Описание
Препарат Вимизим положительно действует при таком заболевании как мукополисахаридоз IV типа А, его виляние выражается в улучшении физической активности у пациентов с данным заболеванием. Действующее вещество — Элосульфаза альфа – это рекомбинантная форма человеческой N-ацетилгалактозамин-6-сульфатазы (rhGALNS), получаемая из клеток яичников китайского хомячка с помощью рекомбинантной ДНК-технологии.
Элосульфаза альфа обеспечивает экзогенным ферментом rhGALNS, который проникая внутрь клетки, убыстряет катаболизм хондроитин-6-сульфата (Х6С), гликозаминогликанов (ГАГ), кератансульфата (КС). Препарат Вимизайм поступает в лизосомы клеток и при помощи катион-независимых маннозо-6-фосфатных рецепторов, восстанавливает активность ферментов GALNS и клиренс кератансульфата у лиц с синдромом Моркио типа А — мукополисахаридозом IV типа А (МПС IVa). Недостаточная деятельность фермента сульфатазы ведет к накоплению субстратов хондроитин-6-сульфата, гликозаминогликанов, кератансульфата в лизосомах клеток всего организма, что вызывает нарушения функций клеток, тканей и органов.
Положительное влияние элосульфазы альфа при мукополисахаридозе IV типа А выражается в улучшении физической выносливости (измеряется тестом 6-минутной ходьбы), и при этом понижением значений кератансульфата в моче, что свидетельсвует о положительном фармакодинамическом эффекте препарата Вимизайм на патологическое накопление кератансульфата в лизосомах клетки.
Состав Вимизим
Один флакон содержит 5 мл концентрата:
- Действующее вещество: элосульфаза альфа – 5 мг
- Дополнительные вещества: натрия ацетата тригидрат, L- аргинина гидрохлорид, полисорбат 20, натрия дигидрофосфата дигидрат, D- сорбит, вода для инъекций.
Показания к применению Вимизим
- Лечение у пациентов всех возрастов мукополисахаридоза IV тип А — синдром Моркио тип А.
Фармакодинамика
В проведенных клинических исследованиях с применением Вимизим оценивалось влияние лечения на системные проявления мукополисахаридоза IVA типа А (МПС IVA) по разным показателям, включая дыхательную функцию, выносливость, подвижность и скорость роста, а также содержание КС в моче.
Всего в шести клинических исследованиях участвовали и принимали Вимизим 235 пациентов с мукополисахаридозом IV A типа (МПС IVA).
Безопасность и эффективность Вимизим оценивали в рандомизированном, двойном слепом, плацебо-контролируемом клиническом исследовании с участием 176 лиц с мукополисахаридозом IV типа A (в возрасте от 5 до 57 лет). У большинства больных отмечалась пониженная выносливость, низкий рост и нарушения со стороны опорно-двигательного аппарата. Для участия в эксперименте отбирали больных, которые на начальном уровне могли пройти более 30 метров, но менее чем 325 метров в 6-минутном тесте ходьбы.
Пациенты получали элосульфазу альфа по 2 мг / кг еженедельно или 2 мг/кг каждые две недели или плацебо в среднем за 22 недели. Перед каждой системой все пациенты принимали антигистаминные препараты. Первичнoй конечной точкой было изменение относительнo исходного уровня расстоянии в 6-минутном тесте ходьбы по сравнению с плацебо на 22-й неделе.
Смоделирован эффект лечения относительно расстояния, пройденного за 6 минут, по сравнению с плацебо, составлял 22,5 м (ДИ 95, 4,0, 40,9; p = 0,0174) для больных, получавших лечение по схеме 2 мг/кг в неделю. Различие было наибольшим между группами плацебо и еженедельного введения препарата относительно конечной точки. Рeзультаты в группе лечения с введением исследуемогo препарата каждые двe недели на расстояние, пройденного за 6 минут были сопоставимы с результатами в группе плацебо.
В дополнительных продолжениях исследований у пациентов, получавших элосульфазу альфа в дозе 2 мг / кг еженедельно, отмечалось сохранение первоначального улучшения относительно выносливости в течение периода до 156 недель.
Дети
Важно начать лечение как можно раньше. Большинство пациентов, принимавших Вимизим в ходе клинических исследований, принадлежали к возрастному диапазону от 5 до 17 лет.
Фармакокинетика
Фармакокинетические параметры препарата Вимизим исследовались на группе из 23 лиц с МПС IVA, которые еженедельно в течении 22 недель получали внутривенные системы в течение 4-х часов с веществом Элосульфаза альфа в составе в дозировке 2 мг/кг. В дальнейшем сравнивали фармакокинетические показатели на 0 неделе и на 22 неделе терапии.
Среднее значение максимальной концентрации препарата в плазме крови (Сmax) и плoщади под кривой «кoнцентрация-время» на 22-й неделе увеличились в сравнении с неделей 0 на 192% и 181%, соответственно. Период полувыведения препарата (Т1/2) вырос с 7,52 минут до 35,9 минут. Клиренс элосульфазы альфа у женщин и мужчин был сопоставимым; не наблюдалось влияние возраста или массы тела на клиренс на 22-ой неделе лечения препаратом.
Оценивалось влияние антител на фармакокинетику к элосульфазе альфа. Очевидной зависимости между общим титром антител и клиренсом элосульфазы альфа не было обнаружено. Однако, у лиц с наличием нейтрализующих антител значение общего клиренса (CL) были ниже, а периода полувыведения (Т1/2) — длиннее.
Наличие изменений в фармакокинетическом профиле, присутствие нейтрализующих антител не влияло на фармакодинамику препарата, его эффективность и безопасность использования. Не наблюдалось кумуляции элосульфазы альфа в плазме крови после еженедельного введения.
Элосульфаза альфа — это белок, который, возможно метаболически распадается путем гидролиза пептидов. Нарушение функции печени не влияет на фармакокинетику элосульфазы альфа. Элиминация элосульфазы альфа почками считается незначительным.
Результаты доклинических исследований безопасности
По данным доклинических исследований, по фармакологической безопасности, которые оценивали влияние препарата на центральную нервную, сердечно-сосудистую и дыхательную системы, токсичность при однократном и многократном введении препарата у обезьян и крыс, фертильность и эмбриофетальное развитие у кроликов и крыс, применение элосульфазы альфа у человека не представляло какой-либо опасности. Исследования перинатального и постнатального развития у крыс не выявили негативного влияния на пре- и постнатальное развитие плода при введении препарата в дозах до 20 мг/кг.
На животных не проводились долгосрочные исследования с целью оценки возможного канцерогенного или мутагенного действия элосульфазы альфа.
Эксперименты репродуктивной токсичности на крысах при введении дозировки в 10 раз превышающих дозу у человека, не показали отрицательного влияния на фертильность или репродуктивную способность.
Иммуногенность Вимизим
При использовании препарата Вимизим, также как при использовании других лекарственных препаратов белковой природы, возможно развитие иммунных реакций. На количество частоты образования антител в значительной степени оказывают влияние различные факторы: специфичность и чувствительность используемых лабораторных тестов; особенность методологии выполнения анализа, время сбора образцов, способов обработки образцов, основное заболевание и прием сопутствующих препаратов. Поэтому сравнение частоты образования антител к препарату Вимизайм с частотой образования антител к другим препаратам может быть не достоверным.
У всех больных, получавших лечение препаратом Вимизим, выявлялось образование антител к препарату. Минимум 1 раз в течение исследования выявлялись нейтрализующие антитела, блокирующие связывание препарата с катион-независимым маннозо-6-фосфатным рецептором. В течении исследования у пациентов наблюдались симптомы повышение эффективности лечения и постепенного снижения концентрации кератансульфата в моче, в независимости от наличия антител к препарату. Не наблюдалась связь между высоким титром антител или наличием нейтрализующих антител и уменьшением эффективности или появлением прочих реакций гиперчувствительности.
Антитела класса IgE к элосульфазе альфа обнаруживались у ≤10% пациентов и не всегда сопровождались появлением анафилаксии или других реакций гиперчувствительности и/или отказом от лечения.
Особые указания препарата Вимизим
В случаях тяжелых форм заболеваний очень важно начать лечение как можно раньше, до выявления необратимых проявлений. Однако, как и в случае внутривенного применения других лекарственных препаратов белковой природы, возможно развитие тяжелых реакций гинерчувствительности. Необходимо учитывать риски и преимущества при проведении лечения препаратом Вимизим. Компрессия спинного мoзга или шейного отдела спинного мoзга (КСМ) — это тяжелое осложнение и может развиваться при не леченном течении заболевания. В период проведения лечения нужно контролировать состояние больных на предмет выявления признаков и симптомов Компрессии спинного мoзга (боль в спине, паралич конечностей ниже уровня компрессии, недержание мочи и кала) и обеспечить им необходимый медицинский уход.
Фармацевтические характеристики
Прозрачный или слегка опалесцирующий раствор, бесцветного или светло-желтого цвета, без посторонних механических включений.
Упаковка, срок годности, условия хранения
Концентрат для приготовления раствора для инфузий, 1 мг/мл. По 5,0 мл во флаконе из бесцветного боросиликатного стекла, герметично закупоренный бутиловой резиновой пробкой и обжатый алюминиевым колпачком с отщёлкивающейся крышкой.
По одному флакону вместе с инструкцией по применению упаковано в пачке из картона.
Хранить в недоступном для детей месте. Хранить в оригинальной упаковке в холодильнике при температуре от +2 до +8 °С. Не замораживать и не встряхивать. Хранить в защищенном от света месте.
Срок годности 3 года. Не применять после истечения срока годности, указанного на упаковке.
Наша компания работает как на территории Казахстана, так и осуществляет доставку в страны ближнего зарубежья. Обращайтесь к нам за консультациями по контактным телефонам.
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Позвоните и узнайте цену Вимизим (Элосульфаза альфа)
Работаем и отправляем Вимизим (Элосульфаза альфа) по странам СНГ: Россия, Украина, Кыргызстан (Бишкек), Белоруссия, Узбекистан (Ташкент),
а также можем отправить Вимизим (Элосульфаза альфа) по регионам Казахстана: Нур-Султан (Астана), Шымкент, Талдыкорган, Актау и другие.
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You also can click on the hyperlink to see the assorted bicep exercises for girls that our team of specialists created
with females in mind, as well as the other follow-along routines listed below.
1️⃣ Rigidity in the Stretched Position – Exercises that place excessive mechanical rigidity on the biceps when totally stretched rank
greater, as research suggests this leads to higher muscle development.
Pushups might help construct biceps, however not as nicely as workouts
like the Barbell Cheat Curl and Dumbbell Curls which particularly
goal the biceps. The first place is the Supinated Cross Body Curl which allows us to
preferentially hit the long head of the biceps.
Maintain the contraction on the prime for a exhausting one
depend, then slowly lower the bar alongside the same path.
Stand in entrance of a low-pulley cable with a short straight bar hooked up.
Adjust a preacher bench in order that the highest of
the pad matches securely beneath your armpits.
Take an inside-shoulder-width, underhand grip on the EZ-curl bar—so your palms are angled inward— and place your higher
arms parallel to one another on the pad. This workout is for you
should you practice at home (or simply love dumbbells).
It’s a whole dumbbell arm exercise for constructing your biceps
and triceps within the comfort of your house.
This is perfect for these new to biceps coaching or if you prefer a lower-volume
approach. This variation earns an S-tier rating as probably the greatest bicep exercises for constructing the biceps peak
and targeting the lengthy head. I place 21s within the B-tier
as they’re a enjoyable approach to increase quantity and challenge your biceps, however they don’t supply the same effectiveness as different bicep workouts for hypertrophy.
Whereas the standing dumbbell curl is not the absolute best for
isolating the biceps, its versatility earns it a spot within the A-tier.
You can easily add variations to focus on both heads of the biceps, making
it a useful gizmo in your routine. The combined grip curl combines an overhand and underhand
grip, with one hand supinated and the opposite pronated, making a problem for each the forearm flexors and extensors.
This limits its effectiveness considerably in totally growing the biceps, notably in the elongated range of motion, but it remains a staple for building mass and foundational power.
They are usually carried out after the barbell
curl; however, you’ll be able to carry out them at any level all through your workout.
You should perform the barbell biceps curl firstly of your arm training routine.
However, should you practice your back and biceps on the
same day, you need to do it after you complete your back
routine. You might know some of them, however some of these exercises are distinctive.
This is probably the most common chest movement, however
once once more it’s essential to use proper form on this lift to keep away from the
chance of harm. You can use these exercises to craft your individual custom routine,
or you probably can observe considered one of our pre-made
bicep exercises for novices when you just need to get on with coaching.
Adding curl bars to your train regimen can help construct greater and stronger biceps and
triceps. Their distinctive form can also assist you to achieve greater ROM on exercises like bent-over rows and ground presses.
Doing so shifts a few of the work from your biceps to the front
of your shoulders. If you needed to pick only one train in your biceps, the dumbbell curl would be a great selection. It is usually at
or near the highest of the record of biceps train decisions for novices and advanced trainees alike.
Entrance and heart on the upper arm, your biceps
are one of the visible muscle tissue and infrequently the primary ones folks discover.
When someone flexes – you guessed it – it’s usually the biceps they’re showing off.
You also can attempt ending your again exercise with the below exercises.
If your health club has Hammer Energy tools, I extremely encourage you to attempt your
7 units on these. As A Result Of of the depth of this program, you prepare every muscle solely once a week.
FST-7 creator Hany Rambod takes Jeremy Buendia through an intense shoulder and triceps exercise within the video beneath.
This will give you a good idea of what to anticipate from the program you’ll
be starting. You can also study extra about FST-7 on Hany
Rambod’s web site right here.
If you had been to train biceps each single day, the muscle group would get overworked,
and you’ll likely expertise muscular fatigue, which could hinder performance during periods.
Lastly, you’ll finish this whole bicep exercise routine with the formidable drag curl.
Because let’s be honest, even if you’re coaching for biceps energy, you still need to
get a good pump within the course of. Additionally, don’t get
tempted to throw in extra sets or further workout routines.
When you’re a novice, you also can make significant positive aspects from a ridiculously low quantity of coaching quantity.
Carry Out the supersets back-to-back after which relaxation 2
minutes between pairings. So you’d do exercise A immediately adopted by train B, adopted by 2 minutes of rest.
If you begin dishonest by swinging the bar up, you haven’t actually
gotten stronger in your biceps and brachialis.
As A End Result Of of how your biceps brachii inserts in your radius in your
forearm, it is also a strong supinator. Biceps brachii is at its strongest when your forearm is supinated,
and at its weakest when your forearm is pronated (palm turned down).
Take a 2–3 minute breather, then end your workout in style with the incline dumbbell curl.
In this workout, you’ll be coaching chest first, then move
on to biceps. Feel free to flip things around and start with
biceps should you like, but coaching chest earlier than biceps most likely feels
extra pure for most individuals. Manish is a NASM-certified health
and vitamin coach with over 10 years of experience in weight lifting and fats loss health coaching.
The deadstop seated barbell curl is all about concentric contraction. Starting every rep from a complete cease with the bar resting on your thighs eliminates momentum and requires your biceps to
do more work. Performing it seated removes lower-body involvement, preserving the strain in your biceps and isolating them for an enhanced muscle pump.
As we often do in our workouts, we’ll begin this routine off with a compound exercise.
Because the biceps are connected to a hinge joint, there
is some limitation on which exercises we are able to do in our training session. Biceps workouts have different power curves, that means that they’ll create a stronger contraction both in the either to begin with,
center, or end of the biceps’ ranges of motion. As usual, I’ll be breaking out the Muscle Markers to show you the
different muscles the biceps are comprised of,
and then we’ll check out the forms of movements they are liable for.
The cause I selected EZ Bar curls with a reverse grip is because, as demonstrated on this 2015 study by Staudenmann et al., the brachialis inserts onto the ulna
somewhat than the radius.
Whereas the rep scheme given (3X8-12) is sweet for the other curls, you will carry out cheat curls using a 3X5
rep scheme and a 3-5 second eccentric. Comparable to the above, you want to also use totally different
hundreds together with your coaching. This is greatest
carried out with the compound movements, BUT
you can also use lighter hundreds with the compound movements as properly.
If you’re pondering this is comparable advice to every other muscle, you’d be
correct.
Really Feel free to take the biceps exercises and do them as a stand-alone exercise or with, for
instance, a back workout. In common dumbbell curls, you raise both
dumbbells concurrently, but with alternating dumbbell curls,
you lift one dumbbell at a time, alternating between your left and right.
Doing so enables you to focus more on each arm individually and might help you pay more consideration to good type.
Neither model is superior to the opposite, so decide the one you want one of the best.
The brachialis and brachioradialis won’t get the glory just like the biceps.
Nonetheless, they play an necessary position in making sure you presumably can raise, carry, wave, and
perform many other on a regular basis tasks together with your arms.
The cable arm curl is considered one of the most highly beneficial bicep workout routines for novices as a end result of it produces extra joint-friendly resistance than comparable free weight lifts.
Since the cable machine stabilizes the load for you, to an extent, you’ll find a
way to focus extra consideration on blasting
your biceps and making them grow. Free weights certainly have their place, however they also
carry a better damage risk than cables—especially for beginners.
With the bar biceps curl, assume inverted row however you’re using your biceps and not your again. The motion is
all within the elbows, and since you arms a little extensive, it is good for targeting the brief head of the biceps for some arm thickness.
This variation requires much less weight than a regular curl
but doubles the reps to train either side evenly.
It enhances grip power, addresses forearm strength imbalances, and builds forearm and grip power.
Keep your wrists neutral to avoid pointless pressure, and regulate your grip width for
consolation.
Prepare your back and biceps once a week should you work out three to four
days every week and twice should you work out six days every week.
You also can do an alternate curl in the method in which to target one arm at a time.
Good news, irrespective of what quantity of candles
are on the birthday cake, there isn’t any cap on how
much your weapons can develop.
Supersets increase the intensity of your coaching, and the
session calls for a slightly larger rep range that can enrage your biceps pump.
The seated curls are accomplished via a shortened range of
movement, and might hence be done after the full-range standing
curls. Biceps workouts mostly include isolation workouts, which help build
muscle dimension and power that carry over to compound lifts.
Coaching gurus have long taught the bodybuilding lots the logic of working a smaller muscle group such as the biceps after a bigger muscle group like back,
or triceps after chest or shoulders. Whereas that is sensible,
if you’ve ever tried that arm exercise without preceding it with a
larger muscle group, then you know how intense—and pumped—your arms
can get if you practice them alone. The chest and bicep
exercise routine kicks off with bench presses before
moving to lighter isolation work. When it comes to constructing large
biceps and forearms, the rope hammer curl is an efficient isolation workout that targets the brachialis and brachioradialis.
Building a large, thick, detailed back isn’t a brand new thought revealed solely
to modern-day bodybuilders like Ronnie Coleman, Jay Cutler, and Phil
Heath. Arnold, Franco Columbu, and others they skilled with additionally knew the importance of the
again double-biceps and lat unfold poses for successful main competitions.
Biceps are not merely a muscle group; they’re symbolic of power and energy.
When people take into consideration fitness, the biceps often come to thoughts as the
ideal of a match physique. This muscle group has two primary heads – the
long head and the short head – each contributing
uniquely to the biceps’ look and function.
These workout routines add extra risk to harm due to
the high volume of seven sets. [newline]These barbell arm exercises are
highly recommended for anybody interested in building arm
muscular tissues and gaining strength. Barbell spider
curls train your biceps in a shortened (which is to say, a maximally
contracted) muscle position. This leads to a robust
muscle pump that may make your arms appear more vascular and result in significant hypertrophy.
If you’re on the lookout for straightforward barbell arm exercises to add to your routine, barbell curls are an excellent staple exercise to get
you started. If you need to construct larger arms utilizing a barbell, you must work out your biceps,
triceps, and forearms. That is why we now have selected workout routines that hit all of these muscle teams.
If your biceps look good when flexed but a bit thin when they’re relaxed, then you can do a particular lengthy head bicep
exercise to beef up the outer muscle fibers of your bis.
The first one of these curl variants is the Supinated Cross Body Curl, a unbelievable train which permits us to preferentially hit the long muscle heads of the biceps.
Slowly decrease the dumbbells, and squeeze the triceps on the bottom part
of the movement. In this challenging exercise both biceps and triceps might be working in an alternating
fashion. We know after we do that we can antagonistically shut off
the biceps, or a minimum of allow for a larger stretch of the biceps.
As A Result Of of the external rotation of the shoulder on this
motion, you additionally preferentially hit the inner portion of the biceps, which is the
internal head. We always need to begin off our coaching session with the ‘big exercise’ and move that heavier weight whereas we’ve probably the most
energy. Then we have the brachialis muscle, which is technically a separate muscle from
the biceps. However, it significantly influences the visible dimension of your biceps, and is the
important thing to getting wider biceps. Utilizing my handy Muscle Tissue
Markers I’ll present you the totally different main muscular tissues and
areas that make up the biceps muscle. If you actually need to take
your biceps development to the next stage,
you’re going to need to stimulate the bicep muscle in some
intense and extremely effective methods.
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