IE912392A1 - Pharmaceutical, vaginal applicable preparation - Google Patents

Abstract

The vaginal pharmaceutical preparation is characterised in that it contains at least one water-soluble polyvinyl alcohol, at least one component A selected from the group consisting of wetting agents, non-ionic surface-active agents and dispersants, and at least one active substance B for the local treatment of sexually transmissible or transmitted diseases, and/or vaginal disorders, and optionally one or more auxiliary or auxiliaries, in homogeneous dispersion, and is in the form of a film with a thickness of 0.05 to 0.5 mm, in particular 0.06 to 0.2 mm, preferably 0.07 to 0.15 mm.

Description

Pharmaceutical. vaginal applicable preparation The present invention is directed to a pharmaceutical, vaginal applicable preparation.

For the pharmaceutical treatment of vaginal 5 diseases are used usually vaginal tablets, ointments, gels, foams and ovuli. Each of these administrative forms has advantages and disadvantages. From the disadvantages are mentioned: bad decomposition of the preparation, foreign body feeling, bad distribution of the respective active component in the vaginal mucosa, complicated dosage, for example by means of an applicator. A foam may cause an unpleasant feeling and thus may be refused because of objective and/or subjective reasons. Furthermore, it is known a so-called C-film for the prevention of pregnancy.

It is an object of the present invention to provide a new galenic form, i.e. a film for the proportioned release of the active components for the local treatment of sexual transmissible or transmitted, respectively, diseases, and/or for vaginal affections.

This new galenic form shall distribute the active components on the vaginal mucosa relatively quick, good and uniform. In addition, also the stability of the active compounds, which are present in the film, shall be in25 creased.

These objects are obtained in an excellent way with the inventive preparation.

The inventive pharmaceutical, vaginal applicable preparation is characterized in that it contains, homogeneously sub-divided, at least one in water soluble polyvinyl alcohol, at least one component A, selected from the group consisting of wetting agents, non-ionic surface active agents and dispersing agents, as well as at least one active component B for the local treatment of sexual transmissible or transmitted, respectively, diseases, and/or for vaginal affections, and occasionally one or more auxiliary agent(s), and in that it is in the form of a film having a thickness of the layer of from 0.05 to 0.5 mm, especially from 0.06 to 0.2 mm, preferably from 0.07 to 0.15 mm.

Preferred embodiments of this invention are defined in the dependent claims.

In the following a possible preparation of the inventive preparation (film) is described.

A in water soluble polyvinyl alcohol, for example Poval 205 of the firm Kuraray Co. Ltd., Japan, is mixed with at least one of said component A, for example a mixture of at least one nonoxynol, such as nonoxynols of the formula c9h19-c6h4—och2ch2-ftr oh wherein n is an integer, preferably 9 or 10, and glycerin, and with water. This mixture is then heated, for example to a temperature of about 90 °C. It is preferred to filter the cooled solution, for example at a temperature of about 50 °C. If the active component B and the optional auxiliary agents are soluble in water, then they are dissolved in water and are added to the mixture preferably before the filtration. If the active component B and the optional auxiliary agents are not soluble in water, then they are added to the mixture afIE 912392 ter said filtration, preferably under stirring, for example in the form of a suspension or an emulsion, whereby aqueous suspensions or aqueous emulsions are preferred. Water-in-oil microemulsions and oil-in-water microemulsions are also applicable. It is also possible to add an in water not soluble active component B and/or auxiliary agent to the filtered mixture in solid form, preferably under stirring, especially then when the suspension becomes homogenized. It is also possible to add the active component B and/or auxiliary agent, dissolved in at least one organic solvent, to the mixture.

In this kind of addition no separation of the phases between the organic solvent and water shall occur. If necessary for the corrosion protection of film preparation devices the filmcasting solution may be buffered.

Said filtration is carried out in order to remove impurities, which may occasionally be present, such as water insoluble polymers of polyvinyl alcohol, dust and further foreign substances. In the case of absolutely pure and uniform products, the filtration can be omitted. The filmcasting solution must be homogeneous. Occasionally present air bubbles can be removed by leaving the solution to rest or by treating under vacuum or by performing a gentle agitation.

This filmcasting solution can now be processed in many manners, in the conventional way, in order to obtain a film.

According to a first method, the filmcasting 30 solution is batch poured into a tub which has the dimensions desired. Then, the water and the occasionally preIE 912392 sent organic solvents are removed by drying. The drying can be carried out, for instance, by means of hot air, coming from a suitable hair-dryer, or coming from a suitable thermic lamp, for example an infra-red lamp. The temperature used must be such that no component is chemically transformed, especially decomposed, by the influence of heat.

The film can now be subjected to an embossing, thus increasing its surface and gripping capacity. The film is finally cut and ancillary processed, for instance packed into bags, and if necessary made sterile by a suitable irratiation method.

According to a second method, the filmcasting solution is processed continuously in a filmcasting de15 vice. Thereby the filmcasting solution is poured onto a continuous tape through a slot nozzle. The film support is usually a strip of chrome steel polished to obtain high brightness. When pouring, the viscosity of the filmcasting solution must be such as to flow still, but not to stop.

The used viscosity depends among other things on the type of machine. The continuous tape, coated with the filmcasting solution, enters a drying tunnel, where the water and the organic solvent, which is occasionally present, are removed. The temperature in the drying tunnel must be such that no component is chemically transformed, especially decomposed, by the influence of heat. At the end of the drying tunnel, the film contains only a few percents by weight of water, for example about 5 % by weight of water. The desired film thickness can be controlled and regulated by using a computer. If, when starting, the film is too thin, then the slot nozzle is automatically opened a little bit. On the contrary, if the film is too thick, then the slot nozzle is closed a little bit.

With regard to the embossing, cutting and type 5 of packaging, reference is made to the above corresponding statements.

The component B for the local treatment of sexual transmissible or transmitted, respectively, diseases, and/or for vaginal affections is especially an active component for the local treatment of bacterial or viral infections, or an active component for the local treatment of diseases caused by fungus7 or trichomonas.

Examples are: benzalkoniumchloride, neomycins, such as neomycin-B-sulfate, polymyxins, such as polymy15 xin-B-sulfate, econazol, econazolnitrate and metronidazol.

These and still further active compounds, including a placenta extract, may be mixed with a nonoxynol, for example a nonoxynol of the formula C9H19 — C6H4-f- OCH2CH2irr 0H wherein n is an integer, preferably 9 or 10. Nonoxynol-9 and nonoxynol-10 are preferred, especially then when these compounds fulfill the prescriptions according to USP 22.

The inventive preparation is very easy to be applied. It can, cut to the desired dimensions, for example 5 x 5 cm, be introduced into the vagina by a finger. A foreign body feeling, if any, is only felt in the first minutes. By the influence of body heat and/or due to secretions, which are present in the vagina, the active component(s) contained in the film exhibit a better and more homogenous actions, in comparison with other, above all solid galenic forms. The pharmaceutical effect to be obtained depends on the used combination of active components.

The following examples shall illustrate the present invention.

Example 1 Vaginal preparation against bacterial infections A mixture of 4.53 kg of polyvinyl alcohol Poval 205 of the firm Kuraray Co, Ltd., Japan, 360 g of glycerin, 2.16 kg of nonoxynol-9 and 600 g of benzalkoniumchloride was slowly warmed to a temperature of 90 °C in 17.35 kg of water under stirring. When all components had dissolved the slightly cloudy solution was cooled and filtered at a temperature of 50 °C. The clear filtrate was allowed to stand at a temperature of 45°C during 30 minutes, whereupon in the mixture no air bubbles were present. With this filmcasting solution was prepared on a filmcasting machine a homogeneous film with a thickness of 0,09 mm. The filmcasting solution was poured at a temperature of 40°C to 50°C.

Example 2 Vaginal preparation against trichomonas A mixture of 453 mg of polyvinyl alcohol Poval 205 of the firm Kuraray Co, Ltd., Japan, 36 mg of glyce5 rin, 216 mg of nonoxynol-9 and 100 mg of metronidazol was dissolved in 10 ml of water and heated to a temperature of 90 °C under stirring. The slightly cloudy solution was cooled and filtered at a temperature of 50 °C. This filtrate was poured into a rectangular tub (5 x 10 cm) and dried with a heat lamp (Biccatherm-lamp). There was obtained a homogeneous film having a thickness of 0.075 mm.

Example 3 Vaginal preparation for the control of fungus7 A mixture of 3.01 kg of polyvinyl alcohol Poval 205 of the firm Kuraray Co, Ltd., Japan, 240 g of glycerin and 1.0 kg of nonoxynol was slowly warmed to a temperature of 90°C under stirring in 13.35 kg of water. The slightly cloudy solution was cooled and filtered at a temperature of 50°C. To this clear filtrate was added under stirring a slurry of 400 g of finally grinded econazol in 2.0 kg of water at a temperature of 35 °C. This mixture was slightly stirred at a temperature of 35°C during 30 minutes, whereupon in the mixture no more air bubbles were present. With this filmcasting solution was prepared a homogeneous film with a thickness of 0.07 mm on a filmcasting machine. The filmcasting solution was poured at a temperature of 35 °C.

Claims (8)

Claims

1. A pharmaceutical, vaginal applicable preparation, characterized in that it contains, homogeneously sub-divided, at least one in water soluble polyvinyl al5 cohol, at least one component A, selected from the group consisting of wetting agents, non-ionic surface active agents and dispersing agents, as well as at least one active component B for the local treatment of sexual transmissible or transmitted, respectively, diseases, 10 and/or for vaginal affections, and occasionally one or more auxiliary agent(s), and in that it is in the form of a film having a thickness of the layer of from 0.05 to 0.5 mm, especially from 0.06 to 0.

2. Mm, preferably from 0.07 to 0.15 mm. 15 2. The preparation according to claim 1, characterized in that the active component B is an active component for the local treatment of bacterial or viral infections, for example benzalkoniumchloride, a neomycin, such as neomycin-B-sulfate, or a polymyxin, such as 20 polymyxin-B-sulfate, or an active component for the local treatment of diseases caused by fungus' or trichomonas, for example econazol, econazolnitrate, metronidazol, or an active component for the treatment of vaginal mucosa affections, for example a placenta extract, whe25 reby these active components occasionally may be mixed with at least one nonoxynol, such as nonoxynols of the formula C 9 H 19 - C 6 H 4 -(- OCH 2 CH 2 tn- θ Η wherein n is an integer, preferably 9 or 10.

3. The preparation according to one of claims 1 to 2, characterized in that the component A is selected from monovalent alcohols, for example a nonoxynol, such as nonoxynol-9, nonoxynol-10, and polyvalent alco5 hols, for example propylene glycol, glycerin, and is especially a mixture of a nonoxynol and glycerin.

4. The preparation according to one of claims 1 to 3, characterized in that it contains from 50 to 70 % by weight, especially from 55 to 65 % by weight, of 10 a polyvinyl alcohol, from 15 to 35 % by weight, especially from 20 to 30 % by weight, of nonoxynol, from 3 to 8 % by weight, especially 5 % by weight, of glycerin, and up to 15 % by weight of active component B, whereby the total of all components, including the occasionally 15 present auxiliary agent(s), gives always 100 % by weight.

5. The preparation according to one of claims 1 to 4, characterized in that the auxiliary agents are selected from the group consisting of stabilizers, 20 plasticizers, buffers, antioxidants, perfumes and dyes, and in that they are present always in active concentrations .

6. The preparation according to one of claims 1 to 5, characterized in that the surface of the film is 25 increased by means of embossing.

7. A pharmaceutical preparation as defined in Claim 1 and substantially as described herein.

8. A method of preparing a pharmaceutical preparation as defined in Claim 1, substantially as described herein by way of Example.