DESCRIPTION Field of the Invention

The present invention relates to the topical composition comprising Calendula officinalis, Hypericum perforatum and a local anesthetic; that can be used for the treatment and the cure of external lesions, which have wound healing, antiseptic, anti-bacterial, anti-inflammatory and pain relieving properties.

Background of the Invention

Calendula or marigold has been used since the time of the Greeks as a skin balm and antiinflammatory. Calendula (Gold-Bloom ) marigold, is a genus of about 12-20 species annual or perennial herbaceous plants in the daisy family Asteraceae, native to an area from Macaronesia east through the Mediterranean to Iran. It is commonly used for skin conditions including minor abrasions and burns, conjunctivitis, aphthous stomatitis, pharyngitis, hemorrhoids, diaper rashes and ulcers. In addition, marigold has been shown to increase blood circulation and to aid in healing blood stagnation bruises. Experimental in vivo research suggests that marigold gently stimulates the immune system and promotes lymphatic drainage as well as reducing inflammation and pain.

Calendula ointment Unguentum "Calendula" which contains tincture of calendula (on 70% spirit 1:10)-20 g, vaseline-90 g: [Mashkovskij M. V. "Medicinal Means", Moscow, "Medicine" 1986, vol. 2, p. 2.424] (US 5997876 CI.1, Ln.7-15).

St. John's wort or Hypericum has been used to treat many ailments, including cuts, grazes, bruises, minor bums, sciatica, injured nerves, inflammations, ulcers, poisonous reptile bites, kidney and lung ailments, allergic reactions, anxiety and depression. In addition, St. John's wort is also a good source of antioxidants: with 11.7% of its content being bioflavonoids such as rutin, hyperoside, quercetin and quercrtrin, St. John's wort is one of the most concentrated herb sources of antioxidants.

There is also known "Ointment Kolkhuri", which contains St.John's-wort, the oak bark, haw- thorn, yarrow, yellow melilot, horse-chestnut 0.06-0.065 in equal quantity, nettle 0.10-0.11 , gum- tree extract 0.02, belladonna extract 0.02, vaseline-the rest; [GE 13, Oarsania, V. 15.05.94]. (US 5997876 CI.1, Ln.17-35). This ointment is used as analgetic and antiinflammatory means and is less effective for healing the wounds and burns, as haw-thorn and belladonna arc not characterized by antiinflammatory and regeneration stimulating effect.

Local anaesthetic is a type of medication used to numb areas of the body. Local anaesthetic causes a complete loss of pain sensation to a specific area of body without losing consciousness. It works by blocking the nerves from the affected part of body so that signals can't reach the brain. It only takes a few minutes to lose feeling in the area where local anaesthetic is given. Medical uses are acute pain, chronic pain, surgery, podiatry, dentistry, painless venipuncture and some endoscopic procedures such as bronchoscopy (visualization of the lower airways) or cystoscopy (visualization of the inner surface of the bladder). Topical anaesthesia contains local anaesthetic and is available over the counter from pharmacists in the form of creams, sprays and ointments.

W01997/42963 describes an ointment used in the treatment of burnings and skin diseases that includes some types of plants such as Chelidonium majus, Plantago major, Matricaria chamomilla, Achillea millefolium, Calendula officinalis, Hypericum perforatum, Eucalyptus globus, Oleum olivarum and yellow beewax of Cera flava.

WO2005/063266 describes a composition for topical use that uses the extract of Calendula officinalis and Hypericum perforatum that they include peptides of low molecular weight and free aminoacids. Described composition in this document is destined for the treatment of psoriasis. Despite the lots of known therapeutical compositions, the problems in treating wound, still exist since these drugs available are not sufficient to improve conditions and alleviate symptoms like epithelial damage, stinging, inflamation. There is a need for improvement of the known drugs due to fast and complete healing requisites.

Summary of the Invention

The present invention relates to topical application of a safe pharmaceutical composition comprising Calendula officinalis, Hypericum perforatum and a local anesthetic; that can be used for the treatment and the cure of external lesions, which have wound healing, antiseptic, antibacterial, anti-inflammatory and pain relieving properties.

Disclosure of the Invention

The present invention provides a topical pharmaceutical composition comprising Calendula officinalis, Hypericum perforatum and a local anesthetic. In one embodiment, topical pharmaceutical composition of present invention contains Calendula officinalis which can be used in the form of essential oil or alcoholic or non-alcoholic extract thereof.

In one embodiment, topical pharmaceutical composition of present invention contains Hypericum perforatum which can be used in the form of essential oil or alcoholic or nonalcoholic extract thereof.

Local anesthetics belong to one of two classes: aminoamide and aminoester local anesthetics. Ester class local anesthetics are prone to producing allergic reactions, which may necessitate the use of an amide class.

In one embodiment, in the present invention, local anesthetics can be selected from the group consisting of Benzocaine, Chloroprocaine, Cyclomethycaine, Dimethocaine, Piperocaine, Propoxycaine, Procaine, Proparacaine, Tetracaine, Articaine, Bupivacaine, Cinchocaine, Etidocaine, Levobupivacaine, Lidocaine, Mepivacaine, Prilocaine, Ropivacaine, Trimecaine and pharmaceutical acceptable salts thereof.

In the preferred embodiment, in the present invention, local anesthetic is selected from amide class due to safety reasons. More preferably, local anesthetic is lidocain in the form of base or acid addition salts thereof.

Lidocaine is a well known and commercially available local anesthetic of amide class. It is widely used to treat pain and itching associated with insect bites, sunburn, contact dermatitis, and in connection with anal-rectal conditions such as hemorrhoids, fissures and infections. In one embodiment of present invention, the topical anesthetic material is disposed in a carrier which is a cream, lotion or gel, and in many instances, liposomal structures are particularly favored carriers. As is known in the art, liposomal structures comprise vesicles having walls formed from a phospholipid or similar material.

In certain embodiments of the present invention, topical pharmaceutical composition is in the form of external preparations, such as ointments, creams, gels, lotions, liquids, sprays, cataplasmas, tapes, preferably in the form of gel.

In certain embodiments of the present invention, in addition to the herbal active ingredients described above, topical pharmaceutical composition optionally further contains one or more physiologically acceptable carriers, gelling agents, preservatives, emulsifiers, emollients, humectants, dispersants.

In certain embodiments of the present invention, topical pharmaceutical composition comprises a pharmaceutically acceptable carrier selected from the group consisting of water, alcohol, almond oil, lanolin, ascorbyl palmitate, beeswax, benzyl alcohol, capryl/capramidopropyl betaine, carboxymethylcellulose sodium, castor oil, cetyl alcohol, cocoa butter, xanthan gum corn oil, hydrogenated vegetable oil, cottonseed oil, glycerin, glyceryl oleate, glyceryl stearate, hydroxyethylcellulose; kaolin, lactose, light mineral oil, microcrystalline wax, olive oil, palm oil, paraffin, PEG 12 diiaurate, Peruvian balsam, petrolatum, polyethylene gycol 300, polyethylene wax, propylene glycol, sorbitan sesquioleate, soybean oil, sucrose, starch, stearyl alcohol, wax, white petrolatum and mixtures thereof.

In certain embodiments of the present invention, topical pharmaceutical composition comprises a pharmaceutically acceptable gelling agent can be selected from the group consisting of acacia, alginic acid, bentonite, carbopols, carbomer 940, carbomer 941, gelatin, carbomer copolymer, aluminum monostearat, dextrin, magnesium aluminum silicate, silicon dioxide, sodium alginate, triethanolamine, polyvinyl alcohol, pectin, methylcellulose, hydroxypropyl cellulose, aqueous thickening agents such as neutral, anioniocationic polymers and mixtures thereof.

In certain embodiments of the present invention, topical pharmaceutical composition comprises an emulsifier can be selected from the group consisting of -20, laureth-3, glyceryl stearate, polyethylene glycol, macrogol cetostearyl ether, stearic acid, stearyl alcohol, polysorbate 60, Irish moss, Tween 80, sorbitol monostearate.glycol esters, fatty acids, fatty alcohols, fatty acid glycol esters, fatty esters, fatty ethers, esters of glycerin, esters of propylene glycol, fatty acid esters of polyethylene glycol, fatty acid esters of polypropylene glycol, esters of sorbitol, esters of sorbitan anhydrides, carboxylic acid copolymers, esters and ethers of glucose, ethoxylated ethers, ethoxylated alcohols, alkyl phosphates, polyoxyethylene fatty ether phosphates, fatty acid amides, acyl lactylates, soaps, polyethylene glycol 20 sorbitan monolaurate (polysorbate 20) , polyethylene glycol 5 soya sterol, steareth-2, steareth-20, steareth-21, ceteareth-20, PPG- 2 methyl glucose ether distearate, ceteth-10, polysorbate 80, cetyl phosphate, potassium cetyl phosphate, diethanol amine cetyl phosphate, polysorbate 60, glyceryl stearate, PEG-100 stearate, tragacanth gum, 10-30 alkyl acrylate crosspolymers and mixtures thereof.

In certain embodiments of the present invention, topical pharmaceutical composition comprises an emollient can be selected from the group consisting of liquid vaseline, paraffinum liquidum, petrolatum, proplylene glycol, fatty acid esters, mineral oil including dimethicone, waxes including white wax, spermacetic wax, squalene, cetearyl alcohol, cetostearyl alcohol, stearyl alcohol, 2-Octyldodecanol, mineral oil USP, light mineral oil NF, liquid paraffin BP, light liquid paraffin BP.candellilla wax, sweet almond oil, apricot oil, emu oil, argan oil, glycerin, coconut oil, grape seed oil, honey, lanolin and mixtures thereof. In certain embodiments of the present invention, topical pharmaceutical composition comprises a preservative, particularly a preservative selected from the list of potassium sorbate, polyhexanide, paraben (methyl, propyl, butyl, isobutyl), phenoxyethanol, propylene glycol, benzoic acid and benzyl alcohol, particularly potassium sorbate. In particular embodiment, the concentration of the preservative is between about 0.005% and about 0.5%, particularly at about 0.1%, at about 0.2%.

In one embodiment of the present invention, topical pharmaceutical composition may not contain any paraben.

In preferred embodiment, the preservative is potassium sorbate. In particular embodiment, potassium sorbate is the sole preservative present in the composition.

In certain embodiments of the present invention, topical pharmaceutical composition comprises humectant selected from the group consisting of sorbitol, ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, glycerol, mannitol, xylitol, maltitol, glycerol ethylene oxide (EO), propylene oxide (PO) adducts, and combinations thereof.

The herbal topical composition of the invention preferably are made in a gel base. Preferably, gel base comprises water, glycerine, Sepineo P600 (acetalization product between glucose and 12-hydroxystearyl alcohol - Seppic) and potassium sorbate.

Also unexpectedly, it has been found that the activity is highly prolonged with less side effects particularly when compared to popular or leading commercially available preparations.

Sample gel formulation is below:

Example 1.