WO2022203545A1 - Utilisation d'une émulsion phospholipidique pour traiter le syndrome d'ischémie-reperfusion - Google Patents
Utilisation d'une émulsion phospholipidique pour traiter le syndrome d'ischémie-reperfusion Download PDFInfo
- Publication number
- WO2022203545A1 WO2022203545A1 PCT/RU2022/000084 RU2022000084W WO2022203545A1 WO 2022203545 A1 WO2022203545 A1 WO 2022203545A1 RU 2022000084 W RU2022000084 W RU 2022000084W WO 2022203545 A1 WO2022203545 A1 WO 2022203545A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- emulsion
- reperfusion
- ischaemia
- reperfusion syndrome
- syndrome
- Prior art date
Links
- 239000000839 emulsion Substances 0.000 title claims abstract description 27
- 208000028867 ischemia Diseases 0.000 title claims abstract description 21
- 208000011580 syndromic disease Diseases 0.000 title claims abstract description 16
- 150000003904 phospholipids Chemical class 0.000 title claims abstract description 12
- 210000000056 organ Anatomy 0.000 claims abstract description 9
- 230000010410 reperfusion Effects 0.000 claims abstract description 9
- 239000000203 mixture Substances 0.000 claims abstract description 7
- 208000010125 myocardial infarction Diseases 0.000 claims abstract description 7
- CXQWRCVTCMQVQX-LSDHHAIUSA-N (+)-taxifolin Chemical compound C1([C@@H]2[C@H](C(C3=C(O)C=C(O)C=C3O2)=O)O)=CC=C(O)C(O)=C1 CXQWRCVTCMQVQX-LSDHHAIUSA-N 0.000 claims abstract description 6
- XCGZWJIXHMSSQC-UHFFFAOYSA-N dihydroquercetin Natural products OC1=CC2OC(=C(O)C(=O)C2C(O)=C1)c1ccc(O)c(O)c1 XCGZWJIXHMSSQC-UHFFFAOYSA-N 0.000 claims abstract description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000001990 intravenous administration Methods 0.000 claims abstract description 4
- 239000008344 egg yolk phospholipid Substances 0.000 claims abstract description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 3
- 230000007654 ischemic lesion Effects 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 239000004471 Glycine Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000002562 thickening agent Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 12
- 229940079593 drug Drugs 0.000 abstract description 9
- 206010063837 Reperfusion injury Diseases 0.000 abstract description 6
- 230000000302 ischemic effect Effects 0.000 abstract description 5
- 210000000170 cell membrane Anatomy 0.000 abstract description 3
- 230000036542 oxidative stress Effects 0.000 abstract description 3
- 230000002401 inhibitory effect Effects 0.000 abstract 2
- 206010061225 Limb injury Diseases 0.000 abstract 1
- 238000002648 combination therapy Methods 0.000 abstract 1
- 229940124446 critical care medicine Drugs 0.000 abstract 1
- 229940124645 emergency medicine Drugs 0.000 abstract 1
- 208000037906 ischaemic injury Diseases 0.000 abstract 1
- 238000001356 surgical procedure Methods 0.000 abstract 1
- 229940124597 therapeutic agent Drugs 0.000 abstract 1
- 206010061216 Infarction Diseases 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 230000007574 infarction Effects 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 230000037396 body weight Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- 241000700159 Rattus Species 0.000 description 3
- 210000002216 heart Anatomy 0.000 description 3
- 231100000518 lethal Toxicity 0.000 description 3
- 230000001665 lethal effect Effects 0.000 description 3
- 230000003680 myocardial damage Effects 0.000 description 3
- 208000007201 Myocardial reperfusion injury Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 206010000891 acute myocardial infarction Diseases 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 210000003414 extremity Anatomy 0.000 description 2
- 230000002107 myocardial effect Effects 0.000 description 2
- 208000031225 myocardial ischemia Diseases 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 230000002537 thrombolytic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- PKDBCJSWQUOKDO-UHFFFAOYSA-M 2,3,5-triphenyltetrazolium chloride Chemical compound [Cl-].C1=CC=CC=C1C(N=[N+]1C=2C=CC=CC=2)=NN1C1=CC=CC=C1 PKDBCJSWQUOKDO-UHFFFAOYSA-M 0.000 description 1
- 206010002388 Angina unstable Diseases 0.000 description 1
- 208000001778 Coronary Occlusion Diseases 0.000 description 1
- 206010011086 Coronary artery occlusion Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000034486 Multi-organ failure Diseases 0.000 description 1
- 208000010718 Multiple Organ Failure Diseases 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 102000003840 Opioid Receptors Human genes 0.000 description 1
- 108090000137 Opioid Receptors Proteins 0.000 description 1
- 208000007814 Unstable Angina Diseases 0.000 description 1
- 206010047281 Ventricular arrhythmia Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 230000005961 cardioprotection Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 230000000254 damaging effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 150000002642 lithium compounds Chemical class 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000009979 protective mechanism Effects 0.000 description 1
- 229960000424 rasburicase Drugs 0.000 description 1
- 108010084837 rasburicase Proteins 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
-
- 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
- A61K36/13—Coniferophyta (gymnosperms)
- A61K36/15—Pinaceae (Pine family), e.g. pine or cedar
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Definitions
- Ischemia-reperfusion syndrome is a complex of clinical manifestations associated with damage to cells, tissues and organs as a result of ischemia and subsequent restoration of blood circulation, accompanied by multiple organ failure.
- One of the most urgent tasks is the problem of relief of ischemia-reperfusion syndrome in myocardial infarction.
- Reperfusion-induced death of cardiomyocytes that should have remained viable after the onset of an ischemic event is defined as lethal myocardial reperfusion injury.
- Lethal myocardial reperfusion injury negates the benefits of myocardial reperfusion (in terms of reducing MI size) and thus represents an important target for cardioprotection in patients. There is currently no effective therapy to reduce lethal injury.
- rasburicase (patent RU 2482187) for the prevention and treatment of complications caused by ischemia and reperfusion in the heart.
- Lipin is prescribed in the treatment of acute myocardial infarction and unstable angina.
- Lipin is prescribed at a dose of 35 mg/kg of body weight 4 times a day.
- the drug is administered intravenously slowly.
- the course of treatment is 4-5 days.
- Lipin is prescribed at a dose of 30 mg/kg of body weight 30 minutes before the administration of a thrombolytic, and then at 15 mg/kg of body weight 4 times a day.
- the disadvantage of this drug is the limited possibility of clinical use, especially in emergency cases.
- the conditions for storage and preparation of the composition are significantly limited: store in a freezer at a temperature of -20 to -10 °C. Store the finished emulsion at a temperature of 2-6 ° C for no more than 6 hours. Liposomal emulsion is prepared immediately before use. Before preparing the vial with the drug should be kept at room temperature for about 30 minutes.
- the invention is aimed at treating ischemic lesions of various tissues (acute myocardial infarction, acute cerebrovascular accident, chronic/acute ischemia of the lower extremities).
- the problem that this invention solves is to limit the size of the ischemic lesion, in particular the consequences of the ischemia-reperfusion syndrome.
- the technical result is a reduction in the area of ischemic damage with the introduction of the emulsion.
- the result is achieved by stopping oxidative stress caused by ischemia-reperfusion syndrome, as well as by restoring cell membranes.
- the problem is solved by using a phospholipid emulsion containing an effective amount of dihydroquercetin for the treatment of ischemia-reperfusion syndrome in patients with ischemic lesions of organs and limbs, where the phospholipid emulsion has the following composition in g per 100 ml: glycine 3.5 ⁇ 0.5 egg lecithin 3.5 ⁇ 0.8 dihydroquercetin 0.35 ⁇ 0.1 water - the rest.
- the use of the emulsion involves the intravenous administration of the emulsion.
- Ischemic damage to organs and limbs can be, in particular, a heart attack or stroke.
- the specified phospholipid emulsion is used as part of complex therapy.
- Said phospholipid emulsion may additionally contain thickeners and/or pharmaceutically acceptable excipients.
- Phospholipid emulsion is administered intravenously 2 minutes before reperfusion in doses of 0.29 - 5.7 ml/kg of body weight for mammals.
- Emulsion significantly reduces the damage to cells, tissues and organs in ischemia-reperfusion syndrome
- the claimed result was demonstrated in an experiment on modeling myocardial ischemia-reperfusion, followed by reperfusion injury, as close as possible to the real clinical picture.
- the emulsion introduced in volumes of 1.45 ml/kg (F-0.5) and 2.9 ml/kg (F-1) reduced the size of myocardial lesion by 1.85 and 2.83 times, respectively, compared with the control group C-0.5.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Cardiology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Dispersion Chemistry (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Alternative & Traditional Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
L'invention se rapporte au domaine de la médecine, notamment à des moyens d'action thérapeutique, et a pour but de supprimer les dommages de reperfusion d'organes en cas de syndrome d'ischémie-reperfusion. L'invention peut être utilisée en chirurgie, en cardiologie, en réanimation, en médecine d'urgence, en réhabilitation, y compris pour un infarctus du myocarde (IM), ainsi qu'en pharmacologie afin de créer de nouvelles compositions médicamenteuses afin de traiter des patients présentant un syndrome d'ischémie-reperfusion. A cette fin, l'invention concerne l'utilisation d'une émulsion phospholipidique comprenant une quantité efficace de dihydroquercétine chez des patients soufrant d'une affection ischémique des organes et des extrémités, laquelle émulsion phospholipidique possède la composition suivante en g. pour 100 ml: glycine 3,5±0,5; lécithine d'oeuf 3,5±0,8; dihydroquercétine 0,35±0,1; le reste se composant d'eau. L'utilisation comprend l'administration intraveineuse et/ou par voie orale de l'émulsion dans le cadre d'une thérapie complexe. L'administration intraveineuse de l'émulsion se fait 2 minutes avant la reperfusion dans des doses de 0,29-5,7 ml/kg. Le résultat technique consiste en une diminution de la zone d'affection ischémique lors de l'administration de l'émulsion. Ce résultat est atteint par la suppression du stress oxydant induit par le syndrome d'ischémie-reperfusion, et par le rétablissement des membranes cellulaires.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| RU2021107716 | 2021-03-24 | ||
| RU2021107716A RU2766681C1 (ru) | 2021-03-24 | 2021-03-24 | Применение фосфолипидной эмульсии, содержащей эффективное количество дигидрокверцетина, для лечения синдрома ишемии-реперфузии у пациентов с ишемическими поражениями органов и конечностей |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2022203545A1 true WO2022203545A1 (fr) | 2022-09-29 |
Family
ID=80736690
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/RU2022/000084 WO2022203545A1 (fr) | 2021-03-24 | 2022-03-22 | Utilisation d'une émulsion phospholipidique pour traiter le syndrome d'ischémie-reperfusion |
Country Status (2)
| Country | Link |
|---|---|
| RU (1) | RU2766681C1 (fr) |
| WO (1) | WO2022203545A1 (fr) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2622024C2 (ru) * | 2015-12-01 | 2017-06-08 | Общество с ограниченной ответственностью "Флавимакс" | Применение липосомальной эмульсии с дигидрокверцетином "фламена" для лечения хронических эндометритов с аутоиммунными нарушениями при бесплодии |
-
2021
- 2021-03-24 RU RU2021107716A patent/RU2766681C1/ru active
-
2022
- 2022-03-22 WO PCT/RU2022/000084 patent/WO2022203545A1/fr active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2622024C2 (ru) * | 2015-12-01 | 2017-06-08 | Общество с ограниченной ответственностью "Флавимакс" | Применение липосомальной эмульсии с дигидрокверцетином "фламена" для лечения хронических эндометритов с аутоиммунными нарушениями при бесплодии |
Non-Patent Citations (4)
| Title |
|---|
| MAKSIMOVICH N.E. ET AL.: "Korrigiruiushchie effekty digidrokvertsetina pri ishemii-reperfuzii golovnogo mozga", BIOMEDITSINSKAIA KHIMIIA, vol. 60, no. 6, 2014, pages 643 - 650 * |
| SHU ZUNPENG ET AL.: "Cardioprotective effects of dihydroquercetin against ischemia reperfusion injury by inhibiting oxidative stress and endoplasmic reticulum stress-induced apoptosis via the PDK/Akt pathway", FOOD FUNCT., vol. 10, no. 1, 2019, pages 203 - 215, XP055974467 * |
| SUNIL CHRISTUDAS ET AL.: "An insight into the health-promoting effects of taxifolin (dihydroquercetin", PHYTOCHEMISTRY, vol. 166, 2019, XP085782412, DOI: doi.org/10.1016/j. phytochem. 2019.112066 * |
| WANG YEA-HWEY ET AL.: "Taxifolin ameliorates cerebral ischemia-reperfusion injury in rats through its anti -oxidative effect and modulation of NF-kappa V activation", JOURNAL OF BIOMEDICAL SCIENCE, 2006, pages 127 - 141, XP019272247, DOI: 10.1007/sl 1373-005-9031-0 * |
Also Published As
| Publication number | Publication date |
|---|---|
| RU2766681C1 (ru) | 2022-03-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Beck et al. | Scientific basis for the surgical treatment of coronary artery disease | |
| KR100343314B1 (ko) | 만성통증치료에유용한레보부피바카인 | |
| US11298403B2 (en) | Therapeutic agent for inflammatory bowel disease | |
| WO2001015717A1 (fr) | Agents contenant du ginseng destines a proteger les cellules cerebrales ou les cellules nerveuses | |
| KR20010101218A (ko) | 진세노사이드 Ｒｂ₁을 함유하는 뇌세포 또는 신경세포보호제 | |
| KR100696417B1 (ko) | 진세노사이드 Ｒｂ₁을 함유하는 뇌혈관 재생ㆍ재구축 촉진제 및 신경조직 이차변성 억제제 | |
| JPH05501856A (ja) | 脳及び筋肉組織傷害による浮腫の治療剤 | |
| RU2712448C1 (ru) | Способ кардиопротекции ишемических и реперфузионных повреждений в остром периоде инфаркта миокарда | |
| RU2766681C1 (ru) | Применение фосфолипидной эмульсии, содержащей эффективное количество дигидрокверцетина, для лечения синдрома ишемии-реперфузии у пациентов с ишемическими поражениями органов и конечностей | |
| Tarasova et al. | Effect of pharmacological preconditioning with incretinomimetics exenatide and vildagliptin on the survival of ischemic tissues | |
| MX2014003256A (es) | Uso de hidroxamatos de indolilo e indolinilo para tratar insuficiencia cardiaca o lesion neuronal. | |
| CN1954812B (zh) | 依达拉奉的新用途 | |
| CA2304956C (fr) | Agents preventifs ou remedes pour les maladies ischemiques | |
| EP2559432B1 (fr) | Moyen pour la prévention et le traitement de pancréatite aiguë et chronique | |
| EP0305181A2 (fr) | Ethyl-(+)-apovincaminat pour le traitement des symptômes cliniques de la démyélinisation d'origine autoimmune | |
| NL2025156B1 (en) | Use of prostaglandin e1 in preparation of medicament for treating intracerebral hemorrhage | |
| CN106421746A (zh) | [Pyr1]‑Apelin‑13 作为长效酰胺类局麻药中毒所致心脏停搏的抢救药物的应用 | |
| EP1795193B1 (fr) | Histidine pour supprimer la necrose des tissus cerebraux attribues a une ischemie de longue duree | |
| Fayed et al. | Comparative study between effects of addition of fentanyl versus dexmedetomidine to local anesthetic mixture for peribulbar block for cataract surgery | |
| Trofimova et al. | Medicinal Peptide Drugs: A Promising Direction in Modern Pharmacology | |
| CN113150067B (zh) | Gsdme抑制剂及其在肿瘤化疗诱导的消化道损伤防治中的用途 | |
| US20210161993A1 (en) | Method for accelerated healing of burn wounds | |
| CN108853483B (zh) | 经修饰的胸腺素β4在治疗脑缺血再灌注损伤方面的用途 | |
| Gao et al. | The protective effect of a short peptide derived from cold-inducible RNA-binding protein in a rat model of cardiac arrest and resuscitation | |
| US20080039500A1 (en) | Cerebral Infarction Suppressant |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 22776211 Country of ref document: EP Kind code of ref document: A1 |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 22776211 Country of ref document: EP Kind code of ref document: A1 |