RU2454227C1 - Composition for skeletal muscles and bone rehabilitation following orthopaedic trauma - Google Patents
Composition for skeletal muscles and bone rehabilitation following orthopaedic trauma Download PDFInfo
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- RU2454227C1 RU2454227C1 RU2011113145/15A RU2011113145A RU2454227C1 RU 2454227 C1 RU2454227 C1 RU 2454227C1 RU 2011113145/15 A RU2011113145/15 A RU 2011113145/15A RU 2011113145 A RU2011113145 A RU 2011113145A RU 2454227 C1 RU2454227 C1 RU 2454227C1
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- composition
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- orthopaedic trauma
- amino acids
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- 239000000203 mixture Substances 0.000 title claims abstract description 14
- 210000000988 bone and bone Anatomy 0.000 title claims abstract description 10
- 210000002027 skeletal muscle Anatomy 0.000 title claims abstract description 10
- 208000014674 injury Diseases 0.000 title abstract 2
- 230000008733 trauma Effects 0.000 title abstract 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims abstract description 7
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims abstract description 5
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims abstract description 5
- 229960000310 isoleucine Drugs 0.000 claims abstract description 5
- 229940024606 amino acid Drugs 0.000 claims description 9
- 235000001014 amino acid Nutrition 0.000 claims description 9
- 150000001413 amino acids Chemical class 0.000 claims description 9
- 206010061363 Skeletal injury Diseases 0.000 claims description 5
- 229960003136 leucine Drugs 0.000 claims description 4
- 229960004452 methionine Drugs 0.000 claims description 4
- FFEARJCKVFRZRR-UHFFFAOYSA-N L-Methionine Natural products CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 claims description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims description 2
- 229930064664 L-arginine Natural products 0.000 claims description 2
- 235000014852 L-arginine Nutrition 0.000 claims description 2
- 229930182844 L-isoleucine Natural products 0.000 claims description 2
- 239000004395 L-leucine Substances 0.000 claims description 2
- 235000019454 L-leucine Nutrition 0.000 claims description 2
- 229930195722 L-methionine Natural products 0.000 claims description 2
- 208000010392 Bone Fractures Diseases 0.000 abstract description 7
- 229910052500 inorganic mineral Inorganic materials 0.000 abstract description 5
- 239000011707 mineral Substances 0.000 abstract description 5
- 239000000758 substrate Substances 0.000 abstract description 4
- 239000004475 Arginine Substances 0.000 abstract description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 abstract description 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 abstract description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 abstract description 3
- 229930182817 methionine Natural products 0.000 abstract description 3
- 239000000654 additive Substances 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 150000008575 L-amino acids Chemical class 0.000 abstract 1
- 238000011084 recovery Methods 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 8
- 235000005911 diet Nutrition 0.000 description 7
- 230000037213 diet Effects 0.000 description 7
- 235000014633 carbohydrates Nutrition 0.000 description 6
- 150000001720 carbohydrates Chemical class 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- DRBBFCLWYRJSJZ-UHFFFAOYSA-N N-phosphocreatine Chemical compound OC(=O)CN(C)C(=N)NP(O)(O)=O DRBBFCLWYRJSJZ-UHFFFAOYSA-N 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 210000002303 tibia Anatomy 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 206010017076 Fracture Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 208000008425 Protein deficiency Diseases 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 235000009697 arginine Nutrition 0.000 description 2
- 229960003121 arginine Drugs 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 2
- 230000035987 intoxication Effects 0.000 description 2
- 231100000566 intoxication Toxicity 0.000 description 2
- 210000001930 leg bone Anatomy 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 235000000891 standard diet Nutrition 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 208000007788 Acute Liver Failure Diseases 0.000 description 1
- 206010000804 Acute hepatic failure Diseases 0.000 description 1
- 238000011749 CBA mouse Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 231100000836 acute liver failure Toxicity 0.000 description 1
- 230000001195 anabolic effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 150000005693 branched-chain amino acids Chemical class 0.000 description 1
- 229960003624 creatine Drugs 0.000 description 1
- 239000006046 creatine Substances 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
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Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
Изобретение относится к производству биологически активных добавок и может быть использовано в медицине при лечении переломов костей в посттравматическом периоде.The invention relates to the production of biologically active additives and can be used in medicine in the treatment of bone fractures in the post-traumatic period.
Известна способность отдельных аминокислот стимулировать анаболические процессы в скелетных мышцах (Yoshizawa F. Regulation of protein synthesis by branched-chain amino acids in vivo // Biochem. Biophys. Res. Commun. 2004. v.313. №2. P.417-422.; Kdolsky R.K., Mohr W., Savidis-Dacho H., Beer R., Puig S., Reihsner R., Tangi S., Donath K. The influence of oral L-arginine on fracture healing: an animal study // Wien Klin. Wochenschr. 2005. v.117. №19-20. P.693-701).The known ability of individual amino acids to stimulate anabolic processes in skeletal muscle (Yoshizawa F. Regulation of protein synthesis by branched-chain amino acids in vivo // Biochem. Biophys. Res. Commun. 2004. v.313. No. 2. P.417-422 .; Kdolsky RK, Mohr W., Savidis-Dacho H., Beer R., Puig S., Reihsner R., Tangi S., Donath K. The influence of oral L-arginine on fracture healing: an animal study // Wien Klin. Wochenschr. 2005. v.117. No. 19-20. P.693-701).
Однако использование этих аминокислот в составе комплексного препарата, обладающего двойным действием, одновременно направленного как на восстановление уровня энергетических субстратов в скелетных мышцах, так и на формирование полноценного костного минерала после скелетной травмы, не встречается.However, the use of these amino acids as part of a complex preparation with a double effect, simultaneously aimed both at restoring the level of energy substrates in skeletal muscles, and at forming a full-fledged bone mineral after skeletal injury, is not found.
Задачей настоящего изобретения является разработка состава композиции аминокислот для ее использования с целью восстановления уровня энергетических субстратов в скелетных мышцах и формирования полноценного костного минерала в посттравматическом периоде после скелетной травмы.The objective of the present invention is to develop the composition of the amino acid composition for its use in order to restore the level of energy substrates in skeletal muscle and the formation of a full-fledged bone mineral in the post-traumatic period after a skeletal injury.
Указанная задача достигается путем создания композиции для восстановления скелетных мышц и кости при скелетной травме, содержащей аминокислоты в равных весовых соотношениях (1:1:1:1): L-аргинин, L-метионин, L-лейцин, L-изолейцин.This task is achieved by creating a composition for the restoration of skeletal muscle and bone during skeletal injury, containing amino acids in equal weight ratios (1: 1: 1: 1): L-arginine, L-methionine, L-leucine, L-isoleucine.
Эффективность использования заявленной композиции пояснено следующими примерами.The effectiveness of the claimed composition is illustrated by the following examples.
Пример 1Example 1
Мышам-самцам линии СВА моделировали перелом костей голени. В посттравматическом периоде они были разделены на три группы. Животные первой группы (n=18) в посттравматическом периоде получали обычный сбалансированный по белку и углеводам рацион вивария. Мыши второй группы (n=18) находились на изокалорийном углеводном, обедненном белком рационе. Мыши третьей группы (n=18) после моделирования перелома костей голени также находились на изокалорийном углеводном, обедненном белком рационе, но недостаток белка у них восполняли смесью аминокислот состава лейцин, изолейцин, аргинин, метионин в весовом соотношении 1:1:1:1 в количестве, равном суммарному содержанию аминного азота в стандартном рационе. Было показано, что восполнение белка в пищевом рационе указанной смесью аминокислот предупреждало потери креатинфосфата и креатина в скелетных мышцах подопытных животных, а также способствовало более раннему формированию физиологического соотношения кальция и фосфата в костях травмированного сегмента конечности у мышей после перелома костей голени.CBA male mice were modeled for shin bone fracture. In the post-traumatic period, they were divided into three groups. Animals of the first group (n = 18) in the post-traumatic period received the usual vivarium diet balanced in protein and carbohydrates. Mice of the second group (n = 18) were on an isocaloric carbohydrate, protein-poor diet. The mice of the third group (n = 18) after modeling a shin bone fracture were also on an isocaloric carbohydrate, protein-poor diet, but the protein deficiency in them was filled with a mixture of amino acids of the composition leucine, isoleucine, arginine, methionine in a weight ratio of 1: 1: 1: 1 in amount equal to the total content of amine nitrogen in the standard diet. It was shown that the replacement of protein in the diet with this mixture of amino acids prevented the loss of creatine phosphate and creatine in the skeletal muscles of experimental animals, and also contributed to the earlier formation of the physiological ratio of calcium and phosphate in the bones of the injured limb segment in mice after fracture of the leg bones.
Пример 2Example 2
Мышам-самцам линии СВА воспроизводили острую печеночную интоксикацию четыреххлористым углеродом. Через трое суток после интоксикации у них моделировали перелом костей голени. В посттравматическом периоде все животные были разделены на три группы. Животные первой группы (n=18) в посттравматическом периоде получали обычный сбалансированный по белку и углеводам рацион вивария. Мыши второй группы (n=18) находились на изокалорийном углеводном, обедненном белком рационе. Мыши третьей группы (n=18) после моделирования перелома костей голени также находились на изокалорийном углеводном, обедненном белком рационе, но недостаток белка у них восполняли смесью аминокислот состава лейцин, изолейцин, аргинин, метионин в весовом соотношении 1:1:1:1 в количестве, равном суммарному содержанию аминного азота в стандартном рационе. Было показано, что у мышей третьей группы в посттравматическом периоде на фоне острой печеночной недостаточности отмечалось более значительное, в отличие от животных других групп, накопление креатинфосфата в скелетных мышцах травмированного сегмента. В поврежденной кости формировался полноценный костный минерал, в котором соотношение между кальцием и фосфатом соответствовало физиологической норме, характерной для интактных мышей линии СВА.The CBA male mice reproduced acute hepatic intoxication with carbon tetrachloride. Three days after intoxication, they modeled a fracture of the leg bones. In the post-traumatic period, all animals were divided into three groups. Animals of the first group (n = 18) in the post-traumatic period received the usual balanced protein and carbohydrate diet of the vivarium. Mice of the second group (n = 18) were on an isocaloric carbohydrate, protein-poor diet. The mice of the third group (n = 18) after modeling a shin bone fracture were also on an isocaloric carbohydrate, protein-depleted diet, but their protein deficiency was compensated by a mixture of amino acids of the composition leucine, isoleucine, arginine, methionine in a weight ratio of 1: 1: 1: 1 in amount equal to the total content of amine nitrogen in the standard diet. It was shown that in mice of the third group in the post-traumatic period against the background of acute liver failure, there was a more significant, in contrast to animals of other groups, accumulation of creatine phosphate in the skeletal muscle of the injured segment. A full-fledged bone mineral was formed in the damaged bone, in which the ratio between calcium and phosphate corresponded to the physiological norm characteristic of intact CBA mice.
Применение предложенной композиции показало, что данный состав аминокислот восстанавливает уровень энергетических субстратов в скелетных мышцах и формирует полноценный костный минерал в посттравматическом периоде после скелетной травмы.The use of the proposed composition showed that this amino acid composition restores the level of energy substrates in skeletal muscle and forms a full-fledged bone mineral in the post-traumatic period after a skeletal injury.
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| Application Number | Priority Date | Filing Date | Title |
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| RU2011113145/15A RU2454227C1 (en) | 2011-04-05 | 2011-04-05 | Composition for skeletal muscles and bone rehabilitation following orthopaedic trauma |
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| RU2011113145/15A RU2454227C1 (en) | 2011-04-05 | 2011-04-05 | Composition for skeletal muscles and bone rehabilitation following orthopaedic trauma |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2005111973A (en) * | 2002-09-20 | 2006-03-10 | Новартис АГ (CH) | LEICIN-ENRICHED NUTRIENT COMPOSITIONS |
| WO2006105112A2 (en) * | 2005-03-29 | 2006-10-05 | Ajinomoto Co., Inc. | Amino acid-containing composition for preventing or remedying in the skeletal muscle of aged people |
| RU2383209C2 (en) * | 2005-10-26 | 2010-03-10 | Хилл'С Пет Ньютришн, Инк. | Composition and methods for increase of nonfat muscle bulk and/or reduction of fat growth |
| RU2414897C2 (en) * | 2005-11-30 | 2011-03-27 | Нестек С.А. | Methods of treating muscular mass loss |
-
2011
- 2011-04-05 RU RU2011113145/15A patent/RU2454227C1/en not_active IP Right Cessation
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2005111973A (en) * | 2002-09-20 | 2006-03-10 | Новартис АГ (CH) | LEICIN-ENRICHED NUTRIENT COMPOSITIONS |
| WO2006105112A2 (en) * | 2005-03-29 | 2006-10-05 | Ajinomoto Co., Inc. | Amino acid-containing composition for preventing or remedying in the skeletal muscle of aged people |
| RU2383209C2 (en) * | 2005-10-26 | 2010-03-10 | Хилл'С Пет Ньютришн, Инк. | Composition and methods for increase of nonfat muscle bulk and/or reduction of fat growth |
| RU2414897C2 (en) * | 2005-11-30 | 2011-03-27 | Нестек С.А. | Methods of treating muscular mass loss |
Non-Patent Citations (1)
| Title |
|---|
| Yoshizawa F. Regulation of protein synthesis by branched-chain amino acids in vivo // Biochem. Biophys. Res. Commun. - 2004. v.313. N.2 p.417-422. * |
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