ES2214126B1 - NEW FORMULATION FOR TOPICAL ANESTHESIA, ITS CORRESPONDING KIT MONODOSIS AND ITS APPLICATIONS IN SURGERY. - Google Patents

Abstract

Formulation for topical anesthesia, its corresponding single dose kit and its applications in surgery, characterized in that it is constituted by the following components: - Lidocaine o / w emulsion. - Lidocaine gel. - Adrenaline. - Hyaluronidase. - Emulsion o / w of chlorides. - Stirring rod. The final formulation obtained is a single dose intended to be used entirely at the time of its preparation by mixing its components. The anesthetic formulation has a localized and rapid action; and an application in multiple local surgical interventions, such as: mammoplasty, rhinoplasty, otoplasty, phimosis, surgical laser interventions, gold wire implants, miniliftin, etc.

Description

New formulation for topical anesthesia, its corresponding single dose kit and its applications in surgery.

Technical Field of the Invention

The present invention fits within the Technical field of pharmaceutical products for surgical use and, especially, within the anesthetic products sector.

More specifically the present invention provides a new formulation for topical anesthesia, based on lidocaine with application in a wide variety of interventions Surgical

State of the art prior to the invention

Local anesthetics act by inhibiting transiently painful sensitivity, when they are put on direct or indirect contact with a nerve trunk or with its endings The point of action of these drugs are nerves afferent and sensitive terminal organs.

When applied locally, anesthetics premises block nerve conduction paralyzing the fibers sensitive without prior stimulation and reversibly, so that when the drug is absorbed and eliminated, the nerve recovers the Function in its entirety.

Lidocaine, in its hydrochloride form, is a Anesthetic drug widely known and used. It is defined in the European, French, Italian, Swiss pharmacopoeias, British and American

More specifically, lidocaine hydrochloride It is a local anesthetic type amide widely used topically as a mucosal anesthetic and also in infiltration anesthesia and in others.

Usually, local type anesthetics Amide (for example, lidocaine, prilocaine, bupicavain) are used more profusely than those of the ester type (for example, benzocaine or procaine) because they cause less hypersensitivity.

Lidocaine has a weak ability to be absorbed through intact skin, however it is susceptible to be absorbed in high proportions through the mucous membranes or the damaged or injured skin. This is the factor that you have to have very much in account, because unwanted excessive absorption per application topical could cause general adverse effects, such as toxicity to the central nervous system (agitation, euphoria, nervous depression, etc.) and about the cardiovascular system (hypotension, bradycardia, etc.).

In this context, the present invention provides a new anesthetic formulation for topical use to Lidocaine base, where this product is introduced into the formulation in a certain form and concentration, along with other components, resulting in a formulation with important advantages as a local topical anesthetic for surgical interventions.

Detailed description of the invention

The present invention, as indicated in its  statement refers to a new formulation for anesthesia topical, to its corresponding single dose kit and its applications in Various surgical interventions.

The formulation of the invention is characterized because it is constituted by:

-

Lidocaine o / w emulsion

-

Gel lidocaine

-

Adrenalin

-

Hyaluronidase

-

Emulsion o / w calcium chloride, potassium, magnesium and sodium.

The emulsion o / w (oil in water) of lidocaine a use in the present invention is essentially constituted by an o / w base, lidocaine HCL, preservative and water. A illustrative composition of the composition corresponding to said Emulsion is as follows:

Base o / w 400 g Lidocaine HCL 2% Preservative 0.1% Water csp 1000 g

As an oily base, any base can be used  Pharmaceutically acceptable oil (example 1011 Deex).

As a preservative, a preservative can be used  Pharmaceutically acceptable selected from: BHT, Kathon.

The water to be used is a water that meets the specifications required for pharmaceutical products intended To topical use.

The lidocaine HCL to be used must have obviously pharmaceutical quality and is a commercially product affordable.

To obtain the required emulsion and a Once the components are weighed, proceed as follows:

1) introduce the oil base in a water bath 70 ° C approximately until melting;

2) also introduce the aqueous phase in the bath to the same temperature approximately and incorporate the lidocaine and the preservative;

3) transfer both phases to the homogenizer, pouring the aqueous phase over the fatty phase and stir until emulsion formation, a surfactant can be incorporated to confer stability to the mixture;

4) allow to cool the emulsion thus obtained until about 40 ° C and pack it.

The lidocaine gel to be used herein invention consists essentially of lidocaine, sodium carboxymethyl cellulose, preservative and water. A composition illustrative of the composition corresponding to said gel is the next:

Lidocaine 20 g Carboxymethyl cellulose sodium 2% Preservative 0.1% Water 960 g

As a preservative, any of those mentioned above.

The water to be used must comply with the specifications required for pharmaceutical products.

The sodium carboxymethyl cellulose to be used will be Pure and pharmaceutical quality.

To obtain the referred gel and once Heavy components are proceeded as follows:

1) dissolve the lidocaine and preservative in the Water,

2) disperse sodium carboxymethyl cellulose in a portion of the above solution and homogenize well;

3) incorporate the rest of the solution of (1) until the desired volume is completed.

The temperature at which the process is carried out is from 60ºC to the water bath.

During the gel formation process you have to be careful not to incorporate air, and otherwise You may lose transparency. Mixing can be carried out manually, but the process is accelerated if you work with a turboagitator which also helps the inclusion of air in the Mix be minimal.

Hyaluronidase is used in the form of pharmaceutical grade powder composition, being preferably the proportion of hyaluronidase in said composition on the order of 10-4 p / p.

Adrenaline is used as a solution 0.1% liquid, also of pharmaceutical quality.

The emulsion o / w of chlorides, these were used because they don't cause any problems; what would not happen if we use gluconates that would alter the acid molecules hyaluronic and anesthesia would pass systemically, or when using sulfides because SH groups would form giving problems of toxicity.

The emulsion o / w of chlorides to be used in the The present invention consists essentially of glyceryl monostearate, isopropyl myristate, liquid petrolatum, dimethicone, water, preservative and calcium chloride, potassium, magnesium and sodium in equal parts. An illustrative composition of the composition corresponding to said emulsion is the next:

TO.- Glyceryl monostearate 14% Myristrate of isopropyl 8% Vaseline liquid 4% Dimethicone 7% B.- Water demineralized csp 100 C.- Preservative 0.1% D.- Chloride calcic 10% Chloride magnesium 10% Chloride sodium 10% Chloride potassium 10%

As a preservative, a preservative can be used  Pharmaceutically acceptable as Kathon.

To obtain the aforementioned emulsion and a Once the components are weighed, proceed as follows:

1) Heat at 70º-75ºC in a water bath and by separate (A) and (B).

2) Dissolve (C) in (B) once it is melted and Then add the preservative.

3) Pour the phase obtained in point (2) on (A) and work the emulsion

The anesthetic formulation of the invention is It is presented as a single dose kit for topical anesthesia.

The kit consists of the following elements:

- a first container containing the emulsion o / w of lidocaine;

- a second container containing the gel lidocaine;

- a third container containing the composition  hyaluronidase powder;

- a fourth container containing the emulsion o / w of calcium, potassium, magnesium and sodium chlorides;

- a vial containing the solution of adrenalin; Y

- a sterile mixing rod.

All elements of the kit must meet the aseptic conditions, sterility and pharmaceutical quality required for a pharmaceutical product intended for anesthetic use topical

The proportions of each component in each kit item must conform to the proportions of the general formulation given above, taking into account that the Final formulation obtained is a single dose intended to be used entirely at the time of preparation by mixing of its components.

For the use of the kit of the invention, produces asepsis of the area to be treated, mixes uniformly kit components and the mixture is applied on the area to be treated. The anesthetic action is rapid and the duration of the effect is about two hours.

The formulation of the invention achieves prevent lidocaine from being absorbed into the venous circulation which would result in an unwanted systemic absorption of drug.

The presence of adrenaline in the mixture, contributes to the effect indicated in the previous paragraph because it produces  localized vasoconstriction while prolonging the duration of anesthetic effect

With the presence of calcium, potassium ions,  magnesium and sodium in the mixture, we keep the pressure intact osmotic facilitating the diffusion of anesthesia, getting the anesthetic effect in less time and on the other hand we ensure that the anesthetic effect occurs very safely in the area planned without being able to pass systemically.

The multiple experiences carried out by the applicant have allowed to show that by employing the formulation of the invention diffuses carbonic anhydride in the peripheral nerves lowering the intraneural pH, which favors ion treatment reinforcing the action of hyaluronidase, especially in the presence of water. This produces a circuit closed through which the anesthetic formulation circulates only in the area of the epidermis, without reaching the dermis.

On the other hand, hyaluronidase is an enzyme that has a great capacity to immobilize large amounts of Water. Specifically, it is a widely distributed endoglucosidase which separates hexosamidine bonds, with action on the acid Hyaluronic and Chondroitin Sulfate.

In the experimental interventions performed by the applicant with the formulation of the invention has observed, additionally, that it accelerates the regeneration of the tissues intervened in relation to other anesthetics conventional. This is explained on the basis that the immobilization product anesthetic causes adrenaline to stimulate the production of the enzyme adenylate cyclase, which concentrates on the inner surface of cell membranes, leading to an increased production of ATP that acts as a source of energy for cell regeneration and therefore of the tissues of the area intervened

The anesthetic formulation of the invention has application in multiple surgical interventions of character local, among which the following may be mentioned: mammoplasty, rhinoplasty, otoplasty, gold wire implants and others implants, phimosis and other penile surgeries, blepharoplasty, miniliftin, surgical laser interventions, etc.

Embodiments of the invention

The present invention is further illustrated. by the following Examples, which are not intended to be limiting its scope, delimited exclusively by the note attached claim.

Example 1

An individual single dose kit was prepared that understood:

one)

Lidocaine emulsion o / w 2%, csp 10 g

2)

Gel of 2% lidocaine, csp 10 g

3)

Hyaluronidase powder (1 mg), csp 10 g

4)

Adrenaline 1 ampoule of 1 ml (0.1% solution), cps 10

5)

Calcium Chloride Emulsion, Potassium,  magnesium and sodium or 10% w / w, in equal parts.

Each of the above products was arranged In a separate container.

Example 2

An individual single dose kit was prepared that understood:

one)

65% lidocaine o / w emulsion, csp 10 g

2)

Gel of 65% lidocaine, csp 10 g

3)

Hyaluronidase powder (1 mg), csp 10 g

4)

Adrenaline 1 ampoule of 1 ml (0.1% solution), csp 10

5)

Calcium Chloride Emulsion, Potassium,  magnesium and sodium or 10% w / w, partly the same,

Each of the above products arranged in An independent container.

Claims (19)

1. Formulation for topical anesthesia, characterized in that it consists of the following components:

-

Lidocaine o / w emulsion

-

Gel lidocaine

-

Adrenalin

-

Hyaluronidase

-

Emulsion o / w calcium chloride, potassium, magnesium and sodium.

2. Formulation according to claim 1, characterized in that the concentration of lidocaine in the emulsion o / w is 65% by weight. 3. Formulation according to claim 1, characterized in that the concentration of lidocaine in the gel is 65% by weight. 4. Formulation according to claim 1, characterized in that the adrenaline is used as a 0.1% liquid solution. 5. Formulation according to claim 1, characterized in that the hyaluronidase is used in the form of a powder composition at a concentration of 10-4 w / w. 6. Formulation according to claim 1, characterized in that the concentration of calcium, potassium, magnesium and sodium chlorides in the o / w emulsion is 10% in equal parts. 7. Single dose single kit for the topical anesthesia formulation of claim 1, characterized in that it comprises the following elements: - a first container containing the emulsion o / w of lidocaine; - a second container containing the gel lidocaine; - a third container containing the composition  hyaluronidase powder; - a fourth container containing the emulsion o / w of calcium, potassium, magnesium and sodium chlorides; - a vial containing the powder solution of hyaluronidase; Y - a sterile mixing rod. 8. Kit according to claim 6, characterized in that it comprises the following components in separate containers:

one)

65% lidocaine o / w emulsion, csp 10 g

2)

Gel of 65% lidocaine, csp 10 g

3)

Hyaluronidase powder (1 mg), csp 10 g

4)

Adrenaline 1 ampoule of 1 ml (0.1% solution), cps 10

5)

Calcium Chloride Emulsion, Potassium,  magnesium and sodium or 10% w / w in equal parts.

9. Application of the formulation of the claim 1, in the manufacture of a local topical anesthetic for surgical interventions. 10. Application of the formulation of the claim 1, in the manufacture of an individual single dose kit,  according to claims 7 and 8 above, for interventions Surgical 11. Application according to claims 9 and 10, characterized in that the surgical intervention is a mammoplasty. 12. Application according to claims 9 and 10, characterized in that the surgical intervention is a rhinoplasty. 13. Application according to claims 9 and 10. characterized in that the surgical intervention is an otoplasty. 14. Application according to claims 9 and 10, characterized in that the surgical intervention is an implant, especially an implant of gold wires. 15. Application according to claims 9 and 10, characterized in that the surgical intervention is a phimosis. 16. Application according to claims 9 and 10, characterized in that the surgical intervention is penile surgery. 17. Application according to claims 9 and 10, characterized in that the surgical intervention is a blepharoplasty. 18. Application according to claims 9 and 10, characterized in that the surgical intervention is a miniliftin. 19. Application according to claims 9 and 10, characterized in that the surgical intervention is a surgical laser surgery.