PT101388B - THEMATIC ACID INFUSION SOLUTIONS IN THE FORM OF ITS SOLUTIONS IN WATER AND AMPOLA FOR PARENTERAL APPLICATION - Google Patents
THEMATIC ACID INFUSION SOLUTIONS IN THE FORM OF ITS SOLUTIONS IN WATER AND AMPOLA FOR PARENTERAL APPLICATION Download PDFInfo
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- PT101388B PT101388B PT101388A PT10138893A PT101388B PT 101388 B PT101388 B PT 101388B PT 101388 A PT101388 A PT 101388A PT 10138893 A PT10138893 A PT 10138893A PT 101388 B PT101388 B PT 101388B
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- thioctic acid
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- water
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- parenteral application
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- 239000003978 infusion fluid Substances 0.000 title claims description 7
- 239000000243 solution Substances 0.000 title description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title description 6
- 239000002253 acid Substances 0.000 title 1
- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 claims description 33
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 claims description 32
- 235000019136 lipoic acid Nutrition 0.000 claims description 32
- 229960002663 thioctic acid Drugs 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 10
- 239000003708 ampul Substances 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- 239000007924 injection Substances 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- 238000007872 degassing Methods 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000008215 water for injection Substances 0.000 description 4
- 238000011109 contamination Methods 0.000 description 3
- XZUAPPXGIFNDRA-UHFFFAOYSA-N ethane-1,2-diamine;hydrate Chemical compound O.NCCN XZUAPPXGIFNDRA-UHFFFAOYSA-N 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000011148 porous material Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 229960000281 trometamol Drugs 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- HXKKHQJGJAFBHI-UHFFFAOYSA-N 1-aminopropan-2-ol Chemical compound CC(O)CN HXKKHQJGJAFBHI-UHFFFAOYSA-N 0.000 description 1
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 1
- 208000003130 Alcoholic Neuropathy Diseases 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 208000005374 Poisoning Diseases 0.000 description 1
- 206010036106 Polyneuropathy alcoholic Diseases 0.000 description 1
- WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 208000020701 alcoholic polyneuropathy Diseases 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 125000005263 alkylenediamine group Chemical group 0.000 description 1
- 150000004716 alpha keto acids Chemical class 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 229960003624 creatine Drugs 0.000 description 1
- 239000006046 creatine Substances 0.000 description 1
- 150000001923 cyclic compounds Chemical class 0.000 description 1
- 201000002342 diabetic polyneuropathy Diseases 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 235000010299 hexamethylene tetramine Nutrition 0.000 description 1
- 239000004312 hexamethylene tetramine Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- ZYTYOUNYLKOKAR-UHFFFAOYSA-N morpholine;pyrrolidine Chemical compound C1CCNC1.C1COCCN1 ZYTYOUNYLKOKAR-UHFFFAOYSA-N 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 238000005895 oxidative decarboxylation reaction Methods 0.000 description 1
- 125000005429 oxyalkyl group Chemical group 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 229940005605 valeric acid Drugs 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
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/385—Heterocyclic compounds having sulfur as a ring hetero atom having two or more sulfur atoms in the same ring
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
DESCRIÇÃODESCRIPTION
SOLUÇÕES DE INFUSÃO DE ÁCIDO TIOCTICO SOB A FORMA DOS ! SEUS SAIS SOLÚVEIS EM ÁGUA E AMPOLA PARA APLICAÇÃOTHIOCTIC ACID INFUSION SOLUTIONS IN THE FORM OF! ITS WATER-SOLUBLE SALTS FOR APPLICATION
PARENTERALPARENTERAL
O ácido alfa-lipónico (ácido tioctico) é quimicamente um ácido 1,2-ditiaciclopentano· valérico:Alpha-liponic acid (thioctic acid) is chemically 1,2-dithiaciclopentane · valeric acid:
s — ss - s
O ácido tioctico é um componente do metabolismo celular e encontra-se por isso em muitos organismos vegetais e animais. Actua como um dos coenzimas na descarboxilação oxidativa do piruvato e de outros alfa-cetoácidos.Thioctic acid is a component of cellular metabolism and is therefore found in many plant and animal organisms. It acts as one of the coenzymes in the oxidative decarboxylation of pyruvate and other alpha-keto acids.
O ácido tioctico emprega-se desde há muito tempo em várias doenças, nomeadamente em doenças do fígado, no caso de lesões hepáticas provocadas por envenenamento com ί, cogumelos, bem como no caso da polineuropatia diabética e alcoólica, uma das alterações do ; sistema nervoso central relacionadas com as doenças do metabolismo.Thioctic acid has been used for a long time in several diseases, namely liver diseases, in the case of liver damage caused by poisoning with ί, mushrooms, as well as in the case of diabetic and alcoholic polyneuropathy, one of the alterations of; central nervous system related to diseases of metabolism.
Na terapia com ácido tioctico utiliza-se a solução injectável, principalmente no estado : inicial do tratamento. As soluções até agora disponíveis tinham contudo a desvantagem de não serem óptimas do ponto de vista da assimilibilidade. Há queixas de pacientes em relação a dores durante a injecção e ainda a ardores no local de injecção.In therapy with thioctic acid, the solution for injection is used, mainly in the initial treatment stage. The solutions available until now, however, had the disadvantage of not being optimal from the point of view of assimilability. There are complaints from patients about pain during the injection and also about burning at the injection site.
O processo usual de administração, pelo médico ou por pessoal auxiliar especializado, consistia em diluir de modo adequado a solução injectável disponível no mercado e injectar em seguida a solução diluída obtida.The usual administration procedure, by the doctor or by specialized auxiliary personnel, consisted of adequately diluting the injectable solution available on the market and then injecting the diluted solution obtained.
A DE-OS 38 40 076 descreve uma solução injectável de sais de ácido tioctico, com Trometamol como agente de formação de sal, sem referir o problema da segurança de manipulação.DE-OS 38 40 076 describes a solution for injection of salts of thioctic acid, with Trometamol as a salt forming agent, without mentioning the problem of safe handling.
-1rápida quanto possível. Ao encontro desta necessidade vêm as soluções de injecção ou difusão que sejam estáveis no armazenamento e directamente utilizáveis sem diluições complicadas (forma ready-to-use). Na sua utilização poupa-se, por um lado, trabalho de preparação, j aumentando-se, por outro lado, a segurança do medicamento. Não existe assim o perigo de enganos devidos a soluções mal etiquetadas, devendo as soluções ser correctamente rotuladas após as diluições. Além disso, reduz-se o risco de contaminação por métodos de trabalho não ji li esterilizados na abertura das ampolas, retirada da solução das várias ampolas e injecção na solução de diluição. Estas fases de processamento não são necessárias no caso de soluções prontas a utilizar.-1fast as possible. This solution comes with injection or diffusion solutions that are stable in storage and directly usable without complicated dilutions (ready-to-use form). Its use saves, on the one hand, preparation work, while increasing, on the other hand, the safety of the medicine. Thus, there is no danger of mistakes due to poorly labeled solutions, and the solutions must be correctly labeled after dilutions. In addition, the risk of contamination by non-sterile working methods is reduced when opening the ampoules, removing the solution from the several ampoules and injecting the dilution solution. These processing steps are not necessary for ready-to-use solutions.
Como outras vantagens mencionam-se a maior facilidade e estabilidade de armazenamento e os menores custos de gestão na farmácia.Other advantages include greater ease and stability of storage and lower management costs at the pharmacy.
O objectivo da presente invenção é por isso uma solução de ácido cc-lipónico, na forma dos seus sais solúveis em água, com uma concentração de 0,4 - 16 g por litro.The object of the present invention is therefore a solution of cc-liponic acid, in the form of its water-soluble salts, with a concentration of 0.4 - 16 g per liter.
Na terapia com ácido tioctico utiliza-se a solução injectável, principalmente no estado inicial do tratamento. As ampolas até agora disponíveis, contendo a solução injectável, têm uma dosagem máxima de 250 mg de ácido tioctico. A aplicação por administração é contudo de 600 mg como dose unitária.In therapy with thioctic acid the solution for injection is used, mainly in the initial stage of treatment. The ampoules available so far, containing the solution for injection, have a maximum dosage of 250 mg of thioctic acid. However, application per administration is 600 mg as a unit dose.
ΗΗ
Isto significa para o médico, que ele tem de abrir várias ampolas, medir o seu conteúdo | e reuni-lo num único recipiente, e só depois pode iniciar a aplicação. Esta manipulação é ! incómoda, uma vez que a solução tem de ser retirada das várias ampolas com o auxílio de uma ;j cânula. Dado que se têm de abrir primeiro todas as ampolas e só depois se retira a solução, íi existe o perigo de as ampolas já abertas e colocadas sobre uma base serem derrubadas por desatenção, perdendo-se o seu conteúdo, sendo este modo de manipulação a causa de contaminações.This means that the doctor has to open several ampoules, measure their contents | and assemble it in a single container, and only then can you start the application. This manipulation is! annoying, since the solution has to be removed from the various ampoules with the aid of a cannula. Since all the ampoules have to be opened first and then the solution is withdrawn, there is a danger that the ampoules that are already open and placed on a base will be dropped by inattention, losing their content, this way of handling being cause of contamination.
Uma vez que se sabe que o pessoal auxiliar que se ocupa destas actividades nos hospitais se toma cada vez mais escasso, há a necessidade de conseguir agentes terapêuticos tão ί fáceis e rápidos de manusear quanto possível. Esta necessidade consegue satisfazer-se com i uma forma de administração que contenha a quantidade total de solução injectável a aplicar num único recipiente. Um outro objectivo da presente invenção é por isso uma ampola ou um frasco perfúrável que contém 300-800 mg de ácido tioctico. Nestes recipientes, o ácido tioctico H encontra-se na forma de um dos seus sais. Como agentes para a formação de sais referem-se, i por exemplo, as bases ou catiões usuais que sejam fisiologicamente assimiláveis na forma deSince it is known that the auxiliary staff who are engaged in these activities in hospitals is becoming increasingly scarce, there is a need to obtain therapeutic agents as easy and quick to handle as possible. This need is able to satisfy itself with a form of administration that contains the total amount of solution for injection to be applied in a single container. Another object of the present invention is therefore an ampoule or a perforable vial containing 300-800 mg of thioctic acid. In these containers, thioctic acid H is in the form of one of its salts. The agents for the formation of salts include, for example, the usual bases or cations that are physiologically assimilable in the form of
-2No manuseamento de uma das formas de administração acima referidas são de facto necessárias menos manipulações, o que diminui o risco de uma contaminação bacteriana com : todas as consequências dela resultantes. Abre-se a ampola, retira-se a solução e injecta-se ou adiciona-se a uma solução suporte para diluição e, em seguida, iníúnde-se a solução resultante. O risco de mistura com outras ampolas abertas ao mesmo tempo é nulo.-2When handling one of the aforementioned forms of administration, fewer manipulations are in fact required, which reduces the risk of bacterial contamination with: all the consequences resulting from it. The ampoule is opened, the solution is withdrawn and injected or added to a dilution support solution, and then the resulting solution is added. The risk of mixing with other open ampoules at the same time is zero.
ii
O pH das soluções de acordo com a invenção ajusta-se a um valor básico de 7,6 a ; cerca de 8,8, utilizando um excesso de componentes básicos, isto é, uma quantidade superior à i equimolar. íThe pH of the solutions according to the invention is adjusted to a basic value of 7.6 a; about 8.8, using an excess of basic components, that is, an amount greater than equimolar i. í
Exemplos destes componentes básicos, são os seguintes:Examples of these basic components are as follows:
Π iΠ i
Metais alcalinos e alcalinoterrosos, hidróxido de amónio, aminoácidos básicos como arginina e lisina, aminas de fórmula NRjRjR,, em que os grupos Rp R, e R, são iguais ou ! diferentes e significam hidrogénio, alquilo-C^-C^ ou oxialquilo-C^C^, como por exemplo ; mono- e di-etanolamina, l-amino-2-propanol, 3-amino-l-propanol; alquilenodiaminas com uma cadeia de alquileno com 2 a 6 átomos de carbono, como etilenodiamina ou hexametílenotetramina; compostos anunados cíclicos saturados com 4 a 6 átomos de carbono i j; no anel, como piperidina, piperazina, pirrolidino-morfolina, N-metilglucamina, creatina e ! trometamol.Alkali and alkaline earth metals, ammonium hydroxide, basic amino acids such as arginine and lysine, amines of the formula NRjRjR ,, in which the groups R p R, and R, are the same or! different and mean hydrogen, C1 -C4 alkyl, or C4-C4 oxyalkyl, as for example; mono- and di-ethanolamine, 1-amino-2-propanol, 3-amino-1-propanol; alkylene diamines with an alkylene chain having 2 to 6 carbon atoms, such as ethylenediamine or hexamethylenetetramine; dyed cyclic compounds saturated with 4 to 6 carbon atoms ij; in the ring, such as piperidine, piperazine, pyrrolidine-morpholine, N-methylglucamine, creatine and! trometamol.
í i As soluções podem preparar-se, conforme o caso, com adição de outras substâncias de j pressão osmótica igual à do sangue. Para tal, podem empregar-se, por exemplo, as seguintes í substâncias:i i The solutions can be prepared, as appropriate, with the addition of other substances of osmotic pressure equal to that of the blood. For this purpose, the following substances can be used, for example:
ii
II
Cloreto de sódio, álcoois de açúcar como sorbitol, xilol ou manitol ou glucose. Adiciona-se uma quantidade das substâncias mencionadas tal que o abaixamento do ponto de congelação da solução seja igual ao abaixamento do ponto de congelação dos fluidos corporais (0,52 a 0,56°C).Sodium chloride, sugar alcohols such as sorbitol, xylol or mannitol or glucose. An amount of the mentioned substances is added such that the lowering of the freezing point of the solution is equal to the lowering of the freezing point of body fluids (0.52 to 0.56 ° C).
;Í; Í
A concentração do ácido tioctico (na forma dos seus sais solúveis em água) é de 0,4 a 16 g/litro, de preferência de 1,6 a 10 g/litro, e em especial de 2,4 a 6 g/litro.The concentration of thioctic acid (in the form of its water-soluble salts) is 0.4 to 16 g / liter, preferably 1.6 to 10 g / liter, and in particular 2.4 to 6 g / liter .
ii
A quantidade de ácido tioctico numa ampola situa-se entre 300 mg e 800 mg.The amount of thioctic acid in an ampoule is between 300 mg and 800 mg.
-3Exemplo 1-3Example 1
Solução de infusão de ácido tioctico com 2,4 g de ácido tioctico por litro liInfusion solution of thioctic acid with 2.4 g of thioctic acid per liter li
Suspendem-se 0,6 Kg de ácido tioctico em 100 1 de água para injecções, intensivamente desgasificada com azoto. A esta suspensão adicionam-se 0,21 Kg de hidrato de ί etilenodiamina. Em seguida, agita-se até à dissolução do ácido tioctico, sob desgasificação I I contínua com azoto. A esta solução adicionam-se 2,0 Kg de cloreto de sódio, dissolvem-se sob I . agitação e perfaz-se o volume a 250 litros com água para injecções, sob desgasificação contínua com azoto. Filtra-se a solução através de um filtro de membrana de 0,22 pm de tamanho de poros e coloca-se em frascos de infusão de 250 ml, sob condições assépticas.0.6 kg of thioctic acid are suspended in 100 l of water for injections, intensively degassed with nitrogen. To this suspension is added 0.21 kg of ethylene diamine hydrate. Then, stir until thioctic acid dissolves, under continuous degassing with nitrogen. To this solution are added 2.0 kg of sodium chloride, dissolved under I. stirring and make up to 250 liters with water for injections, under continuous degassing with nitrogen. The solution is filtered through a 0.22 pm pore size membrane filter and placed in 250 ml infusion bottles under aseptic conditions.
I ί' Procede-se à desgasificação com azoto antes e depois do enchimento. Cada recipiente contémI ί 'Degassing with nitrogen before and after filling. Each container contains
600 mg de ácido tioctico na forma de sal de etilenodiamina.600 mg of thioctic acid in the form of ethylenediamine salt.
ί i iiί i ii
Exemplo 2Example 2
I ií Solução de infusão de ácido tioctico com 12 g de ácido tioctico por litro i iI ií Thioctic acid infusion solution with 12 g of thioctic acid per liter i i
Suspendem-se 0,6 Kg de ácido tioctico em 40 1 de água para injecções, intensivamente j ji desgasificada com azoto. A esta suspensão adicionam-se 0,21 Kg de hidrato de etilenodiamina. I0.6 kg of thioctic acid are suspended in 40 l of water for injections, intensively degassed with nitrogen. To this suspension is added 0.21 kg of ethylenediamine hydrate. I
Em seguida, agita-se até à dissolução do ácido tioctico, sob desgasificação contínua com azoto, i A esta solução adicionam-se 0,13 Kg de cloreto de sódio, dissolvem-se sob agitação e perfazii se o volume a 50 litros com água para injecções, sob desgasificação contínua com azoto. Filtrase a solução através de um filtro de membrana de 0,22 pm de tamanho de poros e coloca-se em frascos de infusão de 50 ml, sob condições assépticas. Procede-se à desgasificação com azoto antes e depois do enchimento. Cada recipiente contém 600 mg de ácido tioctico na forma de sal de etilenodiamina.Then, stir until thioctic acid dissolves, under continuous degassing with nitrogen. To this solution, 0.13 kg of sodium chloride are added, dissolved under agitation and the volume is made up to 50 liters with water. for injections, under continuous degassing with nitrogen. The solution is filtered through a 0.22 pm pore size membrane filter and placed in 50 ml infusion bottles under aseptic conditions. Degassing with nitrogen is carried out before and after filling. Each container contains 600 mg of thioctic acid in the form of ethylenediamine salt.
I i; Exemplo 3I i; Example 3
Ampolas de ácido tiocticoAmpoules of thioctic acid
Suspendem-se 10 Kg de ácido tioctico em 330 I de água para injecções, intensivamente desgasificada com azoto. A esta suspensão adicionam-se 3,53 Kg de hidrato de etilenodiamina e perfaz-se o volume da solução resultante a 400 litros, sob desgasificação contínua com azoto.10 kg of thioctic acid are suspended in 330 l of water for injections, intensively degassed with nitrogen. To this suspension are added 3.53 kg of ethylenediamine hydrate and the volume of the resulting solution is made up to 400 liters, under continuous degassing with nitrogen.
-4Após mistura intensiva filtra-se a solução através de um filtro de membrana de 0,22 um de tamanho de poros e coloca-se em ampolas ou frascos perfuráveis de 24 ml cada, sob condições assépticas. Procede-se à desgasificação com azoto antes e depois do enchimento. Cada recipiente contém 600 mg de ácido tioctico na forma de sal de etilenodiamia.-4After intensive mixing, the solution is filtered through a 0.22 µm pore size membrane filter and placed in perforated ampoules or flasks of 24 ml each, under aseptic conditions. Degassing with nitrogen is carried out before and after filling. Each container contains 600 mg of thioctic acid in the form of ethylene diamine salt.
Claims (5)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE9213914U DE9213914U1 (en) | 1992-10-15 | 1992-10-15 | Ampoule and infusion solution of thioctic acid in the form of the water-soluble salts of thioctic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PT101388A PT101388A (en) | 1994-09-30 |
| PT101388B true PT101388B (en) | 1999-09-30 |
Family
ID=6884846
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT101388A PT101388B (en) | 1992-10-15 | 1993-10-14 | THEMATIC ACID INFUSION SOLUTIONS IN THE FORM OF ITS SOLUTIONS IN WATER AND AMPOLA FOR PARENTERAL APPLICATION |
Country Status (7)
| Country | Link |
|---|---|
| BE (1) | BE1007420A3 (en) |
| DE (1) | DE9213914U1 (en) |
| ES (1) | ES2063713B1 (en) |
| FR (1) | FR2696933B3 (en) |
| IT (1) | IT1260996B (en) |
| NL (1) | NL9301781A (en) |
| PT (1) | PT101388B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4433764A1 (en) * | 1994-09-22 | 1996-03-28 | Asta Medica Ag | Dosage forms containing alpha-lipoic acid, solid salts of R-thioctic acid with improved release and bioavailability |
| DE29506604U1 (en) * | 1995-04-25 | 1995-06-14 | Asta Medica Ag, 01277 Dresden | Ready infusion set |
| ITMI20111975A1 (en) * | 2011-10-28 | 2013-04-29 | Labomar S R L | COMPOSITIONS INCLUDING A SALT OF AN ORGANIC ACID. |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1095991B (en) * | 1959-05-09 | 1960-12-29 | Chemiewerk Homburg Zweignieder | Process for the preparation of a stable and injectable solution containing 1,2-dithia-cyclopentane-3-valeric acid |
| JPS3814940B1 (en) * | 1961-03-04 | 1963-08-15 | ||
| JPS3922715B1 (en) * | 1962-03-29 | 1964-10-13 | ||
| DE1668887B2 (en) * | 1968-03-15 | 1976-06-16 | CA SALT OF 1,2-DITHIA-CYCLOPENTANE - EQUAL 3- VALERIAN ACID (THIOCTIC ACID) | |
| JPS4526516B1 (en) * | 1968-07-08 | 1970-09-01 | ||
| JPS6066955A (en) * | 1983-09-19 | 1985-04-17 | Kiyaraban:Kk | Preparation of dressing |
| IT1213141B (en) * | 1984-02-17 | 1989-12-14 | Dobrivoje Tomic | PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF DIABETES AND DISEASES AND HEPATIC DYSFUNCTIONS. |
| DE3512911A1 (en) * | 1985-04-11 | 1986-10-16 | Degussa Ag, 6000 Frankfurt | METHOD FOR PRODUCING 1,2-DITHIOLAN-3-PENTANIC ACID (THIOCTSAEURE) |
| EP0318891B1 (en) * | 1987-12-04 | 1992-01-02 | ASTA Medica Aktiengesellschaft | Injectable solution of thioctic acid containing trometamole and/or basic amino acids |
| US5334612A (en) * | 1988-11-09 | 1994-08-02 | Asta Pharma Aktiengesellschaft | Pharmaceutical compositions containing as active substance sulphur-containing carboxylic acids and their use in combating retroviruses |
| DE4035442B4 (en) * | 1989-11-09 | 2010-04-29 | Evonik Degussa Gmbh | Medicaments containing as active ingredient R-α-lipoic acid |
-
1992
- 1992-10-15 DE DE9213914U patent/DE9213914U1/en not_active Expired - Lifetime
-
1993
- 1993-09-03 BE BE9300910A patent/BE1007420A3/en not_active IP Right Cessation
- 1993-09-16 FR FR9311052A patent/FR2696933B3/en not_active Expired - Lifetime
- 1993-10-14 PT PT101388A patent/PT101388B/en not_active IP Right Cessation
- 1993-10-14 ES ES09302159A patent/ES2063713B1/en not_active Expired - Fee Related
- 1993-10-14 NL NL9301781A patent/NL9301781A/en active Search and Examination
- 1993-10-15 IT ITTO930761A patent/IT1260996B/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| DE9213914U1 (en) | 1992-12-03 |
| ES2063713A1 (en) | 1995-01-01 |
| ITTO930761A1 (en) | 1995-04-15 |
| IT1260996B (en) | 1996-04-29 |
| BE1007420A3 (en) | 1995-06-13 |
| ITTO930761A0 (en) | 1993-10-15 |
| FR2696933A3 (en) | 1994-04-22 |
| PT101388A (en) | 1994-09-30 |
| FR2696933B3 (en) | 1994-09-23 |
| NL9301781A (en) | 1994-05-02 |
| ES2063713B1 (en) | 1995-07-16 |
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