DE1299796B - Surface anesthetic - Google Patents

Description

1 2

The invention relates to a surface anesthetic tylaminobenzoyl-dimethylaminoethanol and n-butyl

with low toxicity. arrüno ^ -methyl-ö-chloroacetanilide and on the other hand Hy-

It is known to use injectable local anesthetics as droxyäthoxypolyäthoxydodecan, Hydroxyäthoxypoly-

Use surface anesthetics. Examples of this are ethoxybenzene and hydroxyethoxypolyethoxyoctenyl Contains cocaine, tetracaine, butanilicaine, lidocaine and 5-dimethylbenzene in a ratio of 2: 1 to 1: 3,

Mepivacaine hydrochloride. the latter compounds 4 to

Contain a common identifier for the 16 ethoxy groups mentioned.

Injectable local anesthetics is that they have been shown in certain experiments that the so obtained Degrees are toxic. When used as a surface anesthetic, when using an injectable local anesthetic for example, on the skin or on mucous agents in a concentration that does not have epidermis are to be used, it can happen that surface anesthesia results, and this with an Oberdaß they are to be used on large surfaces, surface anesthetic added to the above formula, and large quantities are then required. Doing so has an effect that is toxic in terms of toxicity it is desirable that the concentration of the citizen be significantly better than that of the cited ones Local anesthetic with regard to toxicity 15 surface anesthetics.

is kept as low as possible. That means, the two starting points can be appropriate

that the duration of action is noticeably reduced Solvents, for example water, are dissolved,

and in many cases not the required value and one may well be suitable for the new remedy

achieved. Accordingly, it is desirable to use the active carrier substances, so that an ointment, a

20 gel or lozenge is obtained while maintaining low toxicity,

gladly. The toxicity thus sets the upper limit for the. The surprising increase in effectiveness occurs with the

Duration of action of the injectable local anesthetics. already mentioned ratio of 2: 1 to 1: 3 and

Concentrations higher than 4% are allowed in terms of having an optimum at a molecular ratio of the

should not be used on toxicity if possible. Components of 1: 1. If this ratio changes

It is also known that as surface anesthetics the increase in effectiveness decreases again.

Compounds of the general formula The method according to the present invention

R - (OCH ₂ CH ₂₎ - OCH ₂ CH ₂ OH ^{is carried f} ° ^{lgende Beispide veransc "ht} ·

to use, in which R is an alkyl, an aryl or example 1

an alkylaryl group with at most 20 carbon 30

atoms and at least 6 carbon atoms or 0.25 g of l-methyl-2-piperidinecarboxylic acid-2,6-dimen-

preferably with a maximum of 16 carbon atoms and thylanilide in powder form and 0.25 g of hydroxyethoxy means at least 8 carbon atoms and η a polyethoxydodecane in oil form and with a molecular weight between 4 and 16 or preferably between 6 and 14 kular weight of about 600 are in 100 g of distilling value. 35 lated water with isotonic addition of table salt

The connections mentioned have been solved very little. If 0.25 ml of this liquid becomes toxic to a, but has the disadvantage that its anesthetic rabbit cornea is applied, a host depth is obtained which is unsatisfactory. The connections last about 20 minutes. A 0.25 ° / ₀ strength may not be in a higher concentration than 6 ° / ₀ solution used 2-piperidinecarboxylic acid, 2,6-diwerden l-methyl-of, as otherwise side reactions dermatological 40 provides methylanilide can occur when applying a rabbit functions. In most cases it is advisable not to go below the cornea and, with an amount of 0.25 ml, the effect should not fall below a concentration of 2%. duration 0. A concentration of 0.25% hydroxy-It is also advisable not to exceed a molecular weight of ethoxypolyethoxydodecane when applied of 800 and also not to fall below that of a rabbit cornea and a molecular weight of 500 for an amount. 45 0.25 ml lasts 10 minutes, with a

When preparing compounds according to the amount of 0.1 ml, a duration of action of 9 minutes, general formula, it shows that one

Mixture gets, in the η of the different loading Example2

constituents one within the stated limits

has cherishing value. One can, of course, replace 0.25 g of 1-methyl-2-piperi compound in Example 1, in which η has a desired 2,6-dimethylanilide by 0.50 g of 1-Me value, but mostly the mixture is used as such, thyl-2-piperidinecarboxylic acid-2,6-dimethylanilide. a preparation made on the rabbit cornea

Tests have now shown that if you give a duration of action of 21.2 minutes. 0.50 ° / ₀ strength of the surface anesthesia certain injectable Lo 55 solution of l-methyl - ^ - ^ o-piperidinecarboxylic dikalanästhetika or salts thereof in a concen- methylanilide indicates the Kaninchencornea the host ration, the effect duration toxicity within acceptable limits 0 . keeps using certain surface anesthetics after the

mentioned formula in a concentration that does not include example 3

Give rise to side reactions, offset, surface 60

anesthetics is obtained with an effect similar to that in Example 1 0.25 g of l-methyl-2-piperidine

Total effect of the two preparations exceeds. carboxylic acid-2,6-dimethylanilide by 0.25 g ω-di-

A surface anesthetic according to the invention replaces ethylamino-2,6-dimethylacetanilide, is obtained in that, on the one hand, it contains 1-methyl- a preparation which, on the rabbit cornea, a We-2-piperidinecarboxylic acid-2,6-dimethylanilide, <w- Diethyl 65 kungs duration of 18.9 minutes results. A 0.25 ° / ₀ strength amino-2,6-dimethylacetanilide, 2-Diäthylaminoäthyl- solution of o) -Diäthylamino-2,6-dimethylacetanilide ester of p-aminobenzoic acid, (l-Methyl-5-ethyl results in a Rabbit cornea test an action-2-piperidinecarboxylic acid) -2,4,6-trimethylanilide, p-Bu- duration 0.

Example 4

If, in Example 1, 0.25 g of l-methyl-2-piperidinecarboxylic acid-2,6-dimethylanilide is replaced by 0.10 g of the 2-diethylaminoethyl ester of p-aminobenzoic acid, a preparation is obtained which, in the rabbit cornea test, has a duration of action of 18, 4 minutes results. A 0, l ° / ₀ solution of said ester is the duration of action when 0 Kaninchencorneatest.

Example5

If, in example 1, 0.25 g of hydroxyethoxypolyethoxydodecane is replaced by 0.25 g of hydroxyethoxypolyethoxybenzene, a preparation is obtained which has an effect of 14.5 minutes in the rabbit cornea test results. A potentiation is obtained because the anesthetic agents in question only have one duration of action of 0 or 6.5 minutes.

Example 6

If, in Example 1, 0.25 g of hydroxyethoxypolyethoxydodecane is replaced by 0.25 g of hydroxyethoxypolyethoxyoctenyldimethylbenzene, a preparation is obtained which has a duration of action of 15.3 minutes in the rabbit cornea test. A concentration of 0.25% Hydroxyäthoxypolyäthoxyoctenyldimethylbenzol gives in the same test a duration of action of only 4.5 minutes.

Example 7

If, in Example 1, the injectable local anesthetic is replaced by 0.1 g (1-methyl-S-ethyl ^ -piperidinecarboxylic acid) -2,4,6-trimethylanilide, a preparation is obtained which has a duration of action of 21.0 minutes in the cornea test results. A potentiation is obtained because the anesthetic agents in question only have a duration of action of 0 or 6.5 minutes. Experiments have also shown that a 0.3 ° / ₀ solution of Hydroxyäthoxypolyäthoxytetradecan with either 0, l ° / ₀ sodium p-Butylaminobenzoyl-dimethylaminoethanol, or with 0.2% n-butylamino-2-methyl-6-chloroacetanilide can be moved, whereby a usable surface anesthetic is obtained, the effect of which corresponds approximately to the double effect of Hydroxyäthoxypolyäthoxytetradecan.

Claims (1)

Claim: Surface anesthetic, characterized in that it contains 1-methyl-2 -piperidincarbonsäiire -2,6 - dimethylanilide, ω - diethylamino - 2,6 - dimethylacetanilide, 2 - diethylaminoethyl ester of p-aminobenzoic acid (1-methyl - 5 - ethyl - 2 - piperidinecarboxylic acid) -2,4,6 - trimethylanilide, p-butylaminobenzoyldimethylaminoethanol and n-butylamino ^ -methyl-ö -chloroacetanilide and on the other hand Hydroxyäthoxypolyäthoxydodecan, Hydroxyäthoxypolyäthoxybenzol and Hydroxyäthoxypolyäthoxyoctenyldimethylbenzol in a ratio of 2: 1 to 1: 3, the the last-mentioned compounds contain 4 to 16 ethoxy groups.