccine was obtained from National Veterinary Research and Quarantine Service, proliferated in MARK- 145 cell, and left at -8O 0 C.
  • Chicken syncytial virus(CSV) was obtained from ATCC, proliferated in chicken embryo fibroblast cell, and left at -8O 0 C.
  • Aujeszky's disease virus and Adeno virus were prepared as a DNA virus.
  • Aujeszky's disease virus was obtained from National Veterinary Research and
  • Quarantine Service proliferated in Hep-2 cell, and left at -8O 0 C.
  • Adeno virus was obtained from Korea National Institute of Health in Korea, proliferated in Hep-2 cell, and left at -8O 0 C.
  • MDCK cell American Type Culture Collection, Manassas, VA, USA
  • EMEM Eagle's minimum essential medium
  • MEM Minimum essential medium
  • Hep-2 cell was obtained from Korea Research Institute of Chemical Technology
  • MARK-145 cell was obtained from National Veterinary Research and Quarantine
  • sample was diluted with 100-fold in distilled water and the diluted extract was further diluted with 1000-fold, 2000-fold, 4000-fold, 8000-fold,
  • the cells were prepared by the incubation to proliferate into monolayer on 96 well plates. 25D of the mixture was inoculated in various dilutions, i.e., un-diluted solution, 10 "1 , 10 "2 , 10 "3 , 10 “4 , 10 "5 and 10 ⁇ 6 diluted solution on 8 well/dilution. 30min after the change of medium, the medium was cultured for 3 to 4 days at 37 0 C in 5% CO and 95% air condition in a humidified incubator. The cytopathic effects (CPE) of virus were determined using by inverted phase microscope.
  • CPE cytopathic effects
  • the virus did not show the cytophatic effect in cell i.e., H9N2 influenza virus and infectious broncheitis virus
  • 0.2ml of the mixture was inoculated into 10-day-old SPF. 3 days after the inoculation, the hemagglutination test and dot immunoassay were performed. The amount of virus was calculated using by Karber method (Payment P et al., Methods and Techniques in Virology, p 33, 1993)
  • extract and fractions of cockscomb were diluted in order to reach at the final concentration of 1000, 320, 100, 32, 10, 3.2, 1, and 0.1 microgram/ml.
  • the effective concentration and cytotoxicity of two fractions per one plate were repeatedly measured by using 96 well plates (greiner, Germany). To determine the effective concentration, 100 TCID /100D/well of virus was inoculated into the monolayer on 96 well plates divided
  • n-butanol soluble layer was concentrated by rotary evaporator and dried with freeze dryer to obtain 7.354g of n-butanol soluble extract and 61.59g of water soluble extract.
  • Example 1-2 To determine the antiviral activity of the extract of cockscomb on various viruses, the 60% ethanol extract of cockscomb prepared in Example 1-2 was diluted with 500-fold in distilled water. 2.5ml of influenza virus solution (HlNl) was mixed with 2.5ml of the diluted extract of pine needle, exactly reacted for 30min with shaking for 10 min intervals at 4 0 C. As a negative control group, distilled water was used instead of the diluted extract of pine needle in experiment. MDCK (Mardin-Darby Canine Kidney, ATCC, USA) cell line derived from dog kidney was used in the experiment.
  • HlNl influenza virus solution
  • MDCK Mardin-Darby Canine Kidney, ATCC, USA
  • the cells were prepared by the incubation to proliferate into monolayer on 96 well plates. 25D of the mixture was inoculated in various dilutions, i.e., un-diluted solution, 10 "1 , 10 "2 , 10 3 , 10 "4 , 10 "5 and 10 ⁇ 6 diluted solution on 8 well/dilution. 30min after the change of medium, the medium was cultured for 3 to 4 days at 37 0 C in 5% CO and 95% air condition in a humidified incubator. The cytopathic effects (CPE) of virus were determined using by inverted phase microscope.
  • CPE cytopathic effects
  • each 30%, 60% and 100% ethanol soluble extract of cockscomb prepared in Example 1-2 was diluted to 100-fold with distilled water and the diluted extract was further diluted to 1000-fold, 2000-fold, 4000-fold, 8000-fold, 16000-fold and 32000-fold serially.
  • 2.5ml of diluted solution with influenza virus (HlNl) was mixed with 2.5ml of respective diluted extract of cockscomb at the interval of 1 min, exactly reacted for 30min with shaking at the interval of 10 mins at 4 0 C.
  • distilled water was used instead of the diluted sample in experiment.
  • the cells were prepared by the incubation to proliferate into monolayer on 96 well plates. 25D of the mixture was inoculated in various dilutions, i.e., un-diluted solution, 10 "1 , 10 "2 , 10 "3 , 10 “4 , 10 "5 and 10 ⁇ 6 diluted solution on 8 well/dilution. 30min after the change of medium, the medium was cultured for 3 to 4 days at 37 0 C in 5% CO and 95% air condition in a humidified incubator. The cytopathic effects (CPE) of virus were determined using by inverted phase microscope.
  • CPE cytopathic effects
  • the virus did not show the cytophatic effect in cell i.e., H9N2 influenza virus and infectious bronchitis virus
  • 0.2ml of the mixture was inoculated into 10-day-old SPF. 3 days after the inoculation, the haemagglutination test and dot immunoassay were performed. The amount of virus was calculated using by Karber method (Payment P et al., Methods and Techniques in Virology, p 33, 1993).
  • the inhibitory effect of 60% ethanol extract of cockscombon the other viruses such as Newcastle disease virus; chic infectious bronchitis virus; pneumo virus; pig genitalis respiratory syndrome virus; Coxsakie virus; reticuloendotheliosis virus; Aujeszky's disease virus; and adeno virus etc was also determined as follows.
  • argentea was diluted with 100-fold in distilled water and the above extract was diluted with 1000-fold, 2000-fold, 4000-fold, 8000-fold, 16000-fold and 32000-fold and following experiment was performed according to the procedure disclosed in the above Reference Example 4 and the result was shown in Table. 13.
  • virusfREV in chicken embryo fibroblast cell
  • ADV disease virus
  • plaque reduction assay was performed by following procedure disclosed in the above Reference Example 5.
  • each non-polar solvent soluble extract showed potent antiviral effect (%), i.e., 45.5% (dichloromethane soluble extract), 0% (ethyl acetate soluble extract), 0% (n-butanol soluble extract) and 0% (water soluble extract) in the concentration of 100D/ml.
  • dichloromethane soluble extract and water soluble extract of C. argentea showed strong virucidal activity and antiviral activity of A/PR/8/34(HlNl) influenza virus.
  • the non-polar solvent soluble extract of C. argentea prepared from Example 2 was diluted with 100-fold in distilled water and the extract was further diluted with 1000-fold,
  • mice Female SPF BALB/c mouse (Orient, Korea) weighing from 18 to 2 Ig was used and influenza virus A/PR/8/34(HlNl) which causes high death rate and significant clinical signs in mouse was used in the experiment. 50D/mouse of virus solution (Titer: 10 TCID /ml) was nasally inoculated to mouse which was anesthetized.
  • Injection preparation was prepared by dissolving active component, controlling pH to about 7.5 and then filling all the components in 2D ample and sterilizing by conventional injection preparation method.
  • Powder preparation was prepared by mixing above components and filling sealed package.
  • Tablet preparation was prepared by mixing above components and entabletting.
  • Tablet preparation was prepared by mixing above components and filling gelatin capsule by conventional gelatin preparation method.
  • Liquid preparation was prepared by dissolving active component, and then filling all the components in IOOOD ample and sterilizing by conventional liquid preparation method.
  • Vitamin mixture optimum amount
  • Health beverage preparation was prepared by dissolving active component, mixing, stirred at 85 °C for 1 hour, filtered and then filling all the components in IOOOD ample and sterilizing by conventional health beverage preparation method.
  • the extractof cockscomb shown anti-viral effect of influenza A viruses, Newcastle disease virus, infectious bronchitis virus, avian pneumovirus, porcine reproductive and respiratory syndrome virus, Coxsakie virus, reticuloendotheliosis virus, Aujeszky's disease virus, adeno virus and Coxsakie virus in vivo and in vitro. Therefore, it can be used as the therapeutics or functional health food for treating and preventing diseases caused by the viral infection.

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Abstract

La présente invention concerne une composition comprenant un extrait de célosie, destinée à la prévention et au traitement de maladies humaines causée par des virus, et ses applications. L'extrait de célosie de la présente invention a un effet antiviral contre les virus grippaux A, le virus de la maladie de Newcastle, le virus de la bronchite infectieuse, le pneumovirus aviaire, le virus du syndrome dysgénésique et respiratoire du porc, le virus réticuloendothéliose, le virus de la maladie d'Aujeszky, l'adénovirus et le virus Coxsackie in vivo et in vitro. Par conséquent, la composition peut être utilisée comme moyen thérapeutique ou comme aliment santé fonctionnel dans le traitement et la prévention des maladies causées par une infection virale.
PCT/KR2006/005280 2005-12-07 2006-12-07 Composition comprenant un extrait de celosie, destinee a la prevention et au traitement de maladies humaines causees par differents virus Ceased WO2007066991A1 (fr)

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KR20050118469 2005-12-07
KR10-2005-0118469 2005-12-07
KR1020060123445A KR100881035B1 (ko) 2005-12-07 2006-12-07 맨드라미 추출물을 함유하는 바이러스로 인한 인간 질환의치료 및 예방용 조성물
KR10-2006-0123445 2006-12-07

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8017168B2 (en) 2006-11-02 2011-09-13 The Coca-Cola Company High-potency sweetener composition with rubisco protein, rubiscolin, rubiscolin derivatives, ace inhibitory peptides, and combinations thereof, and compositions sweetened therewith
ITMI20101833A1 (it) * 2010-10-08 2012-04-09 Velleja Res Srl Metodo per la preparazione di estratti totali da piante medicinali o alimentari mediante estrazione frazionata
US9101160B2 (en) 2005-11-23 2015-08-11 The Coca-Cola Company Condiments with high-potency sweetener

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GHOLIZADEH A. ET AL.: "Cloning and expression of small cDNA fragment encoding strong antiviral peptide from Celosia cristata in Escherichia coli", BIOCHEMISTRY, vol. 70, no. 9, September 2005 (2005-09-01), MOSCOW, pages 1005 - 1010, XP019294672 *
GHOLIZADEH A. ET AL.: "Modifications in the purification protocol of Celosia cristata antiviral proteins lead to protein that can be N-terminally sequenced", PROTEIN PEPT. LETT., vol. 11, no. 6, 2004, pages 551 - 561, XP008082202 *
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9101160B2 (en) 2005-11-23 2015-08-11 The Coca-Cola Company Condiments with high-potency sweetener
US8017168B2 (en) 2006-11-02 2011-09-13 The Coca-Cola Company High-potency sweetener composition with rubisco protein, rubiscolin, rubiscolin derivatives, ace inhibitory peptides, and combinations thereof, and compositions sweetened therewith
ITMI20101833A1 (it) * 2010-10-08 2012-04-09 Velleja Res Srl Metodo per la preparazione di estratti totali da piante medicinali o alimentari mediante estrazione frazionata

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