RU2589824C1 - Injectable composition based on group b vitamins and lidocaine - Google Patents

Abstract

FIELD: pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical industry and medicine and represents a pharmaceutical composition for parenteral administration in diseases and disorders associated with syndromes of nervous system of various origin, including from 4.5 to 6.25 wt% thiamine hydrochloride, from 4.5 to 5.5 wt% pyridoxine hydrochloride, from 0.045-0.055 % cyanocobalamin, from 0.9 to 1.1 wt% lidocaine hydrochloride, 0.105 to 0.095 wt% sodium hexapolyphosphate, from 0.95 to 1.05 wt% linear sodium polyphosphate, from 0.009-0.015 wt% potassium ferricinide (III), sodium hydroxide to pH 4.54 ± 0.05, from 1.8 to 2.2 wt% benzyl alcohol and water for injections - balance.

EFFECT: invention provides high stability of preparation for up to 2 years at temperature higher than 15 degrees Celsius, as well as avoiding formation of suspension in injection solution.

4 cl, 1 ex

Description

The invention relates to medicine, in particular to pharmacology, to an injection solution based on B vitamins and lidocaine, used as a pathogenetic and symptomatic agent in the treatment of diseases and syndromes of the nervous system of various origins.

Composition Composition:

(a) thiamine hydrochloride,

(b) pyridoxine hydrochloride,

(c) cyanocobolamine,

(d) lidocaine hydrochloride,

(i) sodium hexapolyphosphate and

(ii) linear sodium polyphosphate,

(k) potassium ferricyanide (III),

(l) sodium hydroxide,

(m) benzyl alcohol,

(n) water for injection,

while the pH of the prepared solution is 4.54 ± 0.05.

The components of the composition are well known in the art. Vitamin B ₁ (thiamine), in addition to the preventive and therapeutic effect with appropriate hypo- and vitamin deficiency, indications for the use of vitamin B ₁ are neuritis, radiculitis, neuralgia, peripheral paralysis, also used for dermatoses of neurogenic origin, pruritus of various etiologies, pyoderma, eczema, psoriasis.

Vitamin B ₁₂ (cyanocobalamin) is a growth factor and stimulator of hematopoiesis, has a beneficial effect on the functions of the liver and nervous system, activates blood coagulation, metabolism of carbohydrates and lipids, and is involved in the synthesis of various amino acids. Cyanocobalamin is a highly effective drug that helps with malignant anemia, posthemorrhagic (iron deficiency), alimentary and other types of anemia. It is also prescribed for radiation sickness, liver diseases (Botkin's disease, hepatitis, cirrhosis), for some diseases of the nervous system, infections, etc.

Vitamin B ₆ (pyridoxine) is used for B ₆ hypovitaminosis, toxicosis of pregnant women, anemia, leukopenia of various etiologies, diseases of the nervous system (parkinsonism, radiculitis, neuritis, neuralgia), a number of skin diseases, etc.

The listed neurotropic vitamins of group B have a beneficial effect in inflammatory and degenerative diseases of nerves and the motor apparatus, in high doses they have an analgesic effect, contribute to increased blood flow and normalize the functioning of the nervous system and the process of blood formation.

The chemical structure of lidocaine refers to acetanilide derivatives. It has a pronounced local anesthetic and antiarrhythmic (IB class) effect. The local anesthetic effect is due to inhibition of nerve conduction due to the blockade of sodium channels in the nerve endings and nerve fibers. In its anesthetic effect, lidocaine significantly (2-6 times) exceeds procaine; the effect of lidocaine develops faster and lasts longer - up to 75 minutes. When applied topically, it dilates blood vessels, does not have a locally irritating effect.

These B vitamins are included in the vitamin complex presented in patent RU 2225707 (CJSC Bryntsalov-A), in patent RU 2326669 (OJSC Moscow Chemical and Pharmaceutical Production Association named after N. A. Semashko), in addition, are known Milgamma®, Combilipen® and Kompligam® medicines based on a complex of vitamins B and lidocaine. However, due to the thermolability of vitamins, well-known drugs are compelled to be stored at low temperatures. Thus, the two-year stability of the drug is provided by a temperature of 2-8 ° C (domestic preparations) and 15 ° C at Milgamma®.

The objective of the present invention is to increase the stability of the drug up to 2 years or more at a storage temperature equal to or more than 15 ° C, as well as eliminating the possibility of suspension of the amount of suspension in the injection solution. The technical result of the invention is to increase the stability of the injection solution at a storage temperature of 15 ° C or more (up to 20 ° C on average) and stabilize the pH of the solution 4.54 ± 0.05.

The problem is solved by introducing into the composition a combination of sodium polyphosphates, consisting of hexapolyphosphate and linear polyphosphate, while the pH of the solution should correspond to 4.54 ± 0.05. A composition comprising a combination of polyphosphates has advantages over other compositions based on B vitamins and lidocaine in terms of stability and purity of the solution. However, the search for the necessary conditions for increasing the stability of the injection solution required a considerable amount of time and effort, because this composition of the composition is not obvious, which is clearly demonstrated by the formulations of finished drugs that do not have the necessary stability.

The present invention relates to injection compositions intended for use in medicine and veterinary medicine. The claimed injection composition includes the following components:

(a) thiamine hydrochloride,

(b) pyridoxine hydrochloride,

(c) cyanocobolamine,

(d) lidocaine hydrochloride,

(i) sodium hexapolyphosphate and linear sodium polyphosphate,

(k) potassium ferricyanide (III),

(l) sodium hydroxide,

(m) benzyl alcohol,

(n) water for injection,

while the pH of the prepared solution is 4.54 ± 0.05.

Due to the introduction of a combination of polyphosphates into the composition, the stability of the solution at a storage temperature of 15 ° C or more (on average up to 20 ° C) increases.

A preferred injection composition includes the following components:

(a) from 4.5 to 6.25 (wt.%) thiamine hydrochloride,

(b) from 4.5 to 5.5 (wt.%) pyridoxine hydrochloride,

(c) from 0.045 to 0.055 (wt.%) cyanocobalamin,

(d) from 0.9 to 1.1 (wt.%) lidocaine hydrochloride,

(i) from 0.095 to 0.105 (wt.%) sodium hexapolyphosphate and

(ii) from 0.95 to 1.05 (wt.%) linear sodium polyphosphate,

(k) from 0.009 to 0.015 (wt.%) potassium ferricyanide (III),

(l) sodium hydroxide to a pH of 4.54 ± 0.05,

(m) from 1.8 to 2.2 (wt.%) benzyl alcohol, water for injection - the rest.

It should be borne in mind that the amount of the substance of the composition during storage of the solution can correspond to any value in the range.

For thiamine hydrochloride it is 4.5; 4.6; 4.7; 4.8; 4.9; 5.0; 5.1; 5.2; 5.3; 5.4; 5.5; 5.6; 5.7; 5.8; 5.9; 6.0; 6.1; 6.2; 6.25 (wt.%).

For pyridoxine hydrochloride it is 4.5; 4.6; 4.7; 4.8; 4.9; 5.0; 5.1; 5.2; 5.3; 5.4; 5.5 (wt.%).

For cyancobalamin, this is 0.045; 0.046; 0.047; 0.048; 0.049; 0.050; 0.051; 0.052; 0,053; 0,054; 0.055 (wt.%).

For lidocaine hydrochloride it is 0.9; 1.0; 1.1 (wt.%).

For sodium hexapolyphosphate it is 0,095; 0.096; 0.097; 0.098; 0.099; 0,100; 0.101; 0.102; 0.103; 0.104; 0.105 (wt.%).

For linear polyphosphate, this is 0.095; 0.096; 0.097; 0.098; 0.099; 0.10; 0.101; 0.102; 0.103; 0.104; 0.105 (wt.%).

For potassium ferricinide (III), it is 0.009; 0.010; 0.011; 0.012; 0.014; 0.015 (wt.%).

For benzyl alcohol it is 1.8; 1.9; 2.0; 2.1; 2.2 (wt.%).

Even more preferred are the above compositions, which include linear polyphosphates with a degree of polymerization of the order of 25.

Particularly preferred are compositions prepared as an intramuscular injection.

The finished compositions are applicable to animals and humans for diseases and disorders associated with syndromes of the nervous system of various origins: neuropathies and polyneuropathies (diabetic, alcoholic and others); neuritis and polyneuritis, including retrobulbar neuritis; peripheral paresis, including facial nerve; neuralgia, including trigeminal nerve and intercostal nerves; pain caused by diseases of the spine (intercostal neuralgia, lumbar ischialgia, lumbar syndrome, cervical syndrome, cervicobrachial syndrome, radicular syndrome caused by degenerative changes in the spine); plexopathy, ganglionitis (including herpes zoster).

Although the invention is presented in this document taking into account various typical practical methods of application, it should be borne in mind that these options for practical application are only a description of the principles of the existing invention and its application. Specialists who are experts in this field of knowledge can see that there may be many modifications of typical variants of the practical application of the invention, not beyond the scope of the invention.

In addition, it should be borne in mind that various features and / or characteristics of different methods of practical application of the invention can be combined. Therefore, it should be understood that numerous modifications may exist in addition to the described practical applications, and other methods of use may be devised that are not outside the scope of the invention.

In addition, specialists in a specific field of specialized knowledge can see other options for the practical application of the invention after reading the description of the invention, as well as after the practical use of the invention presented in this document. It is assumed that the description sections and examples will be taken only as an illustration of a typical application, in accordance with this field of knowledge and the indications of this application for invention.

Example 1. Obtaining an injection composition based on vitamins of group B and lidocaine.

1. Water for injection is loaded into the reactor, bubbling is switched on and cooling water is supplied to the reactor jacket;

2. When a temperature of about 40 ° C is reached, potassium hexacyanoferrate and benzyl alcohol are loaded into the reactor; when bubbling is on, the reactor remains for about 12 hours;

3. Milestones of the remaining ingredients are being loaded except sodium hydroxide;

4. After dissolving all the components, sodium hydroxide is loaded to bring the solution to pH = 4.54.

The reactor is purged with nitrogen at all stages, including filling the solution into ampoules.

Claims (4)

1. A pharmaceutical composition for parenteral administration in diseases and disorders associated with syndromes of the nervous system of various origins, comprising the following components:
(a) from 4.5 to 6.25 (wt.%) thiamine hydrochloride,
(b) from 4.5 to 5.5 (wt.%) pyridoxine hydrochloride,
(c) from 0.045 to 0.055 (wt.%) cyanocobalamin,
(d) from 0.9 to 1.1 (wt.%) lidocaine hydrochloride,
(i) from 0.095 to 0.105 (wt.%) sodium hexapolyphosphate and
(ii) from 0.95 to 1.05 (wt.%) linear sodium polyphosphate,
(k) from 0.009 to 0.015 (wt.%) potassium ferricinide (III),
(l) sodium hydroxide to a pH of 4.54 ± 0.05,
(m) from 1.8 to 2.2 (wt.%) benzyl alcohol, water for injection - the rest. 2. The pharmaceutical composition for parenteral administration according to claim 1, wherein the linear sodium polyphosphate has a degree of polymerization of about 25. 3. The pharmaceutical composition for parenteral administration according to claim 1, obtained in the form of an injection solution for intramuscular administration. 4. The use of the pharmaceutical composition for parenteral administration according to claim 1 for the prevention or treatment of diseases and disorders associated with syndromes of the nervous system of various origins.