RU2601621C2 - Sodium deoxyribonucleate suppositories, rectal and vaginal - Google Patents

Abstract

FIELD: pharmaceutics.

SUBSTANCE: described is a pharmaceutical composition in form of a suppository, rectal or vaginal characterised by the fact that it contains as an active substance sodium salt of deoxyribonucleic acid and lipophilic base. Said base contains cocoa butter or cocoa butter alloys with paraffin or wax, or hydrogenated fat or vegetable and animal hydrogenated fats, or solid fat in the form of a mixture of lauric acid mono-, di- and triglycerides, or lanol, or alloys hydrogenated fats with wax or a solid paraffin at specified ratio. Also described is a method for preparing the composition.

EFFECT: invention provides high stability during storage at maintaining sufficient bioavailability for effective action.

3 cl, 3 tbl, 5 ex

Description

The invention relates to the field of chemical pharmaceutical industry and medicine.

Existing traditional methods of treating infections using etiotropic antibacterial and chemotherapeutic drugs are often ineffective or have a short-term effect, especially in the treatment of chronic relapsing forms of the disease. This is due to several reasons: a change in the sensitivity and resistance of pathogens to the used antibacterial drugs, the occurrence of side effects of the therapy (allergic reactions, dysbiosis, immunosuppressive effect, etc.), developing the so-called "immunological deficiency" syndrome, which can lead to prolonged persistence of the pathogen, to frequent relapses of the disease, and to the possibility of subsequent infections with infectious agents of a different nature, The restoration of the immune status and normalization of microbiocenosis occurs in insufficient volume and at a pace or does not occur at all.

Thus, it is advisable to include immunotropic drugs in the complex anti-inflammatory or anti-infective therapy that promote the stimulation of non-specific resistance factors and are endowed with immunocorrective properties.

One of the currently effective immunotropic drugs is Derinat (sodium deoxyribonucleate). Derinat has an immunomodulatory, anti-inflammatory, reparative, regenerative effect.

The drug activates antiviral, antifungal and antimicrobial immunity at the cellular and humoral levels. Regulates hematopoiesis, normalizing the number of leukocytes, granulocytes, phagocytes, lymphocytes and platelets. Corrects the state of tissues and organs with dystrophy of vascular origin, exhibits weak anticoagulant properties. In patients with chronic ischemic disease of the lower extremities (including those with diabetes mellitus), it increases exercise tolerance when walking, reduces pain in the calf muscles, and prevents the development of a feeling of coldness and coldness of the feet. Improves blood circulation of the lower extremities, promotes the healing of gangrenous trophic ulcers, the appearance of a pulse on the peripheral arteries. It accelerates the rejection of necrotic masses (for example, on the phalanges of the fingers), which sometimes avoids surgical intervention. In patients with coronary artery disease improves myocardial contractility, improves microcirculation in the heart muscle, increases exercise tolerance and shortens recovery time. It stimulates the reparative processes in gastric and duodenal ulcers, restores the structure of the mucous membrane, and inhibits the growth of Helicobacter pylori. Facilitates engraftment of autografts during skin and tympanic membrane transplantation.

Sodium deoxyribonucleate is released in the form of solutions for injection (http://medi.ru/doc/x0056.htm). The solution for injection is injected intramuscularly, slowly, over 1-2 minutes, 5 ml in 24-72 hours; with peptic ulcer of the stomach and duodenum - 5 injections with an interval of 48 hours; for oncological diseases 1 time in 2-3 days (3-10 injections per course); with gynecological and andrological diseases - 1 injection every other day (10 injections in total). However, with the introduction of a possible short-term increase in body temperature.

Solutions for external use are also currently available (http://www.abc-gid.ru/drugs/reestr/show/100233/). The solution for external use has an effect on obliterating diseases of the lower extremities, defects in the mucous membrane of the oral cavity, nose, and vagina. The solution is used for the prevention of acute respiratory viral infections - 2-3 drops 2-4 times a day in each nasal passage, treatment of acute respiratory viral infections - 3-5 drops 1 time / hour; with lesions of the oral mucosa - rinse 4-6 times a day; in chronic inflammatory diseases and lesions of the mucous membrane in gynecological practice - intravaginal administration of tampons moistened with a solution; post-radiation necrosis of the skin and mucous membranes, long-term non-healing wounds, burns, frostbite, trophic ulcers - application dressings 3-4 times a day with simultaneous instillation into the nose.

The prior art describes a therapeutic and prophylactic agent based on derinate in the form of a suppository for the treatment of urogenital chlamydia, cytomegalovirus, herpes simplex, Helicobacter pylori (RU 2429854 C2, publ. 09.27.2011). According to the described method for preparing suppositories, PEO 1500 and PEO 400 are melted in a 9: 1 ratio, the calculated amount of sodium chloride preservative is added to the melt, and then the calculated amount of sodium deoxyribonucleate is added with stirring. The molten mass is molded and Derinat suppositories weighing 1.3-2.5 g are obtained. The obtained suppositories provide high bioavailability and long-term exposure to the active agent. This solution can be indicated as the closest analogue of the prototype.

The objective of the invention is the creation of rectal and vaginal suppositories, effective in a wide range of diseases of the genitourinary system and diseases of the pelvic organs that do not contain preservatives.

The problem is solved by a new therapeutic and prophylactic agent in the form of a suppository and a method for its preparation.

The product contains as its active substance the sodium salt of deoxyribonucleic acid and a lipophilic base, containing cocoa butter or cocoa butter alloys with paraffin or wax, or hydrogenated fat, or vegetable and animal hydrogenated fats, or solid fat in the form of a mixture of mono-, lauric acid di- and triglycerides, or lanol, or alloys of hydrogenated fats with wax or paraffin wax in the following ratio of components, mass. %:

deoxyribonucleic acid sodium salt 1.0-25.0 lipophilic basis rest

Preferably, in the case of a base choice in the form of alloys of cocoa butter with paraffin, the proportion of paraffin in the mixture with cocoa butter is 30-35% by weight.

The bases in the form of alloys of hydrogenated fats with paraffin are produced under the name butyrol. For example, the base may contain 40 parts of cocoa butter, 92.08 parts of pork fat, 5.21 parts of yellow wax, 6.68 parts of paraffin, 1.05 parts of glycerin. Butyrol base is currently being produced, which consists of 50% hydrogenated fats, 20% paraffin, 30% cocoa butter. You can also use an alloy of hydrogenated fats with 4% paraffin, etc.

Hydrogenated vegetable fats can be selected, for example, from hydrogenated cottonseed, sunflower, palm kernel, soybean, peanut or castor oil. Hydrogenated animal fats can, for example, be selected from pork, cow, lamb, cowhide or mixtures of salomas.

Lanol is a mixture of phthalic acid esters with high molecular weight alcohols of sperm whale fat. This is a solid homogeneous wax-like mass of white color with a peculiar smell. Melting point 36-37 ° C. Based on this substance, a suppository base of the following composition was developed: 60.0 g (80.0 g) of lanol; 20.0 g (10.0 g) of hydrogenated fat and 20.0 g (10.0 g) of paraffin.

The tool in the form of a suppository is obtained by placing the lipophilic base in a container equipped with a water jacket and a mixing device, where it is melted to a homogeneous mass at a temperature of 55-65 ° C with constant stirring, cooling to a temperature of 34-36 ° C, adding the active substance, homogenization with a colloid mill to a homogeneous state at a temperature of 40-42 ° C, cooling to a temperature of 34-36 ° C, followed by filling with a batcher of the obtained mixture of cells of the contour packaging, which are cooled to atnoy temperature in the chilling tunnel.

It is a known fact that in the case of hydrophilic bases, it is preferable to use hydrophilic bases in order to ensure high bioavailability of soluble active substances for suppositories and ointments. Unexpectedly, we found that sodium deoxyribonucleate in the form of hydrophilic suppositories is less stable during storage. Moreover, unwanted impurities are formed (Example of Table 3).

Eliminate this disadvantage has become possible with the help of the present invention.

The technical result of the invention is higher storage stability while maintaining bioavailability sufficient for the effective action.

The invention can be demonstrated by the following examples.

Example 1. Vaginal Suppositories 1.0

deoxyribonucleic acid sodium salt one% cacao butter 99%

Example 2. Vaginal Suppositories 1.0

deoxyribonucleic acid sodium salt 10% solid confectionery fat A 90%

Example 3. Rectal suppositories 1,5

deoxyribonucleic acid sodium salt 25% hydrogenated cow fat alloys and paraffin wax 75%

Example 4. Rectal Suppositories 1.0

deoxyribonucleic acid sodium salt 2.5% solid fat in the form of a mixture of mono-, di- and triglycerides lauric acid 97.5%

Example 5. Determination of the shelf life of the drug

“Sodium deoxyribonucleate”, rectal and vaginal suppositories, “accelerated aging” method

Party 8010414 - according to example 1 (table 1)

Lot 8020714 - according to example 4 (table 2)

Claims (3)

1. A pharmaceutical composition in the form of a suppository, rectal or vaginal, characterized in that it contains the deoxyribonucleic acid sodium salt and the lipophilic base as the active substance, comprising cocoa butter or cocoa butter alloys with paraffin or wax, or hydrogenated fat, or plant and animal hydrogenated fats, or solid fat in the form of a mixture of mono-, di- and triglycerides of lauric acid, or lanol, or alloys of hydrogenated fats with wax or hard paraffin otherwise in the following ratio of components, mass. %:
deoxyribonucleic acid sodium salt 1.0-25.0 lipophilic basis rest 2. The composition according to p. 1, characterized in that the base contains an alloy of cocoa butter with paraffin, where the proportion of paraffin in the mixture is 30-35% by weight. 3. A method of obtaining a pharmaceutical composition in the form of a suppository, rectal or vaginal according to claim 1 or 2, characterized in that the lipophilic base is melted in a container equipped with a water jacket and a mixing device to a homogeneous mass at a temperature of 55-65 ° C with constant stirring, cool to a temperature of 34-36 ° C, add the active substance, homogenize with a colloid mill to a homogeneous state at a temperature of 40-42 ° C, cool to a temperature of 34-36 ° C, followed by filling with a dispenser obtained by a mixture of contour packing cells, which are cooled to room temperature in a cooling tunnel.