Novel alkalized solid-liquid two-state skin quick-anaesthesia nano-emulsion and preparation method thereof

Abstract

The invention relates to a novel alkalized liquid-state and solid-state rapid skin anesthesia nanometer emulsion for skin external application and a preparation method thereof. The inventive nanometer emulsion mainly comprises three systems: the first system is a skin anesthesia effective ingredient system, the second system is a nanometer emulsion composition system, and the third system is a nanometer emulsion excipient protective system. The three systems can be used for preparing a liquid-state and solid-state rapid anesthesia nanometer emulsion for skin external anesthesia. The inventive nanometer emulsion compounds three anesthetics with respective characteristics and contains menthol, so that the formula is more reasonable and the effect is more distinct, wherein tetracaine has strong transdermal capacity, rapid action and strong local anesthetic action, the anesthetic action of chloroprocaine is 4-6 times stronger than procaine and 2-3 times stronger than lidocaine, and the chloroprocaine has low toxicity, high penetration capacity, quick action and long-lasting anesthetic action.

Description

technical field [0001] The invention relates to a novel alkalized liquid and solid epidermal rapid anesthesia nanoemulsion for external use and a preparation method thereof, and the technical field belongs to pharmaceutical preparations and medical cosmetic products and technologies. Ornamentation (including eyebrow, lip, eyeliner, tattoo), freckles, black hemorrhoid removal, grinding, epidermal anesthesia and analgesia before eyebrow washing, can also be directly used in plastic surgery, dermatology and medical cosmetology Epidermal anesthesia and analgesia for surgery. Background technique [0002] Background technology of local anesthetics: Local anesthesia methods and routes of administration at home and abroad are mostly performed by subcutaneous injection of anesthesia injections, skin smearing of anesthesia external preparations, and surface spraying of anesthesia sprays. The most commonly used local anesthetics are: ① Procaine: the earliest synthetic ester local ane...

AI Technical Summary

Problems solved by technology

At present, clinically, various puncture examinations, skin venereal diseases (such as biopsy, electrocautery, curettage, laser, liquid nitrogen freezing and chemical peeling, etc.), plastic surgery and laser cosmetology and other invasive medical methods are caused. Superficial traumatic pain of the skin, which has been given sufficient attention but technically incapable of action

In order to reduce the pain caused by plastic surgery or medical aesthetic treatment, superficial skin surgery and puncture, subcutaneous local injection of anesthesia drug infiltration anesthesia is still generally used, but the pain and psychological fear caused by injection often lead to poor patient compliance. In particular, the fear and anxiety of children and women are becoming more and more obvious and prominent, and the injection of some treatment parts is difficult and not very convenient, especially the skin anesthetics currently used for external application, including some new ones. The developed anesthesia sprays, tinctures, emulsions, creams, ointments, gels, etc. seem to have solved the tediousness and pain of injection anesthesia, and are indeed simple and convenient to use. The onset time of anesthesia is usually more than 1 hour, and the anesthesia intensity and anesthesia maintenance time are very limited. Even if some sealing measures can improve some anesthesia effects, the effect is not very obvious, which seriously affects people's confidence and patience in use

[0006] As mentioned earlier, currently the most widely used skin topical anesthetic in the world is Enna cream (EMLA) developed and produced by AstraZeneca, Sweden, which is compound lidocaine cream, but the shortcoming of this preparation is the onset time It is relatively slow, and it is a topical anesthetic, which can only be used for minor surgical anesthesia, and it cannot achieve pain relief for such as dermabrasion and plastic surgery.

Moreover, prilocaine in Enna cream can increase blood methaemoglobin at high doses, which may affect tissue oxygenation and may cause methaemoglobinemia and contact allergy. Therefore, infants under 3 months old, congenital Patients with sexual and idiopathic methemoglobinemia should not use EMLA cream or patch, and because it has a constricting effect on blood vessels, the skin may have whitening and other adverse reactions after external use. The clinical use of EMLA is greatly limited. , and so far EMLA has withdrawn from the Chinese market

In addition, there are gels, tinctures, creams and other skin local anesthesia external preparations of anesthetics such as lidocaine and tetracaine, all of which have slow onset time (more than 1h) and insufficient percutaneous penetration effects; New preparations such as liposomes with the characteristics of non-toxicity, no side effects, and no immunity, or thermodynamically stable and biodegradable cubic liquid crystals, etc., also have problems such as thermodynamic instability, large particle dispersion, and unsatisfactory transdermal rates. It is easy to oxidize and hydrolyze in the liquid state, and the factors such as too long equilibration time are not ideal transdermal drug delivery carriers

Although lidocaine can be used for multiple forms of local anesthesia, it also has many disadvantages or deficiencies in application, although the local anesthesia glue containing concentration of 60% lidocaine externally applied skin as developed by Japan Lederle Company is easy to use. , has no side effects, and can significantly relieve pain, but it needs to be pasted for more than 2 hours to have a significant anesthetic effect, and the effect of the tape is different at different room temperatures or different skin temperatures, and the effects of young and old people are also different. Practical application is limited

The present inventor has also prepared it into a 5% nanoemulsion anesthesia preparation for external use on the skin, but found that its anesthesia has a slow onset and a short maintenance time, and has obvious skin irritation and skin cuticle dissolution and epidermal cell damage.