WO2015167028A1 - Utilisation de rhemannia glutinosa liboschtz var. purpurea makino brut et/ou séché dans la préparation d'un médicament antiviral - Google Patents
Utilisation de rhemannia glutinosa liboschtz var. purpurea makino brut et/ou séché dans la préparation d'un médicament antiviral Download PDFInfo
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- WO2015167028A1 WO2015167028A1 PCT/KP2015/000038 KP2015000038W WO2015167028A1 WO 2015167028 A1 WO2015167028 A1 WO 2015167028A1 KP 2015000038 W KP2015000038 W KP 2015000038W WO 2015167028 A1 WO2015167028 A1 WO 2015167028A1
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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)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
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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)
- A61K36/80—Scrophulariaceae (Figwort family)
- A61K36/804—Rehmannia
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- 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)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
-
- 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)
- A61K36/85—Verbenaceae (Verbena family)
Definitions
- the present invention relates to the new Use of the Korean Traditional Medicine.
- the present invention has been objected by the use of raw RLM and dried RLM in the preparation of the antiviral medicine for treating the measles, the mumps, the influenza (subtype), the parainfluenza, the hand-foot-mouth disease, the varicella and the herps zoster which is RNA virus or DNA virus infestation.
- Measles, ihe SARS, the HIV, the Ebola hemorrhagic fever and etc. are have been raged throughout the world, and several millions of people are suffered the pain and not a few people are dead.
- influenza and measles that are respiratory epidemic diseases have recorded not a few death due to occur in locally or worldwide, small and large epidemic several times till now.
- the occurrence of the measles and the mumps that are children's acute epidemic diseases have been better reduced by introduction of the vaccine, but it has still suggested as an important subject the children death by the measles for not inventing the effidacious antiviral medicine.
- Tamiflu distributed by Roche Laboratories Inc., is being widely used as antiviral drugs for the treatment of Influenza A and it has been reported that this medicine helps to prevent the infection of virus into organism so that the virus could't be invaded in host cell by causing activity of neuraminidase to inhibit.
- periostracuiri cicadae has taken effect in the treatment of influenza virus (HiNi).
- CN 031250866 it has disclosed that the 17 species extraction including hemp seed, tree peony bark, peach kernel has high effect in the treatment of varicella.
- Acycloguanosine has the selective ⁇ antiviral activity against simple herpes virus including varicella-herpes zoster virus and been widely used in the treatment of varicella-herpes zostei virus infection.
- compositions based on benzophenahthridine alkaloids extracted from hippophae rhamnoides and echinacea angustifolia have high eifect in the treatment of parainfluenza virus.
- the object of invention is to provide the use of the various extracts that contains raw RLM and dried RLM as main component to treat complication that is R Aor DNA virus infection and mixed infection, and the preparation method of such extraction.
- the most common and specific symptoms in the clinical appearance is the febrility and the febrility has the different characteristics according to the epidemic disease.
- the febrility has the diagnosis significance.
- the febrility makes a great change in the body function.
- the febrility makes rapid progress and the time maintained by high febrility is long in the respiratory epidemic disease, Therefore, the febrility, which is the important symptom of the epidemic diseases, has been objected and pharmacological actio of the various CYRH( CHONGYOLRYANGHYOL) medicines (this medicine of which property is cold goes down the febrility by getting off the haematic nosogenesis.) has been used as the main action.
- RLM From earlier ages, RLM have been divided into RRLM, DRLM and SRLM(steamed RLM) according to the preparation method, and so have been used in a wide variety of uses.
- RRLM and DRLM are all CYRH medicines and SRLM has been used as the producing blood medicine.
- RRLM goes down the fever, gets off the blood fever and brings into existence the resin.
- DRLM strengthens with the negative element, brings into existence the blood and removes the blood fever.
- RRLM has been used in the blood fever symptoms, the engorgement symptoms and the lack of the resin, and DRLM has been used in the fever and symptoms due to lack of the negative element and blood.
- the viral infection Before happening the many viral infection, by the response of viral immune reaction, the viral infection can be stopped or gone slightly.
- cytokine that is not an antigen specific in the cell-mediated immunity system that is one of the immune reply system strengthens the immune action.of body, so all viral duplicating course has been impeded by interferon and the course of diseases has been progressed as a slightly illness or recovered and furthermore toxicosis and complication have been impeded.
- RRAM and DRAM has been used for the preparation of antiviral medicine, and the percent of its mass is 50-80% in each.
- This antiviral medicine has been used for the treatment of RNA virus infection, DNA virus infection and its mixed infection of the respiratory tract.
- REAM and DRAM are used as the main component for the preparation of the antiviral medicine.
- RRAM is little sweet, very cold property and highest of the component content.
- the routes operated are the route of heart, the route of kidney, the route of liver and the route of small intestines.
- DRAM is a little bitter and its property is cold.
- the routes operated are the route of heart, the route of kidney, the route of live and the route of small intestines.
- the composition is catapol, mannite, petbarih, polysaccharide, sugar, 11 kinds of amino acid, steroid and flavonoid.
- CYM(CHONGYOL medicine: medicine of which property is cold goes down the fevrility) removes the interior fever and is the traditional medicines treats the interior fever symptoms.
- This medicine gets off the fever in component of the blood, so that it has been used in treating the various kinds of bleeding due to the fever of blood, serious fever and rash due to an invasion of calefaction reason into the nutrition component.
- Arctium lappa 1. is the ripen fruit of arctium lappa 1. belong to compositae, as abiennial grass. It is the PUNGYOLHAPYO medicine (PYHP medicine: gets off the nosogenesis come out in surface due to air and fever by the sweat.). The taste is sharp and the property is comfortable. It removes the air-fever, detoxicates and facilitate an eruption.
- the routes operated are the route of lung and the route of stomach.
- the main component is the arctinin that is the lignin glycoside.
- the antifebrile and antidote As it is the antifebrile and antidote, so it has been used for pneumonia, bronchitis, measles, laryngitis and tonsillitis when it gets a fever, a cough and a difficulty in breathing due to the influenza.
- a cast-off skin of a cryptotympana coreana or a horse cicada belong to cicadidae is used.
- a cast-off skin of a cicada is a cast-off skin that casts its skin when the larvaes come out of the ground and become the imagoes.
- the taste is sweet, salty and the property is cool.
- the routes operated are the route of lung and liver;
- cimicifuga heracleifolia komar belong to ranunculaceae, it is to be dried its root(the color of snow cimicifuga heracleifolia komar).
- the taste is sweet, the property is common and the routes operated are the rout of stomach, the route of colon and lungs.
- Fructus v3 ⁇ 4icis belongs to verbenaceae, it is to be dried the ripened fruits of vitex rotundifolia 1. in the sun.
- the taste is bitter, sharp and the property is little cool.
- the route operated is the route of bladder. It diffuses the Air-Fever, makes eye brighter and kills an intestinal worm.
- RRAM has been used, it harvested in late aiitumn and kept into the humid sand by washing or like that lest the component contents should be not changed.
- 3-5mm of cut DRAM should be dried in a cool place so that the humidity content is less than 13% and ash Content is less than 5%.
- RAM have been cut off to straight or inclination direction, arctium have been roasted and the arms and legs of cast-off skin of a cicada have been taken off.
- Cimicifuga heracleifolia komar has been used, is to be dried its root.
- Fructus viticis has been used, is to be dried the ripened f uits of vifex rotundifolia 1. in the sun. After mixing the above medicines* grinding, filling water at the rate of 1 :5-10, extracting three times per every two hours in 80-90 ° C of the temperature, and concentrating, filtering, diluting by distilled ater, packaging, sterilizing it.
- the measles virus(edminston) strains of 100TCID50/0.05 mfi has been implanted in the culture of the pulmonary circulation cell strain, and then this medicine has been implanted after a hour and the cytopathic effect has been observed.
- the compound extract of RAM, arctium and cast-off skin of a cicada and of RAM and cast-off skin of a cicada have inhibited the cell degeneration even in diluted solution of 1 :500.
- HsNitype virus The incubating period is about H)- 11 days
- Method for experiments the viral undiluted solution was cultivated by implanting virus in paravesical pouch of incubated egg of 11 days have been diluted up to l(T 3 -lCr 8 by decimalizing, and implanted its 0.1 mi to the paravesical pouch of 3 incubated eggs per a diluted liquid, and then it have been cultivated for 24 hours in an incubator of 37 ° C. After that, the titer have been estimated by auto hemagglutinative reaction and the number of inhibition zone has been calculated by Reed and Muench method.
- the number of inhibition zone of the extraction of RAM and cast-off skin of cicada for H5N1 Type virus was 3.85.
- the number of inhibition zone of the present medicine for HiNi Type virus is 3.2.
- the virus have been diluted by the method of decimalizing and the infection titer have been measured.
- the diluted liquid bylO 4 , 10 3 , 10 2 , CD 50/mfi have been infected in each 5 apertures per dilution multiple.
- the present medicines have been applied at treating of the measles, the influenza(subtype), the parainfluenza, the varicella , the herps zoster, the mumps, and the hand-foot-mouth disease by a popular remedies, so the clinical effect that had observed for more than 50 years is as follows;
- Example 3 use of the present medicines in the measles treatment
- Indication typical type (a slight illness, a serious illness of middle class, a serious illness), non typical type(nonfever, noneruption, noncatarrh, baby measles) and measles complication without regard to age, sex and immune state.
- Stage of all stage including incubating, catarrh eruption, extinction, and catabasis.
- Subjective symptom cutis eruption, ophthalmic congestion, gullet rubor, pulmo finding, disorder of consciousness, experiment assay finding
- Non-change Any change the subjective and objective symptoms of fever, rash, etc.
- Study group- «A»group comprised of 20.9% of person with eruption and 79.1% of person with no-eruption without regard to the attack days.
- Control group, 1 group- «B»group comprised of 14% pf person ith eruption and 86% of
- Control group 2 group- «C»group comprised of 100% of person with no'-eruption, wherein treatment according to the popular remedies that have been applied.
- the measles is a disease of which infectiousness is violent, it is the acute eruptive child epidemic disease having fever, upper airway catarrh symptom, and a characteristic eruption of the oral cavity and the skill.
- the infection source is only a patient. Patient has the infectiousness from the end of incubating stage to 5 days after eruption. A period of the strongest infectiousness is the catarrh time of first
- the medicines according to the present invention the extract of 50-80% of DRLM and 20-50% of cast-off skin of a cicada
- o «A»group the " extract of 5Q-80% of DRLM and 20-50% of cast-off skin of a cicada o «C»group: popular remedies; the extract of 50-80% of cimicifuga heracleifolia komaf, 10-30% of arrowroots, 5-10% of radix paeoniae albae and 5-10% of licorice Dosage: in the case of an adult, two times a day, 200 m£/each time after a meal.
- p «C»group Normal fever; 0 %, effective rate; 0 %
- o «A»group First eruption rate; 79.7%, 70% of person among the no-eruption patients.
- o «C»group any reaction in the catarrh time and it showed the toxicosis. 77.1 % of high fever patients and the removal fever day was about 4.0.
- o «A»group Normal fever; 90.5%, effective rate; 99.1%
- o «B»group Normal fever; 0 %, effective rate; 0 %
- o «A»group First eruption rate; 92.3%, the fever of the reminder of no-eruption patients fell down and they Were all the vaccinees, slight-passed ones. The eruption parts were the neck, forehead and back and its color Was light pink and its size was like the size of hulled millet. Its number was about 3-5-7.
- o «B»group The first eruption rate; 0% o « A»group: The fever fell down and the eruption came out and finished in the catarrh time for 92.3% of patients and it recovered slightly without any toxicosis.
- the applied medicine the extract of 50-80% of DRLM and 20-40% of Arctium and
- o «A»group Normal fever; 89%, effective rate; 100%
- o «B»group Normal fever; 0 %, effective rate; 0 %
- the applied medicine the extract of 15-25% f DRLM, 15-25% of RRLM, 20-30% of
- o «A»group the extract of 15-25% of DRLM, 15-25% of RRLM, 20-30% of Arctium and 10-20% of cast-off skin of a cicada
- o «B»group antibiotic medicine, a roe deer's blood as the treatment according to the symptoms
- o «A»group Normal fever; 75.3%, effective rate; 100%,
- the applied medicine the extract of 50-80% of DRLM, 10-30% of Arctium and 10-20% of cast-off skin of a cicada
- o «A»group the extract of 50-80% of DRLM, 10-30% of Arctium and 10-20%, of cast-off skin of a cicada
- o «A»group Normal fever; 9-5.2%, effective rate; 100%
- o «B»group 100% of no change, 0% of extinction.
- the applied medicine the extract of 20-60% of RRLM, 20-60% of DRLM, 10-30% of cast-off skin of a cicada and 10-30% of Fructus Viticis
- Example 4 The use of the present medicine in the treatment of Influenza A (subtype) When the Influenza A (subtype) have been prevailed due to world epidemicity many years in some boundary region of our country, the present medicines have been applied to the patients and the clinical study results are as follows;
- Its pathogen is the kind of RN A virus that belongs to Orthomyxo viridae.
- the clinical type was simple, bronchitis and toxicosis.
- the complication symptoms was bronchitis and pneumonia.
- the apphed medicine the extract of 0-60% of DRLM, 20-30% of Arctium and -
- o «A»group the extract of 50-80% of DRLM, 10-30% of Arctium and 10-20% of
- o «B»group Normal fever; 17.2%, effective rate; 39.2%, average removal fever time; 28.7 hours, reaction person; 16.6%
- o «A»group vomiting immediately effective rate; 4.9%, o «B»group: effective rate; 26.4%, o «A»group: the average removal fever time is 15.4' hours, reaction person is 98.6% and the toxicosis with the removal fever disappeared,
- the applied medicine the extract of 40-60% of LM, 40-60% of DRLM, 20-30% of Arctium and 10-20% of cast-off skin of a cicada
- o «A»group Normal fever; 94.0%, effective rate; 100%, average removal fever time; 15.7 hours, reaction person; 100%
- o «B»group Normal fever; 12.5%, effective rate; 25%, average removal fever time; 24 hours, reaction person; 6.0%
- o «C»group Normal fever; 0%, effective rate; 14.6%, reaction person; 0%
- o «B»group effective rate;, 15.0%
- o «B»group effective rate; 32.0%
- Example 5 The use of the present medicine in the treatment of varicella
- Its pathogen is, the kind of PNA virus, varicella-herpes zoster virus that belongs to
- Observation method Isolated patient in one's house and observed more than two times a day by going and seeing.
- Non-change; non-change, toxicosis the eruption stage have been more progressed and the proper stage of the disease have been passed.
- the applied medicine The extract of 30-60% of DRLM, 20-30% of Arctium and
- o «A»group Normal fever within 24 hours; 73.4%, effective rate; 96.8%, reaction person during 3 days; 100%, average removal fever time; 24 hours
- non-progressing is 79.0%, new eschar formation was 100% and effective rate was 100%, the stage was shortened at 92.0%.
- Example 6 The use of the present medicine in the treatment of mumps
- RNA virus that belongs to Paramixoviridae.
- Clinical type typical mild type, nerve type, complication(hyposialadenitis)
- the applied medicine The extract of 30-60% of RRLM, 30-60% of DRLM, 20-30% of
- o «A»group effective rate within 24 hours; 83.3%, average removal fever time; 12 hours o «B»group: effective rate within 24 hours; 0%, average removal fever time; 8.08 days
- o «B»group about 100% as 83'.0% of hyposialadenitis and l6 d% of sublinguitis
- Its pathogen is- RN A virus that belongs to Paramixoviridae.
- the present medicines have been applied to the twb-three years old children under 5 years of age.
- Attack object was attack 1 ⁇ 3 days as 32.9% of attack 1 days, 27.5% of attack 2 days and 19.33% of attack 3 days.
- the fever type was high as 38-3$.9"C of the fever was 46.9%.
- the applied medicine the extract of 30-60% of RRLM, 30-60% of DRLM, 20-30% of
- o «B»group recovered one; 1 .6%, effective rate; 10.7%, non change; 56.0%, gone from bad to worse ⁇ 33.3%, average removal fever tirne; 4.64 days
- Its pathogen is, the kind of DNA virus, varicella-herpes zoster virus that belongs to
- Ganalioii distinguishing; one- five units of ganalion affection in the part of hemihyper nervus trigeminus, intercostals nerves and nervus ischiadicus, hip, face and back o f ear
- the applied medicine the extract of 30-60% of RRLM, 30-60% of DRLM, 20-30% of arctiurh and 10-20% of cast-off skin of a cicada
- o «A»group effective rate( within 24 hours); 63.0%
- P «B»group effective rate( within 24 hours); 0%
- Its pathogen is, the kind of DNA virus, coxsackievirus and enterovirus 71 type.
- the applied medicine the extract of 30-60% of RRLM, 20-30% of DRLM, 20-30% of
- the disease is the mixed infection of RNA and DNA virus by respiratory tract.
- the applied medicine the extract of 30-60% of RRLM, 20-30% of DRLM, 20-30% of arctium and 10-20% of cast-off skin of a cicada
- Varicella has been appeared in a younger brother and although the third eruption stage has been passed till attack 6 days, 38-39 ° C of the fever has been continued.
- the treatment has been t ⁇ ken as the injection of the antibiotic medicine, but swelling of glandula parotidea of left and right side has been began in attack 9, 10 days and 39 "C of the fever continued and the swelling stage progressed.
- the present medicine by twice a day have been applied on the third day of the swelling stage in 39.2 ° C of the fever.
- the removal fever progressed within 12 hours and all symptoms have been disappeared after 2 days.
- the glandula submandibularis swelling showed only on the left side.
- varicella has beeii appeared in an elder brother and 38 ° C of the fever showed during 5 days and the vesicular was the impetigo state and swelling of glandula parotidea of left and right side has been began on the attack 5 days in the second eruption state;
- the treatment effect of the present medicine was high for the measles, the influenza A(subway), the varicella-herpes zoster arid the hand- foot-mouth disease and any secondary reaction showed.
- the removal fever effect oh the fever that Was the typical symptoms of this diseases was clear and the average removal fever time was less than 24 hours and the effective rate of the subjective symptoms, upper airway catarrh symptom and objective symptoms was more than 95%.
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Abstract
La présente invention concerne l'utilisation récente de Rhemannia glutinosa Liboschtz var. purpurea Makino brut et/ou séché pour préparer un médicament antiviral. Ce médicament antiviral peut traiter une infection virale des voies respiratoires, en particulier la rougeole, les oreillons, la grippe A (sous-type), une para-influenza, la maladie pieds-mains-bouche, la varicelle ou le zona.
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CN107929503A (zh) * | 2017-12-15 | 2018-04-20 | 曲敬来 | 一种治疗病毒感染性疾病的中药组合物及其制备方法 |
CN108096386A (zh) * | 2017-12-31 | 2018-06-01 | 长沙善道新材料科技有限公司 | 一种牛羊用抗口蹄疫病毒的药剂及其制备和使用方法 |
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