HK1027505B - Analgesic combination - Google Patents

Description

Analgesic mixture

The invention relates to a pharmaceutical product for oral administration comprising a fixed mixture of at least one fast acting local onset analgesic and at least one long acting systemic onset analgesic.

Fast acting, local onset analgesics which may be used, for example, in the form of sprays or lozenges are known. This type of anesthetic begins to work in less than one minute, but has a short duration of action, often requiring frequent administration, which is detrimental to safety and patient compliance.

An example of a particularly interesting local-acting analgesic is benzocaine. They inhibit the generation and conduction of (neural) impulses by blocking sodium flow within the nerve.

Systemically acting analgesics such as the NSAIDs class, in particular acetylsalicylic acid (ASA), represent another possibility for pain relief. These analgesics decrease nociceptor sensitivity, and the relief of pain can be explained by the inhibition of synthetic prostaglandins. Most of these systemically acting analgesics do not achieve maximum activity until after about 1-2 hours.

It is an object of the present invention to meet a long-standing need of providing an orally administered article which combines immediate and sustained action in a simple and reliable manner.

The active substance (element a) for local onset of pain is such that it starts to act significantly within at most 10 minutes, preferably 4 minutes, more preferably 1 minute and most preferably 30 seconds.

The local acting analgesic (element a of the cocktail) is conveniently used in an amount of 0.5-100, preferably 1-60, more preferably 2-30mg per individual administration form.

The compositions of the invention may contain one or more local anaesthetics as element A, for example 1, 2 or 3. Mixtures with only one element A compound are of particular interest.

The active substances of the element a are known per se. Particularly suitable examples which may be mentioned are ester-type local anaesthetics, such as benzocaine, tetracaine, amethocaine, bupivacaine, butoxycaine (butoxycaine), butyl aminobenzoate, chloroprocaine, chloromocaine (chloromecaine), cyclomethiocaine, amiben-butyl, mepivacaine, oxybuprocaine, procaine, propiocaine, proparacaine, tricaine and the like. Also described are local anesthetics of the anilide type such as lidocaine, bupivacaine, butanacaine, ticarcine, cinchocaine, chloroucaine, etidocaine, mepivacaine, oxybivacaine, prilocaine, ropivacaine, ethyl p-piperidineacetyl-aminobenzoate, tolicaine, trimecaine, valdocaine and the like.

Other local anesthetics can also be used, such as pramoxine or essential oils like menthol or eucalyptus oil.

Non-steroidal anti-inflammatory drugs (NSAIDs) such as phenylacetic acid derivatives such as aceclofenac, alclofenac, bromofenac, diclofenac, fenclofenac, and the like; arylacetic acid derivatives such as acemetacin, amfenac sodium, benzydac, meglumine, oxametacin and the like; p-aminophenol derivatives such as acetanilide and the like; propionic acid derivatives such as alminoprofen, ibuprofen, ketoprofen, flurbiprofen, naproxen, oxaprozin; salicylic acid derivatives such as aspirin (ASA), the aluminum and other salts of ASA, diflunisal, etosalate, fossalate, phenyl salicylate, salsalate, salicylamide, and the like; pyrazolone derivatives such as aminopyrine, analgin, etc.; oxycam derivatives such as droxyxicam, isoxicam, piroxicam, and the like; phenylbutazone derivatives such as Yangtongan, calcium phenylpropionate-phenyl hydrazine, oxybutyzone, etc.; indole pyranoacetic acid derivatives (pyranoindolacetic acid) such as ethidolic acid and the like; anthranilic acid derivatives such as glafenin, meclofenamate sodium, mefenamic acid, flumorph, and the like; indole derivatives such as indomethacin, etc.; acetaminophen and acetaminophen derivatives and other NSAIDs such as anisic acid, benproperitone, benzydamine hydrochloride, sodium isobutyrylbutyrate, lorcinozine, cinnamyl amine nicotinate, chlorhydroxyfenacin, bipyramid, diproprione, ethacrylamide, cumazolone, flupirtine maleate, fenpropimoximate, indoprofen, propiophenone, meloxicam, phenothiazine acetic acid, metifenazone, nifenizone, niflumic acid, mimesulide, chlorofluoropyrazole acid, pranoprofen, propaquizal, phenothiazinepropionic acid, raminolone, and the like.

The amount of the systemically effective analgesic in element B of the present invention is 5 to 1500, preferably 8 to 1000, more preferably 10 to 800mg per dose.

The preferred topical analgesics used as element A are fast acting and have an optimal duration of action of 0.5 to 120, preferably 2 to 60, more preferably 5 to 30 minutes. The preferred use of component B as a systemic analgesic should start to act distinctly after 15 minutes and last for up to 24 hours, preferably after 20 minutes and last for up to 12 hours, particularly preferably up to 8 hours.

In one embodiment of the article of the invention, the elements a and B are chosen such that the fixing agent has an action time of 2 minutes to 12 hours.

Of particular interest is a composition according to the invention which contains as element A an ester-type local anaesthetic, in particular benzocaine, and as element B a propionic acid derivative or a salicylic acid derivative, in particular ASA.

Preferred systemic analgesics have a duration of action of at least 3 hours.

The compositions of the invention are particularly suitable for treating inflammatory and/or painful conditions of the oropharynx, in particular, for example, pharyngitis, laryngitis, tonsillitis, stomatitis, gingivitis of various etiologies. The mixture product of the present invention can be conveniently administered orally.

The mixture can be used in conventional formulations, where the local anaesthetic should be released first and the analgesic acting systemically optionally also in storage form.

The invention also relates to a method for producing a pharmaceutical preparation, characterized in that a fixed mixture of an active substance of the element A and an active substance of the element B, together with customary auxiliary substances and carriers and optionally other compatible active substances, is converted into a suitable administration form such that the locally effective analgesic is released first.

Examples of these preparations are described below: tablet with a coating, coated lozenge, chewing gum, hard caramel with a liquid, semi-solid or solid core. They can be produced by a general method using conventional auxiliary substances.

Examples

Example 1

The following tablet compositions are described by way of example:

ASA core tablet:

500mg of ASA was flavoured with 30mg ascorbic acid, 75mg sucrose, 47mg microcrystalline cellulose, 2mg saccharin (550X) and 6ml orange juice to give a tablet weighing 660mg total. The tablet cores were uniformly coated with a coating syrup containing benzocaine, coating a total of about 5mg benzocaine and 602mg coating syrup. The tablets indicated significant analgesic effect for only two minutes after administration and a duration of more than 3 hours.

Example 2

Nucleated tablets containing 300mg naproxen were coated with a coating syrup containing 500mg lidocaine in a manner similar to example 1. This composition preparation showed onset of action after 2 minutes and a duration of more than 6 hours.

Claims (4)

1. A pharmaceutical product for oral administration comprising at least one fast acting local acting analgesic as element a and at least one long acting systemic acting analgesic as an immobilization agent of element B, formulated such that the local acting analgesic is released first.

2. Article according to claim 1, characterized in that the active substance used as element a exhibits an optimum action time of between 0.5 and 120 minutes and the active substance used as element B acts between 15 minutes and 24 hours.

3. Article according to claim 1, characterized in that the elements a and B are selected such that the fixing agent has an action time of 2 minutes to 12 hours.

4. A process for the preparation of a preparation according to claim 1, characterized in that an immobilized mixture of an active substance of the element a and an active substance of the element B with conventional auxiliary substances and carriers and optionally other compatible active substances is converted into a suitable administration form such that the locally acting analgesic is released first.