Anesthetic composition for topical administration comprising lidocaine, prilocaine and tetracaine

Abstract

It comprises a mixture of lidocaine, prilocaine and tetracaine, or their pharmaceutically acceptable salts. The preferred composition comprises the following components in the indicated approximate w / w percentages: 1.5% of lidocaine base; 1.5% of prilocaine base; 4% of tetracaine base; 10% of methylpynrolidone; 2% of dimethyl sulfoxide; 0.08% of topical hyaluronidase; 1.5% of guar gum; 1% of Tween-20; 0.5% of Tween-80, and the necessary amount of water to 100%. It exhibits a a high concentration on skin, a deep anesthetic effect and a significantly more rapid onset of the anesthetic effect than comparable transdermal anesthetics.

Description

[0001] This invention relates to the field of human medicine, and specifically to topical anesthetic formulations which include mixtures of several anesthetic agents. BACKGROUND ART [0002] Surgical techniques can only be performed after the highly sensitive nerve endings in the skin are anesthetized. Anesthetic agents are pharmacologically active agents that block nerve impulses conduction in sensory and motor nerve fibers when applied in therapeutically effective amounts. Their action is reversible, their use being followed by the complete recovery in nerve function with no evidence of structural damage to nerve fibers or cells. [0003] To be effective, a topical anesthetic should contain sufficient concentration of the active agent to produce an anesthetic effect, it should penetrate intact skin sufficiently to deliver a therapeutic dose, it should exhibit a rapid onset of anesthetic action and have a prolonged anesthetic effect. Potency of anesthetics in clinical situations depend...

AI Technical Summary

Benefits of technology

[0014] It has now been surprisingly found that a topical anesthetic composition comprising a mixture of lidocaine, prilocaine and tetracaine, exhibit a significantly more rapid onset of the anesthetic effect than comparable transdermal anesthetics, such as EMLA cream.

[0017] In another embodiment, lidocaine or its salt on the one side, and prilocaine or its salt on the other side, form an eutectic mixture. As an eutectic mixture, the compositions remain liquid at room temperature and the penetration through the skin is enhanced, giving as a result, a shorter time of effect establishment, a higher efficacy and less adverse effects. Particularly, lidocaine or its salt can be in an amount from about 0.5% to about 5%, w / w, and prilocaine or its salt can be in an amount from about 0.5% to about 5%. More particularly, lidocaine, prilocaine, or their salts are in an amount of about 1.5%, w / w. On the other hand, tetracaine or its salt can be in an amount from about 0.5% to about 8%, w / w, and more particularly, in an amount of about 4%, w / w.

[0020] The composition can comprise at least one spreading agent, which facilitates uniform spread of anesthetic agents. In particular embodiments, the spreading agent is selected from hyalurodinases and / or derivatives of mucopolysaccharidases. They prevent the elevation of extracellular tissue pressure and also prevent focal accumulations of local anesthetic agents, which at high enough levels may cause neurotoxic damage.

[0026] The application of the compositions of the present invention comprises contacting an area of skin with a thin layer of the composition. When an intravenous device is used, the application of the compositions of the present invention will be preferably at its site of insertion. The composition is allowed to act for an appropriate time for the onset of anesthesia. The term “onset of anesthesia” means the time until peak effect on the nerve endings. For the compositions of the present invention, this time is shorter than with other commercial compositions. In a preferred method of using, three consecutive applications may be done: a first application followed by ten minutes of resting to achieve the anesthetic effect; a second application followed by ten minutes more, and a third application followed by five minutes of resting. After these twenty-five minutes in all, the composition can be removed and the surgical operation can be done or the medical device can be inserted. The duration of anesthetic effect for the compositions of the present invention is from about one to about five hours, depending on the subject metabolism. The effect is much more durable and increases in time compared with other available compositions.

Problems solved by technology

Surgical techniques can only be performed after the highly sensitive nerve endings in the skin are anesthetized.

The use of syringe is disadvantageous because the needle itself causes pain on penetration, the volume of anesthetic dissolution can cause stretching at the site (also causing pain), and furthermore preservatives contained in the aqueous dissolution can cause stinging at the wound site.

However, the use of transdermal anesthetics (i.e. through the skin) is often problematic, and fluid and in gel compositions have often proven unsuccessful.

Unfortunately, when administered topically, these formulations are not effectively absorbed transdermally, but only through mucosal surfaces.

Unfortunately, methemoglobinaemia and cyanosis appear to occur more frequently with prilocaine than with other local anesthetics.

Symptoms usually occur when doses of prilocaine hydrochloride exceed about 8 mg per kg body-weight although the very young may be more susceptible.

This fact severely limits the size of the area to be anesthetized.

Enhancement of drug absorption through the skin has been a challenge for researchers for many years.

When applied onto intact skin, currently available topically used anesthetic preparations are generally ineffective or only partially effective.

One approach to the prolongation of anesthesia involves the combination of topical anesthetics with a vasoconstrictor, but also involves considerable adverse side effects.

A major inconvenience of EMLA is that its onset time for anesthesia is relatively long, approximately one hour or more.

This onset time is not very practical for several clinical procedures.

Such delay is a problem for both patients and for medical staff, particularly in the area of pediatrics.

The skin, which has an acidic pH (5 to about 5.5) is sensitive to such a high basic pH and significant skin irritation can occur.

Dermal application of EMLA may cause a transient, local blanching followed by a transient, local redness or erythema.

Another disadvantage of EMLA is that for deep penetrative effect it is necessary that the cream is applied under occlusive dressing.

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