Pharmaceutical composition with a photosensitizer

 

(57) Abstract:

The ointment can be used in medical practice when conducting photodynamic therapy of malignant tumors. The ointment composition, wt.%: hematoporphyrin, or its derivatives, or liposomal form of hematoporphyrin, or damagin 0, 07-2,0, dimethylsulfoxide or Dimexidum 30-45, fat basis - the rest. The invention allows to expand the range of formulations for photodynamic therapy of tumors.

The invention relates to pharmaceutical industry and relates to the creation of new dosage forms in the form of ointments with photosensitizers that may be used in medical practice, in particular when performing photodynamic therapy.

It is known in the medical use when conducting photodynamic therapy of malignant tumors of basic locations as photosensitizers derived hematoporphyrin different purity under various trade names, for example, photosan, Photohem, Photofrin I, Photofrin II.

However, to date these drugs have been used in the dosage form in the form of injection solution. Introduction 0 mg/kg of body weight of the patient, in terms of finding the patient in a darkened room within 48-72 hours prior to laser irradiation of the tumor. Studies show that the use of injectable dosage forms of photosensitizers in some cases leads to pronounced changes of oxidative-antioxidative balance, which clinically manifests as inflammatory reaction, often accompanied by swelling of the tissue. The presence of such complications necessitates the development of new dosage forms of photosensitizers for use in medical practice when conducting photodynamic therapy.

Known composition for photodynamic therapy of tumors, which can be an ointment, gel, cream or solution (US 4753958). This composition contains, as a photosensitizer, hematoporphyrin derivatives. As auxiliary materials it may contain water, liquid alcohols, liquid glycols, liquid lanolin and other compulsory component in the number of carriers is N-organic. For local applications, it is recommended that a combination of media called "AZONE" in combination with N - organic.

The invention has been p the/P> According to the claimed invention features a pharmaceutical form in the form of ointments, containing a photosensitizer hematoporphyrin or hematoporphyrin derivatives, or liposomal form of hematoporphyrin, or demagin in the amount of 0.07 to 2.0 wt.%, the solvent is dimethyl sulfoxide, dimexide in the amount of 30% - 45% fat basis - the rest.

As forming ingredient is a fatty basis can be used vaseline and/or lanolin.

As a photosensitizer composition can contain a variety of hematoporphyrin derivatives, such as hematoporphyrin dimer (Photofrin I, Photofrin II, Photohem, photosan), and oligomers of hematoporphyrin containing 8 molecules. The above solvents are not more than 30 ml of 45%, as a further increase in the number of solvent only leads to unnecessary consumption of the reagent and to a more liquid consistency of the ointment, which, in turn, can cause the spreading ointment when applied to the skin of the patient, and decline leads to incomplete dissolution of the photosensitizer. When used as photosensitizers liposomal form of a derivative of hematoporphyrin or liposomemediated buffer.

The method of obtaining the claimed composition in the form of ointments involves the dissolution of attachment of the photosensitizer in the above-stated amount of solvent, heating the solution up to 35 - 40oC and the injection solution in the mass, containing a fatty basis vaseline and/or lanolin.

The invention is illustrated by the following not limiting examples.

Example 1 N preparation of 0.25 wt.% ointment with hematoporphyrin.

Dissolve 0.25 wt.% hematoporphyrin in 35,3% by weight dimethyl sulfoxide. The solution is heated to 40oC and poured with vigorous dissolution in the mass, containing as ointment bases 44,45 wt.% vaseline and 20 wt.% lanolin. The resulting mass is stirred until a homogeneous state and kept in a container made of dark glass.

Example N 2 preparation of 0.07 wt.% ointment with hematoporphyrin derivative in an alkaline buffer with a pH of 8.3.

Dissolve 0.07 wt. % of a derivative of hematoporphyrin in 35,3% by weight dimethyl sulfoxide. Perform filtering using the filter. Heated to 40oC and pour in the mass, containing 30 wt.% vaseline and 34,63 wt.% lanolin. The resulting mass is stirred until a homogeneous state and kept in a container made of dark glass.

Example 3 preparation of 2.0 the solution is heated to 40oC and poured with vigorous dissolution in the mass, containing as the basis of 42.7 wt.% vaseline and 20 wt.% lanolin. The resulting mass is stirred until a homogeneous state and kept in a container made of dark glass.

Example # 4 preparation of 0.5 wt.% ointment with imaginem.

Dissolve 0.5 wt.% imagina in 35,3% by weight Dimexidum. The solution is filtered and heated to 35oC and poured with vigorous dissolution in the mass, containing as the basis of 44.2 wt.% vaseline and 20 wt.% lanolin. The resulting mass is stirred until a homogeneous state and kept in a container made of dark glass.

Example N 5 preparation of 0.5 wt.% ointment with hematoporphyrin.

Dissolve 0.5. % of hematoporphyrin in to 44.5 wt.% dimethyl sulfoxide. The solution is heated to 40oC and poured with vigorous dissolution in the mass, containing as the basis of 40 wt.% vaseline and 15 wt.% lanolin. The resulting mass is stirred until a homogeneous state and kept in a container made of dark glass.

Example N 6 preparation of 0.07 wt.% ointment with liposomal hematoporphyrin derivative.

Dissolve to 0.025 wt.% liposomal forms of hematoporphyrin in 35,3% by weight dimethyl sulfoxide. The solution is heated to 35oC and pour in online at the SSA stir until a homogeneous state and kept in a container made of dark glass.

Examples of therapeutic efficacy of the inventive pharmaceutical compositions.

Example N 7

Patient A., age 64. Diagnosis: basal cell carcinoma of skin of the wing of the nose to the right.

On the surface ulcers caused ointment containing 0.07 wt.% hematoporphyrin derivatives. After hours of exposure produced by irradiation with radiation of copper vapor laser for 15 minutes. At the control examination after 1 month of data for the presence of basal cell carcinoma no.

Example 8

Patient P., 72 years. Diagnosis: lymphoma of the skin right thigh.

On the surface of the tumor caused ointment containing 2.0 wt.% hematoporphyrin. After 1.5 hours of exposure, the tumor is irradiated with radiation of copper vapor laser for 20 minutes. Two weeks after the session photodynamic therapy showed complete epitelizatia sores at the place of lysed tumor.

Examples of the results of a clinical study ointments with photosensitizer evidence of its clinical effectiveness. It should be noted that in each case depending on the depth and nature of the capillary dysplasia, use the ointment with a certain amount of photosensitizer.

Pharmaceutical composition with photosensibility is on contains as a photosensitizer hematoporphyrin, or hematoporphyrin derivatives, or liposomal form of hematoporphyrin, or demagin in the amount of 0.07 to 2.0 wt.%, the solvent is dimethyl sulfoxide or Dimexidum in the amount of 30 to 45 wt.%, fat basis - the rest.

 

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