WO2022124934A1 - Inhibiting expression of atherogenic microrna-24 and microrna-125 and inducing expression of anti-atherogenic microrna-126, microrna-222 and microrna-let7b - Google Patents
Inhibiting expression of atherogenic microrna-24 and microrna-125 and inducing expression of anti-atherogenic microrna-126, microrna-222 and microrna-let7b Download PDFInfo
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- 230000000923 atherogenic effect Effects 0.000 title claims abstract description 16
- 230000000489 anti-atherogenic effect Effects 0.000 title claims abstract description 14
- 230000001939 inductive effect Effects 0.000 title claims abstract description 5
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 5
- 239000002679 microRNA Substances 0.000 claims abstract description 25
- 235000001287 Guettarda speciosa Nutrition 0.000 claims abstract description 24
- 108700011259 MicroRNAs Proteins 0.000 claims abstract description 19
- 210000002381 plasma Anatomy 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 4
- 239000006286 aqueous extract Substances 0.000 claims description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 3
- 239000000243 solution Substances 0.000 claims description 3
- 239000012153 distilled water Substances 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 239000006228 supernatant Substances 0.000 claims description 2
- 244000061520 Angelica archangelica Species 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 2
- 239000007864 aqueous solution Substances 0.000 claims 1
- 241000125175 Angelica Species 0.000 abstract description 24
- 239000000284 extract Substances 0.000 abstract description 17
- 230000037396 body weight Effects 0.000 abstract description 4
- 230000001973 epigenetic effect Effects 0.000 abstract description 3
- 239000003795 chemical substances by application Substances 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 230000037406 food intake Effects 0.000 abstract 2
- 108091070501 miRNA Proteins 0.000 description 11
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 108091007423 let-7b Proteins 0.000 description 2
- 102000008089 Myosin-Light-Chain Kinase Human genes 0.000 description 1
- 108010074596 Myosin-Light-Chain Kinase Proteins 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 102000000568 rho-Associated Kinases Human genes 0.000 description 1
- 108010041788 rho-Associated Kinases Proteins 0.000 description 1
- 230000009759 skin aging Effects 0.000 description 1
- 210000001626 skin fibroblast Anatomy 0.000 description 1
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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)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D11/00—Solvent extraction
- B01D11/02—Solvent extraction of solids
Definitions
- the invention relates to the field of clinical medicine, namely to the possibility of influencing the expression profile of certain microRNAs in human blood plasma by taking angelica extract, which will make it possible to use angelica extract in the future as a protective agent against the action of certain epigenetic atherogenic factors in human blood plasma.
- the technical result of the claimed method is the possibility of influencing the expression profile of certain miRNAs (miRNA-24, -125, -126, -222, -let7b) in blood plasma by inhibiting the expression of atherogenic microRNAs (miRNA-24, -125) and inducing the expression of antiatherogenic miRNA (miRNA-126, -222, -let7b) by taking angelica extract.
- the above technical result is achieved due to the fact that the method includes the sequential execution of the following steps: 1) obtaining an extract of angelica; 2) taking the resulting angelica extract, 5 drops per 10 kg of body weight daily for 4 weeks.
- An extract of angelica is obtained by drying the roots of the angelica plant for a week at a temperature of 24 ⁇ 1 ° C, then the dried roots are crushed to a powder, then 100 ml of crushed angelica are added to 100 ml of distilled water, stirred, then the resulting mixture is boiled in a water bath for 1-3 hours, until the volume of liquid decreases by 10 times, it is centrifuged at 15,000 rpm for 30 minutes at a temperature of 24 ⁇ 1 ° C, then the resulting supernatant is filtered on a Whatman No.
- miRNAs were isolated from peripheral venous blood (5 ml, collected in a vacuum tube with anticoagulant) using RNeasy Mini Kits (Qiagen, Germany), then reverse transcription was performed using miScript II RT kits (Qiagen, Germany). Germany) and real-time PCR with primers to miRNA-24, 125, 126, 222, let-7b, 16.
- the expression level is given relative to the expression level of miRNA 16 (miRNeasy Mini Kit, miScript II RT Kit, Qiagen, Germany).
- the microRNA values are presented as the ratio of the expression level of the studied microRNA, presented as the number of copies of the studied microRNA/ ⁇ l, to the expression level of the microRNA!
- miRNA copy number 16/ ⁇ l also represented as miRNA copy number 16/ ⁇ l. This approach is generally accepted for reflecting the dynamics of microRNA expression levels, since the expression level of microRNA 16 is stable relative to the expression levels of other microRNAs and can act as a reference, relative to which the expression levels of other microRNAs are evaluated, and the expression levels of microRNAs between different objects (cell lines, cultures, living organisms) can be assessed.
- the level of expression of atherogenic miRNAs in blood plasma after 4 weeks of taking angelica extract at a dosage of 5 drops per 10 kg of body weight decreased: miRNA-24 decreased from 12.1 to 5.4 in a man and from 10.4 to 7.2 in a woman; miRNA-125 from 7.5 to 5.8 in men and from 7.6 to 6.0 in women.
- the level of expression of anti-atherogenic miRNAs in blood plasma after 4 weeks of taking angelica extract increased: miRNA-126 from 4.5 to 5.1 in men and from 5.1 to 6.6 in women; miRNA-222 from 3.8 to 6.7 in men and from 5.8 to 7.1 in women and let-7b from 2.2 to 4.9 in men and from 7.9 to 10.3 in women.
Abstract
Claimed is a method for inhibiting expression of atherogenic microRNA-24 and microRNA-125 and inducing expression of anti-atherogenic microRNA-126, microRNA-222 and microRNA-let7b in human blood plasma. The invention relates to the field of clinical medicine, and more particularly to the possibility of influencing the expression profile of specific microRNA in human blood plasma by ingestion of angelica extract, allowing the future use of angelica extract as an agent for protecting against the effect of specific epigenetic atherogenic factors in human blood plasma. The technical result of the claimed method is that of making it possible to influence the expression profile of specific microRNA (microRNA-24, -125, -126, -222, -let7b) in blood plasma by inhibiting the expression of atherogenic microRNA (microRNA-24, -125) and inducing the expression of anti-atherogenic microRNA (microRNA-126, -222, -let7b) by ingestion of angelica extract. This technical result is achieved in that the claimed method involves successively carrying out the following steps: 1) obtaining angelica extract; 2) ingesting the obtained angelica extract in a daily amount of 5 drops per 10 kg of body weight for a period of 4 weeks.
Description
ИНГИБИРОВАНИЕ ЭКСПРЕССИИ АТЕРОГЕННЫХ МИКРОРНК-24, МИК POP НК -125 И ИНДУЦИРОВАНИЕ ЭКСПРЕССИИ АНТИАТЕРОГЕННЫХ МИКРОРНК- 126, МИКРОРНК -222, МИКРОРНК -LET7B INHIBITION OF EXPRESSION OF ATHEROGENIC MICRORNA-24, MIC POP NK-125 AND INDUCTION OF EXPRESSION OF ANTIATHEROGENIC MICRORNA-126, MICRORNA-222, MICRORNA-LET7B
Изобретение относится к области клинической медицины, а именно к возможности влияния на профиль экспрессии определённых микроРНК в плазме крови человека посредством приема экстракта дудника, что позволит использовать в дальнейшем экстракт дудника в качестве защитного средства от действия определённых эпигенетических атерогенных факторов в плазме крови человека. The invention relates to the field of clinical medicine, namely to the possibility of influencing the expression profile of certain microRNAs in human blood plasma by taking angelica extract, which will make it possible to use angelica extract in the future as a protective agent against the action of certain epigenetic atherogenic factors in human blood plasma.
Из уровня техники известен следующий метод применения экстракта дудника «Средство для предотвращения старения кожи или улучшения состояния её состояния на фоне старения» [US20040223942A1, 6.03.2003, Япония]. Данный метод подразумевает использование экстракта дудника в составе композиции компонентов, влияющих на функциональное состояние фибробластов кожи за счёт повышения экспрессии Rho киназы или киназы лёгкой цепи миозина. Основным отличием данного метода является отсутствие эффекта от применения дудника на эпигенетические атерогенные и антиатерогенные факторы, в частности, на уровень экспрессии в плазме крови атерогенных микроРНК-24, -125 и антиатерогенных микроРНК -126,-222,-let7b. Known from the prior art is the following method of using angelica extract "An agent for preventing skin aging or improving its condition against the background of aging" [US20040223942A1, 6.03.2003, Japan]. This method involves the use of angelica extract as part of a composition of components that affect the functional state of skin fibroblasts by increasing the expression of Rho kinase or myosin light chain kinase. The main difference of this method is the lack of effect from the use of angelica on epigenetic atherogenic and antiatherogenic factors, in particular, on the level of expression in blood plasma of atherogenic microRNA-24, -125 and antiatherogenic miRNA -126, -222, -let7b.
Техническим результатом заявленного способа является возможность влияния на профиль экспрессии определённых микроРНК (микроРНК-24, - 125, -126, -222, -let7b) в плазме крови за счёт ингибирования экспрессии атерогенных микроРНК (микроРНК-24, -125) и индуцирования экспрессии антиатерогенных микроРНК (микроРНК- 126, -222, -let7b) посредством приема экстракта дудника.
Вышеприведённый технический результат достигается благодаря тому, что способ включает последовательное выполнение следующих стадий: 1) получение экстракта дудника; 2) приём полученного экстракта дудника по 5 капель на 10 кг веса ежедневно в течение 4 недель. The technical result of the claimed method is the possibility of influencing the expression profile of certain miRNAs (miRNA-24, -125, -126, -222, -let7b) in blood plasma by inhibiting the expression of atherogenic microRNAs (miRNA-24, -125) and inducing the expression of antiatherogenic miRNA (miRNA-126, -222, -let7b) by taking angelica extract. The above technical result is achieved due to the fact that the method includes the sequential execution of the following steps: 1) obtaining an extract of angelica; 2) taking the resulting angelica extract, 5 drops per 10 kg of body weight daily for 4 weeks.
Получают экстракт дудника путем сушки корней растения дудник в течение недели при температуре 24±1°С, затем измельчают высушенные корни до порошкообразного состояния, далее к 100 г измельчённого дудника добавляют 100 мл дистилированной воды, перемешивают, затем полученную смесь кипятят на водной бане в течение 1-3 часа, до уменьшения объёма жидкости в 10 раз, проводят его центрифугирование при 15000 оборотах/минуту в течение 30 минут при температуре 24±1°С, затем полученный супернатант фильтруют на фильтре Whatman №1, далее раствор концентрируют с помощью роторного испарителя Concentrator plus (Eppendorf) и насоса WP6122050 (Millipore) при следующих условиях: 1400 оборотов/мин., температура 30°С, в течении 16 часов, уровень вакуума 10 мбар. An extract of angelica is obtained by drying the roots of the angelica plant for a week at a temperature of 24 ± 1 ° C, then the dried roots are crushed to a powder, then 100 ml of crushed angelica are added to 100 ml of distilled water, stirred, then the resulting mixture is boiled in a water bath for 1-3 hours, until the volume of liquid decreases by 10 times, it is centrifuged at 15,000 rpm for 30 minutes at a temperature of 24 ± 1 ° C, then the resulting supernatant is filtered on a Whatman No. 1 filter, then the solution is concentrated using a rotary evaporator Concentrator plus (Eppendorf) and pump WP6122050 (Millipore) under the following conditions: 1400 rpm, temperature 30°C, for 16 hours, vacuum level 10 mbar.
Отбирают 5 мл из полученного водного экстракта дудника и разводят 1:5 в физиологическом растворе (0,9 % водном растворе хлорида_натрия) и рекомендуют к приёму per os в объёме 5 капель на каждые 10 кг веса пациента. Take 5 ml from the resulting aqueous extract of angelica and dilute 1:5 in physiological saline (0.9% aqueous sodium chloride solution) and recommend taking per os in a volume of 5 drops for every 10 kg of patient weight.
Пример «Ингибирование экспрессии атерогенных микроРНК-24, -125 и индуцирование экспрессии антиатерогенных микроРНК-126, -222, -let7b по данным исследования микроРНК плазмы крови человека на фоне приёма экстракта дудника ежедневно в течение 4 недель в дозировке 5 капель на 10кг веса». Example "Inhibition of the expression of atherogenic microRNA-24, -125 and induction of expression of anti-atherogenic microRNA-126, -222, -let7b according to the study of microRNA in human blood plasma against the background of taking angelica extract daily for 4 weeks at a dosage of 5 drops per 10 kg of weight."
Мужчина 55 лет 82кг и женщина 43 лет 75кг принимали водный экстракт дудника, приготовленный вышеприведенным способом, ежедневно в течение 4 недель в дозировке 5 капель на 10кг веса. Уровень
экспрессии атерогенных и антиатерогенных микроРНК в плазме крови определяли на 1-ый и на 28-ой день приёма водного экстракта дудника.A 55-year-old man (82 kg) and a 43-year-old woman (75 kg) took an aqueous extract of angelica prepared as described above daily for 4 weeks at a dosage of 5 drops per 10 kg of body weight. Level the expression of atherogenic and anti-atherogenic miRNAs in blood plasma was determined on the 1st and 28th day of taking an aqueous extract of angelica.
Для оценки уровня экспрессии атерогенных и антиатерогенных микроРНК проводили выделение микроРНК из периферической венозной крови (5мл, собрана в вакуумную пробирку с антикоагулянтом) на наборах RNeasy Mini Kit (Qiagen, Германия), затем проводили реакцию обратной транскрипции на наборах miScript II RT kit (Qiagen, Германия) и постановку ПЦР в реальном времени с праймерами к микроРНК- 24, 125, 126, 222, let-7b, 16. Уровень экспрессии приведён относительно уровня экспрессии микроРНК 16 (miRNeasy Mini Kit, miScript II RT Kit, Qiagen, Германия). Значения микроРНК представлены в виде отношения уровня экспрессии исследуемой микроРНК, представленного в виде число копий исследуемой микроРНК/мкл к уровню экспрессии микроРНК! 6, также представленному в виде число копий микроРНК 16/мкл. Данный подход является общепринятым для отражения динамики уровней экспрессии микроРНК, т.к. уровень экспрессии микроРНК 16 является стабильным относительно уровней экспрессии остальных микроРНК и может выступать в качестве референсного, относительного которого оцениваются уровни экспрессии остальных микроРНК и может происходить оценка уровней экспрессии микроРНК между разными объектами (клеточными линиями, культурами, живыми организмами). To assess the level of expression of atherogenic and antiatherogenic miRNAs, miRNAs were isolated from peripheral venous blood (5 ml, collected in a vacuum tube with anticoagulant) using RNeasy Mini Kits (Qiagen, Germany), then reverse transcription was performed using miScript II RT kits (Qiagen, Germany). Germany) and real-time PCR with primers to miRNA-24, 125, 126, 222, let-7b, 16. The expression level is given relative to the expression level of miRNA 16 (miRNeasy Mini Kit, miScript II RT Kit, Qiagen, Germany). The microRNA values are presented as the ratio of the expression level of the studied microRNA, presented as the number of copies of the studied microRNA/µl, to the expression level of the microRNA! 6, also represented as miRNA copy number 16/µl. This approach is generally accepted for reflecting the dynamics of microRNA expression levels, since the expression level of microRNA 16 is stable relative to the expression levels of other microRNAs and can act as a reference, relative to which the expression levels of other microRNAs are evaluated, and the expression levels of microRNAs between different objects (cell lines, cultures, living organisms) can be assessed.
Полученные значения уровней экспрессии атерогенных и антиатерогенных микроРНК на фоне приёма водного экстракта дудника отражены в таблице. The obtained values of expression levels of atherogenic and antiatherogenic miRNAs against the background of taking an aqueous extract of angelica are shown in the table.
Таблица «Уровень экспрессии атерогенных микроРНК-24, -125 и антиатерогенных микроРНК-126, -222, -let7b на 1ый и 28ой день приёма per os экстракта дудника».
Table "The level of expression of atherogenic microRNA-24, -125 and anti-atherogenic microRNA-126, -222, -let7b on the 1st and 28th day of taking angelica extract per os."
Уровень экспрессии атерогенных микроРНК в плазме крови на фоне 4 недель приёма экстракта дудника в дозировке 5 капель на 10 кг веса снизился: микроРНК-24 снизилась с 12,1 до 5,4 у мужчины и с 10,4 до 7,2 у женщины; микроРНК-125 с 7,5 до 5,8 у мужчины и с 7,6 до 6,0 у женщины. Уровень экспрессии антиатерогенных микроРНК в плазме крови на фоне 4 недель приёма экстракта дудника повысился: микроРНК- 126 с 4,5 до 5,1 у мужчины и с 5,1 до 6,6 у женщины; микроРНК-222 с 3,8 до 6,7 у мужчины и с 5,8 до 7,1 у женщины и let-7b с 2,2 до 4,9 у мужчины и с 7,9 до 10,3 у женщины.
The level of expression of atherogenic miRNAs in blood plasma after 4 weeks of taking angelica extract at a dosage of 5 drops per 10 kg of body weight decreased: miRNA-24 decreased from 12.1 to 5.4 in a man and from 10.4 to 7.2 in a woman; miRNA-125 from 7.5 to 5.8 in men and from 7.6 to 6.0 in women. The level of expression of anti-atherogenic miRNAs in blood plasma after 4 weeks of taking angelica extract increased: miRNA-126 from 4.5 to 5.1 in men and from 5.1 to 6.6 in women; miRNA-222 from 3.8 to 6.7 in men and from 5.8 to 7.1 in women and let-7b from 2.2 to 4.9 in men and from 7.9 to 10.3 in women.
Claims
ФОРМУЛА ИЗОБРЕТЕНИЯ CLAIM
Способ ингибирования экспрессии атерогенных микроРНК-24, микроРНК -125 и индуцирования экспрессии антиатерогенных микроРНК- 126, микроРНК -222, микроРНК -let7b в плазме крови человека, при котором получают препарат путем сушки корней растения дудник в течение недели при температуре 24±1°С, затем измельчают высушенные корни до порошкообразного состояния, далее к 100 г измельчённого дудника добавляют 100 мл дистилированной воды, перемешивают, затем полученную смесь кипятят на водной бане в течение 1-3 часа, до уменьшения объёма жидкости в 10 раз, проводят его центрифугирование при 15000 оборотах/минуту в течение 30 минут при температуре 24±1°С, затем полученный супернатант фильтруют на фильтре Whatman №1, далее раствор концентрируют с помощью роторного испарителя Concentrator plus (Eppendorf) и насоса WP6122050 (Millipore) при следующих условиях: 1400 оборотов/мин., температура 30°С, в течении 16 часов, уровень вакуума 10 мбар, затем 5 мл полученного водного экстракта растворяют в 0,9 % водном растворе хлорида__натрия в соотношении 1:5, затем полученный препарат вводят пациенту per os в объеме 5-ти капель на каждые 10 кг его веса раз в сутки в течение 4-х недель. A method for inhibiting the expression of atherogenic microRNA-24, microRNA -125 and inducing the expression of antiatherogenic microRNA-126, microRNA -222, microRNA -let7b in human blood plasma, in which the drug is obtained by drying the roots of the angelica plant for a week at a temperature of 24±1°C , then the dried roots are crushed to a powder state, then 100 ml of distilled water are added to 100 g of crushed angelica, stirred, then the resulting mixture is boiled in a water bath for 1-3 hours, until the volume of liquid is reduced by 10 times, it is centrifuged at 15000 rpm for 30 minutes at a temperature of 24±1°C, then the resulting supernatant is filtered on a Whatman No. 1 filter, then the solution is concentrated using a Concentrator plus rotary evaporator (Eppendorf) and a WP6122050 pump (Millipore) under the following conditions: 1400 rpm/ min., temperature 30°C, for 16 hours, vacuum level 10 mbar, then 5 ml of the resulting aqueous extract is dissolved in 0.9% an aqueous solution of sodium chloride in a ratio of 1:5, then the resulting drug is administered to the patient per os in a volume of 5 drops for every 10 kg of his weight once a day for 4 weeks.
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| Application Number | Priority Date | Filing Date | Title |
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| RU2020140927A RU2752166C1 (en) | 2020-12-11 | 2020-12-11 | Method for inhibiting expression of atherogenic microrna-24, microrna-125, and inducing expression of antiatherogenic microrna-126, microrna-222, microrna-let7b in human blood plasma |
| RU2020140927 | 2020-12-11 |
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|---|---|---|---|
| PCT/RU2021/000566 WO2022124934A1 (en) | 2020-12-11 | 2021-12-10 | Inhibiting expression of atherogenic microrna-24 and microrna-125 and inducing expression of anti-atherogenic microrna-126, microrna-222 and microrna-let7b |
Country Status (2)
| Country | Link |
|---|---|
| RU (1) | RU2752166C1 (en) |
| WO (1) | WO2022124934A1 (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040223942A1 (en) * | 2003-03-06 | 2004-11-11 | Kao Corporation | Skin aging-preventing or improving agent |
-
2020
- 2020-12-11 RU RU2020140927A patent/RU2752166C1/en active
-
2021
- 2021-12-10 WO PCT/RU2021/000566 patent/WO2022124934A1/en active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040223942A1 (en) * | 2003-03-06 | 2004-11-11 | Kao Corporation | Skin aging-preventing or improving agent |
Non-Patent Citations (3)
| Title |
|---|
| BOIKO N. V ET AL.: "Rol mikroRNK v reguliatsii aktivnosti genov u eukariot", VESTNIK JUZHNOGO NAUCHNOGO TSENTRA RAN, vol. 7, no. 3, 2011, pages 69 - 78 * |
| CHENGXU MA ET AL.: "The effects of Radix Angelica Sinensis and Radix Hedysari ultrafiltration extract on X -irradiation-induced myocardial fibrosis in rats", BIOMEDICINE & PHARMACOTHERAPY, vol. 112, 2019, pages 1 - 8 * |
| DRAGANOVA A. S. ET AL.: "Ekspressia mikroRNK-27a v syvorotke krovi u patsientov s ostrym koronamym sindromom bez podema segmenta ST, perenesshikh chreskozhnoe koronamoe vmeshatelstvo", ROSSYSKY KARDIOLOGICHESKY ZHUMAL, vol. 24, no. 2, 2019, pages 70 - 75 * |
Also Published As
| Publication number | Publication date |
|---|---|
| RU2752166C1 (en) | 2021-07-23 |
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