RU2771015C2 - Pharmaceutical composition in the form of an ointment for the treatment of hemorrhoids - Google Patents

Abstract

FIELD: pharmaceutical industry.SUBSTANCE: invention relates to the pharmaceutical industry, in particular to a pharmaceutical composition in the form of an ointment for the treatment of hemorrhoids. The presented pharmaceutical composition contains, wt.%: muscone 0.9, pearl 0.8, amber 0.3, calamine 10.7, artificial bezoar 1.1, borneol 3.8, dry or thick licorice extract 1.0, lanolin 4.0, lecithin 2.0, petrolatum 74.4, sodium tetraborate 1.0.EFFECT: claimed pharmaceutical composition provides the treatment of hemorrhoids and related diseases due to the pharmacological synergy of all the ingredients used in the composition of the claimed agent in the claimed amount.1 cl

Description

The invention relates to the field of pharmaceutical industry, in particular to pharmaceutical compositions in the form of ointments for the treatment of hemorrhoids.

Hemorrhoids is a common disease and is a pathological increase in blood vessels (hemorrhoids) of the anal canal and lower rectum. In recent decades, the risk of hemorrhoids has increased due to a change in the lifestyle of a modern person, as people began to move less, and also began to consume predominantly processed foods.

For the treatment of hemorrhoids, various pharmaceutical compositions are used in the form of various dosage forms, for example, ointments (Vidal's electronic reference book of 2010, update date: 2020. 01. 15, URL: https://www.vidal.ru/encvclopedia/gastroenterologiva/gemorroy) .

Known ointment for the treatment of hemorrhoids "Aurobin", which includes the hormone prednisone. With prolonged local use of corticosteroids or with extensive application to the skin, suppression of adrenal function may develop. For this reason, it can be used only after the recommendation of a doctor. The drug is dispensed by prescription (Electronic edition of the Vidal guide 2020, update date: 2020.04.29 URL: https://www.vidal.ru/drugs/aurobin).

Known ointment for the treatment of hemorrhoids "Posterizan". Phenol is used as a preservative in the preparation, therefore, allergic reactions are possible in patients with hypersensitivity to this component (Register of Medicines of Russia, URL https://www.rlsnet.ru/tn index id 2641.htm, Electronic edition of the Vidal reference book 2010 , update date: 2020.01.15, URL: https://www.vidal.ru/drugs/posterisan 681).

Known ointment for the treatment of hemorrhoids "Proctosedil", which includes not only an antibiotic, but also the active substance heparin. The use of the ointment in high doses and / or for a long time there is a risk of systemic side effects associated with hydrocortisone, such as discomfort in the rectum, burning in the rectum, dryness of the rectal mucosa. In addition, this ointment should be used with caution in patients with arterial hypertension, chronic heart failure (Electronic edition of the Vidal 2015 guide, updated on 2019.01.11, URL: https://zdravcity.ru/upload/vi dal/PDF / PROCTOSEDYL 41217.pdf).

Known ointment for the treatment of hemorrhoids "Relief", containing as an active substance phenylephrine hydrochloride, as auxiliary substances: mineral oil, petroleum jelly, methyl parahydroxybenzoate, propyl parahydroxybenzoate, benzoic acid, corn oil, glycerol, lanolin alcohol, paraffin, purified water, thyme oil herbs, vitamin E (alpha-tocopherol acetate), white beeswax. However, there are significant contraindications when using this ointment: thromboembolic disease, arterial hypertension, hyperthyroidism, diabetes mellitus, urinary retention (prostatic hypertrophy), etc. (Register of Medicines of Russia, URL https://www.rlsnet.ru/tn index id 7683.htm, Electronic edition of the Vidal reference book, URL https://www.vidal.ru/drugs/relief 1500).

An ointment for the treatment of hemorrhoids is known according to the patent for invention No. 2124362, which contains an extract of celandine herb, a vaseline-lanolin base and an anesthetic, however, from a pharmacological point of view, this ointment is mainly a symptomatic agent aimed at eliminating pain, without a pronounced specific action.

Known ointment for the treatment of hemorrhoids and method of preparation according to the patent for the invention CN No. 1209118C "Ointment for the treatment of hemorrhoids and method of preparation", the copyright holder Mainlong Pharmaceutical Group, Ltd. The pharmaceutical composition in the form of an ointment is claimed to have the following composition: vaseline, borneol, pearl, calamine, borax, amber, bezoar, dimethyl sulfoxide (DMSO), lanolin, muscone. The ointment is obtained in the following way: A. Grind pearls and amber, sift through a 100-120 mesh sieve; V. Muscon, bezoar, borax, borneol and 1/5 calamine mix with pearls and amber, sift through a 100-120 mesh sieve; C. Mix the powder from point B. with 4/5 of the calamine powder; D. Grind the powder in an ultrafine mill; E. Heat vaseline to 80-100°C, sterilize at 115-120°C, cool to 70-80°C; F. Lanolin sterilized at 115-120°C; G. Heat DMSO to 55-65°C; H. Place Vaseline in a container, filter and add the mixture, add borneol, DMSO and lanolin, then add the mixture from point D., and mix everything. The resulting ointment is a complex preparation with a local astringent, decongestant, antiseptic, analgesic, hemostatic effect. However, the presence of dimethyl sulfoxide (DMSO) in the composition of the ointment, which has a slightly toxic effect, worsens the safety profile of the ointment, as it increases the risk of side effects with prolonged and regular use. Considering that hemorrhoids is a chronic disease with a tendency to frequent relapses, the safety requirements for the drugs used for its treatment are decisive when choosing a pharmaceutical composition.

The closest in technical essence and the achieved result is Bezornil ointment for rectal and external use, which is selected as a prototype. The owner of the registration certificate No. PYSH20SH01 dated 09/26/11 is MAINLUN Joint Stock Pharmaceutical Enterprise, 3rd Pharmaceutical Factory (China) (Electronic edition of the Vidal reference book 2010, updated date: 2020.01.15, URL: https://www.vidal.ru/ drugs/bezornvl 30019). The ointment is obtained by the method described in the patent for the invention CN No. 1209118C "Ointment for the treatment of hemorrhoids and method of preparation". The prototype ointment contains artificial musk (muscone), pearls, artificial bezoar, amber, borneol, zinc carbonate (calamine), lanolin, vaseline, sodium tetraborate. The ointment is characterized by a local astringent, decongestant, antiseptic, analgesic, hemostatic effect. In some cases, allergic reactions are known in the form of hyperemia and exfoliation of the skin, urticaria and rashes (https://prigemorroe.ru/preparatv/bezornil.html). At the same time, Bezornil ointment (prototype) does not contain a component with a specific local immunomodulatory and antiallergic effect, which is extremely important in the treatment of hemorrhoids, since this disease often has concomitant eczematous dermatitis, an inflammatory skin disease of the perianal region. In addition, Bezornil ointment has a pronounced oily texture, has poor absorption, stains clothes, so it is advisable to use it only internally (rectally). To do this, the ointment is equipped with special caps that allow you to enter the ointment into the anus, thereby reducing the likelihood of contamination of linen. All this makes it difficult to use it for external treatment of cracks, itching of the anus and perineum, which are characteristic of acute and chronic hemorrhoids, as well as hemorrhoids in the postpartum period.

The problem to be solved by this invention is the expansion of the arsenal of effective and easy-to-use pharmaceutical compositions in the form of domestically produced ointments for the treatment of hemorrhoids and associated diseases.

The technical result of the invention is the treatment of hemorrhoids and concomitant diseases due to the pharmacological synergy of all ingredients used in the composition of the claimed agent in the claimed amount. The technical result is achieved by the fact that a pharmaceutical composition is presented in the form of an ointment for the treatment of hemorrhoids, containing artificial musk (muscone), pearls , artificial bezoar, amber, borneol, zinc carbonate (calamine), lanolin, petroleum jelly, sodium tetraborate, licorice extract, lecithin, taken in the following ratio, wt.%:

Muscon 0.9 Pearl 0.8 Amber 0.3 Calamine 10.7 artificial bezoar 1.1 Borneol 3.8 Licorice extract dry or thick 1.0 Lanolin 4.0 Lecithin 2.0 Petrolatum 74.4 Sodium tetraborate 1.0

The conducted patent information search showed that individual components of the ointment or their combinations are found in known therapeutic ointments of a similar purpose, however, drugs in the form of an ointment for the treatment of hemorrhoids in the proposed combination of ingredients and their ratio in the composition of the claimed ointment were not identified. The proposed pharmaceutical composition of the ointment for the treatment of hemorrhoids differs from the prior art in that it contains additional components in the form of licorice root extract, lecithin.

As noted above, the prototype ointment does not contain a component with a pronounced local immunomodulatory effect. At the same time, it is known that local inflammation or erosive phenomena on the skin or mucous membrane is accompanied by the risk of a secondary infection of a microbial, fungal or viral nature.

The biologically active components of licorice have a proven local immunomodulatory effect, which makes it possible to overcome the above phenomena in patients with hemorrhoids ((https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175350/, ttps://www.ncbi. nlm.nih.gov/pmc/articles/PMC5816298/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168306/ https://www.ncbi.nlm.nih.gov/pmc/articles /PMC7167813/pdf/PTR-22-709.pdf.

The active components of licorice extract, primarily glycyrrhizic acid and its derivatives, have a proven corticosteroid-like effect, manifested in anti-allergic and anti-inflammatory effects ((Electronic edition of the Vidal guide 2011, updated date: 2019.12.19 URL: https://www .vidal.ru/drugs/glycyrrhizae_radices 16584. Corticosteroids are an ingredient in many hemorrhoid medications.

The patented product is positioned as a drug of wide pharmacological action using components of natural origin, so its use is possible not only in the treatment of hemorrhoids (hemorrhoids), but also in the treatment of fissures, eczema of the anus, perineum and other phenomena that are concomitant with hemorrhoids. The inclusion of licorice extract in the composition of the patented product makes it possible to enhance the anti-allergic and anti-inflammatory effect of the drug without the addition of synthetic components.

As already noted, the above ointment - the prototype has a greasy texture, poorly absorbed. The addition of lecithin will make it possible to achieve a more pasty-powdery texture in the new product, improve absorption, and lengthen the exposure time at the application site.

The addition of licorice extract enriches and expands the pharmacological action of the ointment, namely, it enhances the immunomodulatory, regenerating, antiseptic, anti-inflammatory effect on damaged skin and mucous surfaces.

The introduction of lecithin as a surfactant and an emulsifier allows the patented product to become more structurally homogeneous, elastic and plastic compared to the prototype ointment.

Thus, we can talk not just about the summation of the types of action, but also about the synergistic effect of mutual enhancement of the action of all components that make up the patented product.

The causal relationship between the set of essential features and the technical result provided by the invention is that the use of a composition of artificial musk (muscone), pearls, artificial bezoar, amber, zinc carbonate (calamine), lanolin, vaseline, sodium tetraborate with the addition of an extract licorice root, lecithin in the proposed quantitative range makes it possible to obtain a new pharmaceutical composition in the form of an ointment with extended pharmacological action.

The given quantitative indicators of the components that make up the ointment were determined experimentally, are optimal and provide the maximum effectiveness of the ointment and allow you to achieve the claimed technical result.

A pharmaceutical composition in the form of an ointment for the treatment of hemorrhoids is prepared as follows.

1. Grind pearls, amber, borax, calamine, licorice root extract and sift through a 120-150 mesh sieve;

2. Mix the powders;

3. The resulting powder is ground in an ultrafine mill (300 mesh);

4. Sterilize Vaseline at 115-120°C, strain, cool;

5. Sterilize lanolin at 115-120°C, strain, cool;

6. Vaseline and lanolin mix;

7. Add borneol to the vaseline-lanolin mixture;

8. Filter the hot mixture (120-150 mesh);

9. Add the following components to the powder from item 3: muscone, bezoar, lecithin, mix until smooth;

10. The resulting ointment is loaded into tubes.

Below are examples of the application of the claimed pharmaceutical composition.

Patient VD, male, 55 years old, employee of the personnel service. History: Bleeding after bowel movements, slight pain and swelling for several months. Research: plexus of nodes at an angle of 11 degrees, the external node is bleeding, the nodes were lubricated with the claimed composition, a week later the bleeding stopped, the pain subsided, the swelling subsided, the nodes disappeared. Result: Effective.

Patient Ya.F., female, 18 years old, student. Anamnesis: Bleeding after defecation for 5-7 days, pain in the part of the anus, significant discharge time. Examination: external node at an angle of 6 degrees. The surface is red, fresh cracks. Lubrication treatment with the claimed composition. After 7 days, a re-examination: the cracks have practically healed, there is no pain, the bleeding has stopped. On the 11th day of application of the claimed composition: the cracks were completely healed. Treatment: Complete disappearance of signs of the disease within 5 days. Result: Effective.

Thus, the proposed composition has a number of significant features, in particular, it has a more pronounced anti-inflammatory, anti-allergic, wound-healing, immunostimulating effect compared to the prototype ointment, a high level of structure (homogeneity, plasticity, elasticity) and, as a result, better absorption, which allows the use ointment for the treatment of concomitant symptoms of hemorrhoids, such as fissures, eczema, and other wounds of the anus and perineum.

All this makes it possible to use the claimed product in a wide clinical practice for the treatment of hemorrhoids and related diseases, as well as the production of ointment in Russia, which is most relevant in the context of import substitution and a pandemic.

Claims (2)

Pharmaceutical composition in the form of an ointment for the treatment of hemorrhoids, containing artificial musk (muscone), pearls, artificial bezoar, amber, borneol, calamine (zinc carbonate), lanolin, vaseline, sodium tetraborate, licorice extract, lecithin, taken in the following ratio of components, wt .%: Muscon 0.9 Pearl 0.8 Amber 0.3 Calamine 10.7 artificial bezoar 1.1 Borneol 3.8 Licorice extract dry or thick 1.0 Lanolin 4.0 Lecithin 2.0 Petrolatum 74.4 Sodium tetraborate 1.0