RU104458U1 - MICROCONTAINER POLYMERIC WITH A MEDICINAL SUBSTANCE, ENSURING A LOCAL PROLONGED ANTITUMER ACTION - Google Patents

Abstract

The utility model relates to medical devices and can be used in traumatology and general surgery for application to wound surfaces of internal organs and tissues. The microcontainer consists of two parts: the central part, made in the form of granules with a described diameter of 0.05 to 1.5 mm, made of a copolymer of vinylpyrrolidone with butyl methacrylate and an antitumor substance and an outer shell of a copolymer of vinyl pyrrolidone with butyl methacrylate, with a thickness of 0.05 up to 0.2 mm. Using a utility model provides effective sorption of wound exudates, local prolonged antitumor activity for 8-40 days and reduces the total dosage of the used antitumor s substances in 8-350 times.

Description

The utility model relates to medical devices, namely, to products used in the treatment of oncological diseases.

Oral administration of hemostatic drugs in the form of tablets, for example, metatrixate, is known. (M.D. Mashkovsky Medicines, 2007, M., p. 982). This method of administration has a number of disadvantages:

- the tool has low bioavailability,

- the drug substance is partially destroyed by the liver,

- high total dosages per course of treatment, which leads to undesirable side effects.

Intravenous administration of antitumor drugs, for example, fluorouracil, is known by means of a dropper equipped with a needle. (M.D. Mashkovsky Medicinal substances 2007, M., p. 858-859). This method of administration has the following disadvantages:

- accompanied by injury to body tissues,

- requires repeated administration of the drug (up to 6-10 infusions),

- not able to provide the necessary local prolonged therapeutic effect,

- requires the introduction of large total doses of the drug substance, which can cause unwanted adverse reactions of the body and which leads to an increase in the cost of treatment.

The technical task of the proposed utility model is the creation of microcontainers from biocompatible polymers containing antitumor substances capable of absorbing postoperative exudates after application to the wound surface; capable of resolving after surgery within the body; capable of exerting a long-term local antitumor effect in the area of tissues adjacent to the site of the removed tumor and capable of significantly reducing the total dosage of antitumor drugs per treatment course ..

The technical result is achieved in that the microcontainer consists of two parts: the central part in the form of granules with a described diameter of 0.05 to 1.5 mm, made from a copolymer of vinylpyrrolidone with butyl methacrylate and an antitumor substance in the following ratio of constituent parts (% wt.) :

vinylpyrrolidone copolymer with

butyl methacrylate 65.0-90.0; antitumor substance 10.0-35.0

and an outer shell of a copolymer of vinylpyrrolidone with butyl methacrylate, with a thickness of 0.05 to 0.2 mm.

The boundary size of the granules is due to the fact that granules with a size of less than 0.05 mm do not provide the necessary duration of the release of antitumor substances into tissues adjacent to the resection zone, and granules with a size of more than 1.5 mm can cause an undesirable reaction of adjacent tissues to a foreign body due to mechanical the irritating effect of large solid particles. The thickness of the protective outer layer of less than 0.05 mm does not ensure the continuity of the protective layer, which does not allow to regulate the rate of release of the drug substance, and the thickness of more than 0.2 mm leads to an increase in the size of the microcontainer, which can cause an undesirable reaction (irritation) of surrounding tissues.

The granules and the outer shell are made of a biocompatible copolymer of vinylpyrrolidone with butyl methacrylate, which is able to completely biodegrade in the body within 14 to 60 days depending on the size of the particles and the implantation site without having a toxic effect on the surrounding tissues and the body as a whole. Antitumor substances undergo metabolic processes and are completely excreted from the body in terms determined by their structure and properties.

The amount of antitumor substance is from 10.0 to 35.0%. The boundary concentrations of antitumor substances are due to the fact that when the content of the antitumor substance is less than 10%, the necessary local therapeutic concentrations in the adjacent tissues are not achieved, and at concentrations of more than 35%, the porosity of the microcontainer increases, which reduces the duration of the release of the drug substance a, therefore , duration of antitumor activity.

The use of a polymer microcontainer containing an antitumor substance allows the following:

- to ensure reliable fixation of particles on the wound surface due to the high adhesion of the copolymer to soft tissues,

- provide sorption of wound exudates from the wound surface,

- eliminate the unwanted reaction of tissues to a long stay of a foreign body inside the body due to the complete biodegradation of the material,

- provide a long-term local antitumor effect;

- reduce the number of injections of the drug;

- reduce the total dose of the used antitumor substance.

The proposed Utility Model operates as follows.

At the end of the operation, immediately before tissue suturing, all layers of the surgical wound are uniformly sprinkled with a non-continuous layer of microcontainers, be sure to avoid the formation of a continuous layer or a heterogeneous thick layer. After applying microcontainers, the wound is sutured in layers tightly or with drainage.

Examples of manufacturing a utility model.

Example No. 1.

20 g of a copolymer of vinylpyrrolidone with butyl methacrylate grade PPB-1 (TU 2216-025-17712304-04) (80%) and 5 g of fluorouracil (20%) are dissolved in 50 g of ethyl alcohol, the resulting solution is poured onto a polypropylene substrate, dried in vacuum at a temperature of 80 C for 4 hours and crushed in a mill, obtaining granules with a size of 0.3-0.4 mm By spraying "in a suspended layer" at a temperature of 50 C from the 10% acetone solution of a vinylpyrrolidone-butyl methacrylate copolymer (nitrogen content 5.7% by weight), an outer layer of 0.12-0.15 mm thick is formed. Microcontainers are used for applying to the wound surface of soft tissues adjacent to the removed kidney, which had a malignant tumor after removal of the kidney. The sorption capacity of microcontainers is 110-120%. The duration of local antitumor action is 18-20 days. The time of complete destruction of the sorbent is 20 days.

Example No. 2.

20 g of a copolymer of vinylpyrrolidone with butyl methacrylate (nitrogen content 4.7% by weight) (65%) and 10.8 g of ambene are dissolved in 40 g of ethanol and, after the copolymer is completely dissolved, 10.8 g of metatrixate are added with stirring and the suspension is poured onto a polymer the substrate and dried at a temperature of 75 C for 8 hours. The resulting film is removed from the substrate and ground in a mill to obtain sorbent granules with a size of 0.05-0.08 mm. The granules are loaded into liquid paraffin and a 4% solution of PPB-1 copolymer is added to the suspension with stirring. The method of removing acetone while passing nitrogen and a temperature of 50 C on the surface of the granules form the outer layer with a thickness of 0.05-0.07 mm Microcontainers are used to apply to the surface of the lung tissue after resection of part of the lung. Sorption capacity of the sorbent is 100-110%. The duration of local antitumor action is 8-10 days. The time of complete destruction of the sorbent is 14 days.

Example No. 3.

20 g of a copolymer of vinylpyrrolidone with butyl methacrylate grade PPB-1 (90%) and dissolved in 45 g of ethyl alcohol, 2.22 g (10%) of chi splatin are introduced while moving, the resulting suspension is poured onto a polymer substrate, dried in vacuum at a temperature of 60 C. The resulting film is removed from the substrate and ground in a mill to obtain sorbent granules with a size of 1.0-1.5 mm. The granules are placed in liquid paraffin and 16% by weight are added to the suspension with stirring. a solution of copolymer PPB-1 in ethanol. The method of removal of ethyl alcohol while passing nitrogen and a temperature of 70 C on the surface of the granules form an outer layer with a thickness of 0.17-0.20 mm Microcontainers are used to apply to the surface of the liver after removing part of it that is affected by a malignant tumor. Sorption ability is 130-150%. The duration of local antitumor action is 38-40 days. The time of complete destruction of the sorbent is 40 days.

The advantages of using the proposed utility model in comparison with the prototype are shown in table No. 1.

Table number 1. Comparative results of the use of sorbents for the prototype and for
proposed model. No. Parameter Name Parameter value According to the prototype According to the proposed utility model by examples one 2 3 one Dates of complete resorption in the body, day 0.15-0.25 twenty fourteen 40 2 Sorption ability in relation to exudates,% 0 110-120 100-110 130-150 3 The number of injections of the antitumor drug during the course of treatment 4-16 one one one four The duration of local antitumor activity, day one 18-20 8-10 38-40 5 The total dose of the antitumor substance, mg 2500-3500 200 350 one hundred

Claims (1)

A polymer microcontainer containing a medicinal substance, characterized in that it consists of two parts: a central part made in the form of granules with a described circle diameter of 0.05-1.5 mm, made from a copolymer of vinylpyrrolidone with butyl methacrylate and an antitumor substance in the following ratio constituent parts, wt.%: vinylpyrrolidone copolymer with butyl methacrylate 65.0-90.0 antitumor substance 10.0-35.0 and an outer shell of a vinylpyrrolidone copolymer with butyl methacrylate with a thickness of 0.05 to 0.2 mm.