CZ2004929A3 - Stabilization dispersive base for photodynamic diagnostics and therapy - Google Patents

Abstract

The stabilizing dispersion base for photodynamic diagnostics and therapy consists of 5 to 20% by weight of 5-aminolevulinic acid hydrochloride, 0.05 to 0.33% by weight of succinic acid, an alkaline substance in a weight% range that is directly proportional to the pH range of 3 to 6 in the final solution, all with purified water.

Description

Technical field

The invention relates to a product which is a dispersion basis for photodynamic diagnostics and therapy, which can be used in medicine for a more stable course of diagnosis and treatment of cancer, viral and other types of diseases. It can also be used in the cosmetics sector.

BACKGROUND OF THE INVENTION

At present, the problems in the field of preparations of stabilization of dosage forms for photodynamic diagnostics and therapy are solved in principle only by means of antioxidant substances. Photodinamic diagnostics and therapy which are utilized with the preparations already known but also solved by the present invention are used for the diagnosis of precanceroses, virus-infected cells but also other diseases. Examples of use of the product in photodynamic diagnostics and therapy are, for example, the treatment of skin cancer, bladder cancer, gynecology organs, but also for the treatment of psoriasis, warts removal. In the case of dispersion solutions in the form of emulsion or gel application preparations for photodynamic diagnostics and therapy, which are solved by the Czech utility models Nos. 11007, 11008, 11009 and also by the published Czech patent application No. 2000-2783 and the following patent application international stability of applied products in diagnosis or treatment. Some of the ingredients of the dosage form utilized for the above protection have shown significant new effects in diagnosis and therapy. The most important of these is 5-aminolevulinic acid hydrochloride. However, this is insufficiently stable when applied. Despite the preparation just prior to application, the product gradually loses its stability and there is a loss of effectiveness of the product, accompanied by darkening and decomposition. In the cooling box the product lasted a maximum of 5 hours, at room temperature only a few tens of minutes. This results in reduced efficacy of these expensive preparations, but also in their depreciation in the case of • 4

2.

• 444 product preparation in case of stocking or poor mixing of the product before application. Leaving the composition of the preparation just prior to its application to the human factor, quite often, results in errors manifested by non-compliance with the prescribed conditions and the consequent negative consequences described above. Thus, these properties of the formulation do not allow the factory manufacture of the final product.

The essence of the invention

These drawbacks are eliminated by the stabilizing dispersion basis for photodynamic diagnostics and therapy of the present invention, which consists of 5 to 20% by weight of aminolevulinic acid hydrochloride, which is the carrier for diagnosis and treatment. The other component, present in an amount of 0.05 to 0.35% by weight of succinic acid, has a stabilizing effect on the final formulation in combination with alkaline substances. The alkalis are supplied in a weight% range such that the final formulation reaches a pH range of 3 to 6. All supplemented with purified water, which is essentially distilled water.

It is preferred that the alkaline substance contained in the article is NaOH.

It is also preferred to use KOH as the alkali.

It is also preferred that the alkali is triethanolamine.

It is further preferred that the article comprises an antioxidant in the form of ascorbic acid, which also increases the stability of the article to some extent.

It is also suitable that the product contains a component in the form of methylcellulose, which causes the required gel consistency of the product.

It is also preferred that the article comprises a lanthanum rubber component which also causes the desired gel consistency of the article.

Furthermore, it is suitable that the product comprises arlamol HD, perliquidum paraffins and atlas G-2330, which are ingredients that cause creamy consistency.

It is also preferred that the product comprises an arlacel P-135 emulsifier.

It is also desirable that the product comprises a mithon additive which contributes to the preservation of the product.

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Known dosage forms for photodynamic diagnostics and therapy had to be prepared from the ingredients into the finished product solution just prior to use. When absorbed into cells of, for example, skin cells, it was necessary that the crushed active ingredient of the product was absorbed for up to two hours. This time limit was insufficient for a poorly stable product. The new product is much more stable than the described prior art products.

In a cool box at around 7 ° C, its shelf life is guaranteed for at least a year. The product is stable for tens of hours at room temperature. The essence of the stabilizing components is succinic acid in solution with a dosage form which contains one of the alkali components such as sodium hydroxide, potassium hydroxide triethanolamine and the like. The alkaline substance is present in the solution of the whole product in an amount ensuring a degree of pH in the range of 3-6. There is no loss of product performance or decomposition during application. The process of diagnosis and therapy using a new product is therefore highly effective, the product is 100% utilized and it is also saved, which is essential at its selling price.

Use of the product is very simple, it spreads on the skin or it is saturated with a solution of this substance instead of a controlled or treated organ. It is allowed to act for about 1 to 2 hours, after which it is diagnosed with blue light having a wavelength of 420 nm. The 5-aminolevulinic acid hydrochloride contained in the stabilizing base has the property of being absorbed more into cells that have greater metabolism. They are both malignant and benign tumor cells. This hydrochloride, when exposed to blue light, is fluorescent, becomes a photosensitizer and emits red fluorescent light. Cells with greater metabolism therefore glow red strongly and become visible.

In the case of therapy, the procedure with the product is the same, for the treatment of tumor or virus-infected cells, light red having a wavelength of 660 nm is used instead of blue light. This light is allowed to act for about 1 hour. The principle of treatment is that the photosensitizer, which is again 5-aminolevulinic acid hydrochloride or its derivatives, when exposed to red light causes the release of singlet oxygen and its radical, which acts on the tissue and

4 · 4444 • 4 4 • 4 4 • 4 4 • 4 ·· 44 ·

• 4 4

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4 444 • · 4 • 4 4 the more the photosensitizer concentration in the tissue is higher. The energy of radiation is then applied in the destruction of diseased cells. Diagnostics with the help of the mentioned product is very conclusive. Treatment of cancer or viral diseases does not require postoperative intensive care, does not require the cost of isotopic treatment, has no side effects compared to chemotherapy, does not require blood transfusions.

DETAILED DESCRIPTION OF THE INVENTION

Example 1.

The stabilizing dispersion base for photodynamic diagnostics and therapy is in this case a gel-based product. The gel form is provided by methylcellulose. The product achieves a pH of 4.5. Product composition: 5-aminolevulinic acid hydrochloride 20% by weight methylcellulose ascorbic acid sodium hydroxide succinic acid purified water% by weight 0.5% by weight 7.78% by weight 0.06% by weight 66.66% by weight

Example 2.

The stabilizing dispersion base for photodynamic diagnostics and therapy is in this case a gel base product. The gel form is provided by xanthan gum. The product achieves a pH of 5.5. Product composition: 5-aminolevulinic acid hydrochloride 15% by weight xanthan gum Ascorbic acid potassium hydroxide succinic acid purified water

1.5% by weight 0.5% by weight 9.06% by weight 0.06% by weight 73.88% by weight

Example 3.

• · ·

The stabilizing dispersion base for photodynamic diagnostics and therapy in this case is a product based on an oily cream base. The cream form is provided by the components arlamol HD, paraffins perliquidum, atlas G-2330.

The product achieves a pH of 3.4. Composition of the product;

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5-aminolevulinic acid succinic acid triethanolamine arlacel P-135 arlamol HD paraffins perliquidum atlas G-2330 mithon purified water% by weight

0.12% by weight 4.3% by weight 2% by weight% by weight% by weight

0.07% by weight 67.51% by weight

Due to the very different weight% of the individual alkaline substances used in the product, the range of these alkaline substances is limited by the achieved pH level of the final product. The alkaline component directly affects the pH.

Industrial applicability

The solution is applicable with regard to achieving sufficient product stability in large-scale specialized pharmaceutical-type operations.

Claims (10)

PATENT REQUIREMENTS 9 9 9 9 9 9 99,999 9 · ··· · A stabilizing dispersion basis for photodynamic diagnostics and therapy, characterized in that it consists of 5 to 20% by weight of 5-aminolevulinic acid hydrochloride, 0.05 to 0.35% by weight of succinic acid, an alkali in the range of% by weight, which are directly proportional to pH range 3 to 6 in final solution, all supplemented with purified water. Product according to claim 1, characterized in that the alkaline substance is sodium hydroxide. Product according to claim 1, characterized in that the alkaline substance is potassium hydroxide. 4. The article of claim 1 wherein the alkali is triethanolamine. Product according to at least one of the preceding claims, characterized in that it comprises a substance in the form of ascorbic acid. Product according to at least one of the preceding claims, characterized in that it comprises a component in the form of methylcellulose. Product according to at least one of the preceding claims, characterized in that it comprises a lanthanum rubber component. Product according to at least one of the preceding claims, characterized in that it comprises a component which is arlamol HD, perliquidum paraffins and atlas G-2330. 99 9999 99 99 9 9 9 9 9 9 • 999,999 9 9 9 9 9 · 99 99 99 9 9 9 9 9 9 9 9 9999 9 9 9 99 · An article according to at least one of the preceding claims, characterized in that it comprises arlacel P-135. Product according to at least one of the preceding claims, characterized in that it comprises a mithon additive.