WO1999038517A1

WO1999038517A1 - Compositions for oral treatment of warts

Info

Publication number: WO1999038517A1
Application number: PCT/FI1999/000061
Authority: WO
Inventors: Kari Honkanen
Original assignee: BENE PHARMA Oy
Current assignee: BENE PHARMA Oy
Priority date: 1998-01-30
Filing date: 1999-01-29
Publication date: 1999-08-05
Anticipated expiration: 2000-07-30
Also published as: AU2057299A; FI980216A0

Abstract

The present invention is related to the use of pharmaceutically acceptable magnesium salts, especially magnesium sulphate salts for the manufacture of medically active compositions for treatment of warts by oral administration. In addition to the active ingredient the medicine comprises one or more pharmaceutically acceptable, functionally inert, solid or liquid excipients. The preferred liquid excipient is an aqueous, buffered or non-buffered solution, optionally comprising pharmaceutically acceptable, physiologically inert polyols, such as sugar alcohols and/or glycerol. In the most preferred embodiment of the invention the magnesium ions are provided in the form of tablets especially effervescent tablets, which upon dissolving provide tasty sparkling drinks.

Description

COMPOSITIONS FOR ORAL TREATMENT OF WARTS

The Technical Field

The present invention is related to the use of pharmaceutically acceptable organic and/or inorganic magnesium salts for manufacturing of medically active, orally administrable compositions for treatment of warts.

The Background of the invention

Warts (Verruca vulgaris) are tumour-like changes in the skin. They are believed to be caused by virus infection especially Papilloma virus. They usually present on the feet and hands of the patient. School children are especially vulnerable. They often catch the infection in connection with gymnastics and sport in gymnasia, public swimming pools and baths.

Warts are generally treated by applying directly on the warts different subcutaneous compositions. Preparations, comprising magnesium, but also sodium, calcium and potassium have been demonstrated to be effective in treatment of acne, seborrheic dermatitis as well as other skin diseases (EP 656 270). Even if treatment of skin is mentioned, treatment of warts is not specifically mentioned and the composition is used subcutaneously in the form of gels, salves, shampoos or liquid or solid soaps in contrast to the present invention, which comprises liquids or tablets for treating warts by oral administration of the medicine.

The patent application DE 19541735 discloses the use of hydrothermal rock deposits containing, magnesium in a combination with several other substances in health care. In addition to the subcutaneous use, as bath salts, soaps, lotions, massage oils, sun creams, etc. , it is also suggested that the rock deposit could be used as enteral compositions or intravenously in form of drinks, tinctures, elixirs, homeopathic materials, globules, infusions, tablets, etc. , for treating such condition as skin problems, wans, excema, orange-peel skin, psoriasis, acne, etc. There is however no indication that the magnesium ion could be the active ingredient in said composition.

Magnesium-containing products have been used in therapy as antacids, laxative and purgative preparations, as metabolic regulators, anticonvulsants and sedatives (CA 111 : 201228v, 1989). However, even if said products contain magnesium, it is not always the magnesium ions, which are responsible for the therapeutic function. In some cases. it is the anion, e.g. the sulphate anion in magnesium sulphate, which is considered to be the active ingredient in the medical application.

Magnesium ions, especially magnesium pyrophosphate, in combination with B6-vitamins have been suggested for treatment and prophylaxis of neoplastic and autoimmune diseases (WO 95/31991). Using up to 368 mg magnesium pyrophosphate per kg body weight daily, recovery in form of lesion disappearance and/or reduction to negative values of the activity index of the disease was obtained in time intervals of approximately three to twelve months. In said patent there is no indication that organic or inorganic magnesium salts as such would be useful for treating warts.

The disadvantages related to conventional subcutaneous methods of treating warts are usually quite tedious treatments, which require patience and persistence, with long continuous periods of treatment. The subcutaneous treatment has to be combined with mechanical removal of the infected and treated skin. The warts can be quite painful and if the warts are irritated the compositions easily cause further irritation, stinging and to some extent even pains. In difficult cases the mechanical treatment can cause even inflammatory conditions. In order to avoid said disadvantages, it is desirable to provide an alternative therapy for treatment of warts. Such a therapy is provided in the present invention, which discloses a method for manufacturing a medicine comprising magnesium ions as an active ingredient for treatment of warts by oral administration.

The solution to the problem is provided by the present invention in which it is shown that orally admmistrable compositions comprising magnesium ions can be used for healing warts. The characteristics of the present invention are set forth in the claims.

The Summary of the Invention

The present invention provides a rapid and effective method for wart therapy by oral administration of magnesium salts. Positive results are obtained by a treatment, the durance of which is less than two weeks. Often positive results are obtainable in less than one week. The positive results, in form of complete disappearance of warts is observable in less than a week or two. The lack of side-effects of the medicine in combination with the easy and agreeable form of administration, the treatment can be repeated if the occurrence of warts recur. The present invention is related to the use of pharmaceutically acceptable, water-soluble, inorganic or organic magnesium salts, preferably magnesium sulphate salts, most preferably the Epsom salt, i.e. MgSO4.7H2O, for manufacturing an orally administrable, medically active composition for treatment of warts.

Because the composition of the present invention is intended for oral administration and in addition to the active ingredient, i.e. the magnesium salt, it can comprise one or several pharmaceutically acceptable, functionally inert, solid or liquid excipients, which facilitate tablet formation and/or improved solubility of the active ingredient. In its most preferred embodiment the composition is an effervescent tablet, which provides a fizzy drink.

Another preferred embodiment is to provide the magnesium ions as a composition comprising a pharmaceutically acceptable inert excipient such as a buffered or non-buffered aqueous solution, which may or may not include inert organic polyols, such as sugar alcohols and/or glycerol.

The Detailed Description of the Invention

Definitions

In the description which follows, most terms are used in the same way they are generally used in medical an pharmaceutical fields. However, some terms are used in a more extensive way. In order to provide a clearer and more consistent understanding of the specification and claims including the scope to be given such terms, the following definitions are given.

The term "magnesium salt" is used to mean inorganic or organic pharmaceutically acceptable salts of magnesium, which are dissolvable in water and provide an aqueous solution containing an amount of magnesium ions effective for treating warts. If not dissolvable the "magnesium salt" should be capable of providing an effective amount of absorbable magnesium ions in the stomach or intestines of the patient. The most preferred magnesium salt is magnesium sulphate, most preferably in the form of Epsom salt. Other acceptable inorganic magnesium salts are halogen salts of magnesium, such as MgCb. carbonates such as MgCO2- magnesium polyphosphonates, etc. As examples of organic magnesium salts, the following can be mentioned, fumarates. citrates, malates, maleates, maleinates. It is, however, to be observed that the organic salts should be in such form that the uptake of the magnesium salts in the intestines is not disturbed, for example by chelate formation.

The term "pharmaceutically acceptable" is used to mean that the ingredients do not cause any adverse or toxic effects on the patient and that they also fulfill the purity requirements of the pharmacopeia.

The term "water-soluble" is used to mean that the magnesium ions can be dissolved in an aqueous solution in an amount capable of providing an effective amount of the

The term "oral administration" is used to mean that the active ingredient is administered in the form of a drink or solution or in the form of tablets, granules or powders. The granules and powders can be administered in the form of capsules to facilitate easier swallowing. The most preferred form of oral administration is in the form of an effervescent drink.

The term "manufacture" is used to mean preparation and production of the medicine with conventional methods known to those skilled in the art.

The term "medically active composition" means a medicine, i.e. a formulations and/or preparation comprising magnesium ions as the active ingredient, optionally combined with functionally inert excipients, additives, fillers, stabilizers, lubricants, sweeteners, flavouring agents, etc.

The term "functionally inert" is used to mean that the substances used, in addition to the active ingredient, do not intervene with or disturb the effect of the active ingredient.

The term "solid excipient" is used to mean functionally inert solid excipients. additives, fillers, stabilizers, lubricants, sweeteners, flavouring agents frequently used in tabletting, including the manufacture of effervescent tablets.

The term "liquid excipient" is used to mean water as such or water in form of aqueous buffers and aqueous solutions containing electrolytes, as well as polyols, including sugar alcohols and glycerol. The term "aqueous" is used to mean a solution comprising water as its main ingredient.

The term "buffered" is used to mean that an aqueous solution in addition to the active ingredient contains electrolytes, including salts, acids and bases. Said electrolytes are responsible for giving the solution the desired pH, preferably a pH in the physiological region. In effervescent tablets "buffered" means that the tablet comprises substances, which when the tablet is dissolved, are capable of adjusting the pH of the solution in such a way that carbon dioxide is released and the drink has an agreeable acidity and/or taste.

The term "non-buffered" is used to mean a pure water-solution of the active ingredient with neutral excipients.

The term "solution" is used to mean the active ingredient as a preprepared aqueous solution or the drink obtained when an effervescent tablet is dissolved in water or some other acceptable liquid carrier, preferably with an agreeable taste.

The term "organic polyol compounds" is used to mean sugar alcohols such as sorbitol, mannitol, etc. , but above all glycerol.

The term "dissolvable" is used to mean capable of releasing such amounts of the active ingredient , i.e. the magnesium ion in the intestines that an effective amount for treating warts can be absorbed in the intestines. Alternatively, "dissolvable" means capable of forming a water-solution containing an effective amount of the active ingredient.

The term "effervescent" is used to mean bubbling, sparkling. The effect is obtainable by dissolving an effervescent composition in such an amount of a desired solvent, e.g. an aqueous solution, that a fizzy drink with agreeable mouth feel and taste still containing an effective amount of the active ingredient is formed.

The present invention describes the use of magnesium salts for manufacturing medicines for therapeutic use for treating warts. The magnesium salt should be pharmaceutically acceptable and easily dissolvable in water. Both inorganic and organic magnesium salts can be used as long as they are sufficiently water-soluble in ambient conditions to provide a solution comprising an effective amount of the active ingredient, i.e. magnesium or magnesium ions. Alternatively, if the magnesium salt is not sufficiently dissolvable to provide an effective amount of the active ingredient in the solution, it should, however, be in such a form that it can be released or dissolved in the stomach or intestines of the patient enabling the uptake of an effective amount of the active ingredient without causing any adverse side-effects.

The medicine is preferably prepared in such a way that it can be administered orally. Thus, it is advantageous to mix the magnesium salt, dissolved in water with one or more pharmaceutically acceptable, functionally inert liquid excipient. The preferred pharmaceutically acceptable inert excipients in the liquid formulation are aqueous, buffered or non-buffered solutions, optionally comprising physiological amounts of other electrolytes. In the liquid medicament solution, pharmaceutically acceptable, physiologically inert organic polyols such as sugar alcohols, including glycerol can be added. The aqueous solution can also be provided with pharmaceutically acceptable physiologically inert stabilizers and/or preservers as well as emulgants, sweeteners and/or flavouring agents. It is, naturally, a prerequisite of said additives, that they do not interact with the physiological function of the therapeutic activity of the magnesium salt.

Alternatively, the magnesium salt in solid form can be mixed with pharmaceutically acceptable, functionally inert solid excipients to form tablets, granules or capsules. The solid formulation can also be provided with pharmaceutically acceptable physiologically inert stabilizers and preservers, which do not interact with the physiological function and the therapeutic activity of the magnesium ions. It can also include conventional pharmaceutically acceptable and physiologically inert additives, which facilitate tablet production by improving the flowability and compressability of the tablets. Naturally, the solid compositions of the magnesium salt can be in the form of powders, granules, optionally incorporated in capsules.

In the most preferred embodiment of the invention, the most desired two properties of the orally administrable composition, i.e. the administration of a liquid composition as a taste agreeable drink and the storage stability of a solid composition, are combined. Said desired, advantageous properties are obtained by providing an effervescent tablet, which can be administered in an agreeable form as a bubbling drink with an agreeable taste and good mouthfeel. The effervescent composition contains such an amount of magnesium ions that when dissolved in a suitable solvent, preferably water, an effective amount of the active ingredient is present also in the final fizzy drink. The use of effervescent tablets provide an industrially feasible method for manufacturing an orally administrable solution in form of a drink for treating warts still provided with the improved stability and shelf-life connected with solid formulations, such as tablets. The effervescent tablets can be prepared by several conventional methods known to those skilled in the art. In one preferred embodiment of the invention the magnesium ions are provided in the form magnesium carbonate. The sparkling effect of the liquid is obtained by other physiologically inert pharmaceutically acceptable additives, which allow the release of carbon dioxide, but do not cause the magnesium ions to precipitate or form inaccessible complexes. In another preferred embodiment of the invention the sparkling effect is obtainable by using sodium bicarbonate as the carbon dioxide source.

The invention is described in more detail in the following examples and experiments, which are disclosed in order to clarify the invention but should not be interpreted to limit the scope of invention. Based on these examples and experiments one skilled in the art knows how to develop corresponding medicaments with the same effect.

Example 1

The manufacture of a magnesium sulphate solution

Magnesium sulphate 20 g

Aq. purif. 280 ml

The ingredients were mixed together in ambient temperature to give 300 ml of solution in a glass bottle.

Experiments

The experiments were performed as described below by treating the patient by orally administation to the patient a solution containing the active ingredient or placebo.

The active ingredient was administered in the form of a solution prepared as described in example 1. The placebo-solution contained water and sorbitol.

Patient 1:

Sex: Female

Age: 40 years

Weight: 60 kg

Diagnose: The patient presented with several warts on the back of the left and the right hand as well as on the arms. Some of the warts were irritated.

Treatment: The patient was treated by administering 300 ml of the solution containing the active ingredient in doses of 15 ml thrice a day for one week. During the treatment no side effects could be observed.

Effect: In two weeks after the treatment the warts had disappeared completely and the skin was totally healed.

Patient 2: Sex: Male Age: 44 years Weight: 110 kg

Diagnose: The patient presented with two large warts in the face.

Treatment: The patient was treated by administering 600 ml of the solution containing the active ingredient in doses of 15 ml thrice a day for two weeks. During the treatment no side effects could be observed.

Effect: The warts healed in one week after the termination of the treatment and the new skin was completely healthy.

Patient 3: Sex: Male infant Age: 7 years Weight: 25 kg

Diagnose: The patient presented with several warts in the palms, on the back of the hands, on the arms, face and back. Some of the warts showed severe irritation.

Effect: Within two weeks after the treatment the warts disappeared and the skin was totally healed.

Patient 4: Sex: Female Age: 15 years Weight: 44 kg

Diagnose: The patient presented with several warts under the feet and on the toes.

Treatment: The patient was treated with 300 ml of the solution containing the active ingredient by administering doses of 15 ml thrice a day for one week. During the treatment no side effects could be observed.

Effect: Within two weeks after the treatment, the warts healed and the new skin was healthy.

Patient 5: Sex: Male Age: 24 years Weight: 90 kg

Diagnose: The patient presented with warts on the bottom of the left and right feet.

Effect: Within one and a half week after the treatment the warts disappeared and the skin was healthy. 10

Patient 6: Sex: Male Age: 29 years Weight: 75 kg

Diagnose: The patient presented with several warts on the back of the left hand.

Treatment: The patient was treated by administering 300 ml of placebo solution. The dosage was 15 ml thrice a day for one week.

Effect: No effect on the warts could be observed.

Patient 7: Sex: Female Age: 20 years Weight: 56 kg

Diagnose: The patient presented with warts on the fingers of the left and right hand.

Effect: No effect on the warts could be observed.

Patient 8: Sex: Male Age: 16 years Weight: 69 kg

Diagnose: The patient presented with several warts on the palms and on the back of the left and the right hand as well as on the fingers.

Treatment: The patient was treated by administering 300 ml of placebo 11

solution. The dosage was 15 ml thrice a day for one week.

Effect: No effect on the warts could be observed.

Patient 9: Sex: Male

Age: 39 years Weight: 82 kg

Diagnose: The patient presented with several warts on the forehead and on the fingers of the left hand.

Effect: No effect on the warts could be observed.

Patient 10: Sex: Male infant Age: 7 years Weight: 25 kg

Diagnose: The patient presented with several warts on the palms and the back of the left and the right hand, on the arms, the face and the back. Some warts were seriously irritated.

Effect: No effect on the warts could be observed.

Patients 6-10

The treatment of patients 6-10 was renewed with a solution containing the active ingredient. The effect on all patients 6-10 was as described above for the patients 1-5.

Claims

12CLAIMS

1. The use of pharmaceutically acceptable magnesium salts for manufacturing medically active, orally administrable compositions for treatment of warts.

2. The use according to claim 1, characterized in, that the magnesium salt is a pharmaceutically acceptable, organic or inorganic magnesium salts.

3. The use according to claim 2, characterized in, that the magnesium salt is a pharmaceutically acceptable, magnesium sulphate.

4. The use according to claim 3, characterized in, that the magnesium salt is water-soluble.

5. The use according to any of claims 1-4, characterized in, that the composition comprises in addition to the magnesium salts, one or more pharmaceutically acceptable, functionally inert, solid excipients.

6. The use according to any of claims 1-5, characterized in, that the composition is an effervescent tablet, which upon dissolving provides a fizzy drink for treating warts.

7. The use according to any of claims 1-5. characterized in, that the composition for treating warts by oral administration is a solid formulation, selected from a group consisting of tablets, capsules, powders or granules.

8. The use according to any of claims 1-4, characterized in, that the composition is a solution, which in addition to the water-soluble magnesium salt comprises one or more pharmaceutically acceptable, functionally inert, liquid excipients.

9. The use according to any of claims 1-4 or 8, characterized in. that the liquid excipient is water.

10. The use according to any of claims 1-4 or 8. characterized in. that the liquid excepient is an aqueous, buffered or non-buffered solution optionally comprising physiologically inert polyols.