PHARMACOLOGICAL COMPOSITION FOR TREATING PROCTOLOGICAL DISEASES (VARIANTS)

Abstract

This invention relates to medicine and more particularly to pharmacological compositions for treating proctologic diseases. The pharmacological composition comprises 3.3-7.5 wt % methyluracil, 0.13-0.3 wt % nifedipine, 1.3-5 wt % lidocaine, a pharmacologically acceptable carrier—rest. The pharmacological composition could be in the form of gel, or ointment, or cream, or suppositories, or suspended gel, or lotion, or emulsion.

Claims

1. A pharmacological composition for treating proctologic diseases, characterized in that it comprises 3.3-7.5 wt % methyluracil, 0.13-0.3 wt % nifedipine, 1.3-5 wt % lidocaine, a pharmacologically acceptable carrier—rest.

2. The pharmacological composition according to claim 1, characterized in that it could be in the form of gel, or ointment, or cream, or suppositories, or suspended gel, or lotion, or emulsion.

3. A pharmacological composition for treating proctologic diseases, characterized in that it consists of 5 wt % methyluracil, 0.2 wt % nifedipine, 2-5 wt % lidocaine, a pharmacologically acceptable carrier—rest.

4. The pharmacological composition according to claim 3, characterized in that it could be in the form of gel, or ointment, or cream, or suppositories, or suspended gel, or lotion, or emulsion.

Description

EMBODIMENT OF THE INVENTION

[0029] Embodiments of the invention are illustrated by the following examples:

Example 1

[0030] Preparation of gel comprising 3.3 wt % methyluracil, 0.13 wt % nifedipine, 1.3 wt % lidocaine.

[0031] Step-by-step procedure for preparing 1000 g of gel is given below.

[0032] 1. The gel is prepared by mixing 33 grams of methyluracil, 13 grams of lidocaine, two grams of Carbopol (a mixture of carbomers), one gram of ethylenediaminetetraacetic acid (EDTA), two grams of Nipagin (propylparaben, antimicrobial additive, preservative) and 18.5 grams of triethanolamine with addition of water to total weight of 850 grams.

[0033] 2. 1.3 grams of nifedipine were mixed with 10 ml of 96% ethanol. 40 grams of polyethylene glycol-400 were added to the obtained solution. After thorough mixing, propylene glycol was added to the obtained solution to a total weight of 150 grams.

[0034] 3. The nifedipine solution was added with thorough mixing to the suspended gel comprising methyluracil and lidocaine to form a pharmaceutical gel composition.

[0035] Test results of using a gel comprising 3.3 wt % methyluracil, 0.13 wt % nifedipine, 1.3 wt % lidocaine in patients suffering from hemorrhoids and anal fissures.

[0036] 100 tubes containing 50 grams of the gel prepared according to Example 1 were distributed to patients suffering from hemorrhoids and anal fissures. 100 patients applied the gel 2-3 times daily for 21 to 45 days. As a result of the gel application, recovery was observed in all cases (ease from pain, cessation of bleeding, elimination or significant reduction of hemorrhoids edema, healing of anal fissures). No side effects were observed at the gel application. The majority of patients (approximately 58%) recover within 21 to 28 days, while the remaining 42% of patients recover within 29 to 45 days. At the same time, the majority of patients (about 60%) noted attenuation of pain sensations already within the first three days of the gel application.

Example 2

[0037] Preparation of a gel comprising 5 wt % methyluracil, 0.2 wt % nifedipine, 2 wt % lidocaine.

[0038] Step-by-step procedure for preparing 1000 g of gel is given below.

[0039] 1. The gel is prepared by mixing 50 grams of methyluracil, 20 grams of lidocaine, two grams of Carbopol (a mixture of carbomers), one gram of ethylenediaminetetraacetic acid (EDTA), two grams of Nipagin (propylparaben, antimicrobial additive, preservative) and 18.5 grams of triethanolamine with addition of water to total weight of 850 grams.

[0040] 2. 2 grams of nifedipine were mixed with 10 ml of 96% ethanol. 40 grams of polyethylene glycol-400 were added to the obtained solution. Thorough mixing the solution. Propylene glycol was added to the obtained solution to a total weight of 150 grams.

[0041] 3. The nifedipine solution was added with thorough mixing to the suspended gel comprising methyluracil and lidocaine to form a pharmaceutical gel composition.

[0042] Test results of using a gel comprising 5 wt % methyluracil, 0.2 wt % nifedipine and 2 wt % lidocaine in patients suffering from hemorrhoids and anal fissures.

[0043] 100 tubes containing 50 grams of the gel prepared according to Example 2 were distributed to patients suffering from hemorrhoids and anal fissures. 100 patients applied the gel 2-3 times daily for 21 to 45 days. As a result of the gel application, recovery was observed in all cases (ease from pain, cessation of bleeding, elimination or significant reduction of hemorrhoids edema, healing of anal fissures). No side effects were observed at the gel application. When applying the gel prepared in accordance with example 2, the majority of patients (approximately 66%) recover within 21 to 28 days, while the remaining 34% of patients recover within 29 to 45 days. At the same time, the majority of patients (about 76%) noted attenuation of pain sensations within the first three days of the gel application.

Example 3

[0044] Preparation of gel comprising 7.5 wt % methyluracil, 0.3 wt % nifedipine, 5 wt % lidocaine.

[0045] Step-by-step procedure for preparing 1000 g of gel is given below.

[0046] 1. the gel is prepared by mixing 75 grams of methyluracil, 30 grams of lidocaine, two grams of Carbopol (a mixture of carbomers), one gram of ethylenediaminetetraacetic acid (EDTA), two grams of Nipagin (propylparaben, antimicrobial additive, preservative) and 18.5 grams of triethanolamine with addition of water to total weight of 850 grams.

[0047] 2. 3 grams of nifedipine were mixed with 10 ml of 96% ethanol. 40 grams of polyethylene glycol-400 were added to the obtained solution. After thorough mixing, propylene glycol was added to the obtained solution to a total weight of 150 grams.

[0048] 3. The nifedipine solution was added with thorough mixing to the suspended gel comprising methyluracil and lidocaine to form a pharmaceutical gel composition.

[0049] Test results of using a gel comprising 7.5 wt % methyluracil, 0.3 wt % nifedipine and 5 wt % lidocaine in patients suffering from hemorrhoids and anal fissures.

[0050] 100 tubes containing 50 grams of the gel prepared according to Example 3 were distributed to patients suffering from hemorrhoids and anal fissures. 100 patients applied the gel 2-3 times daily for 21 to 45 days. As a result of the gel application, recovery was observed in all cases (ease from pain, cessation of bleeding, elimination or significant reduction of hemorrhoids edema, healing of anal fissures). No side effects were observed at the gel application. When applying the gel prepared in accordance with example 3, the majority of patients (approximately 64%) recover within 21 to 28 days, while the remaining 36% of patients recover within 29 to 45 days. Moreover, approximately 81% of patients noted attenuation of pain sensations within the first three days of the gel application.

Comparative Example 4

[0051] A gel was prepared according to the closest analogue (RU 2592366) comprising 3.3 wt % methyluracil, 0.13 wt isosorbide dinitrate, 0.13 wt nifedipine, 1.3 wt lidocaine.

[0052] Step-by-step procedure for preparing 1000 g of gel is given below.

[0053] 1. The gel is prepared by mixing 33 grams of methyluracil, 13 grams of lidocaine, two grams of Carbopol (a mixture of carbomers), one gram of ethylenediaminetetraacetic acid (EDTA), two grams of Nipagin (propylparaben, antimicrobial additive, preservative) and 18.5 grams of triethanolamine with addition of water to total weight of 850 grams.

[0054] 2. 1.3 grams of nifedipine were mixed with 10 ml of 96% ethanol. 40 grams of polyethylene glycol-400 were added to the resulting solution. After thorough mixing, propylene glycol was added to the resulting solution to a total weight of 135 grams.

[0055] 3. 10 grams of dimethylsulfoxide (DMSO) were added to five grams of a mixture comprising 26 wt % (1.3 grams) isosorbide dinitrate and 74 wt % (3.7 grams) lactose. The mixture was stirred until a clear solution was obtained.

[0056] 4. Isosorbide dinitrate solution was added to the nifedipine solution.

[0057] 5. The combined solution of isosorbide dinitrate and nifedipine was added with thorough mixing to the suspended gel comprising methyluracil and lidocaine to form a pharmaceutical gel composition.

[0058] Test results of using a gel comprising 3.3 wt % methyluracil, 0.13 wt % isosorbide dinitrate, 0.13 wt % nifedipine, 1.3 wt % lidocaine in patients suffering from hemorrhoids and anal fissures.

[0059] 100 tubes containing 50 grams of the gel prepared according to Example 1 were distributed to patients suffering from hemorrhoids and anal fissures. 100 patients applied the gel 2-3 times daily for 21 to 45 days. As a result of the gel application, recovery was observed in all cases (ease from pain, cessation of bleeding, elimination or significant reduction of hemorrhoids edema, healing of anal fissures). No side effects were observed at the gel application. The majority of patients (approximately 61%) recover within 21 to 28 days, while the remaining 39% of patients recover within 29 to 45 days. Moreover, only 59% of patients noted attenuation of pain sensations within the first three days of the gel application.

[0060] Thus, preparation of the gel according to the proposed formulation, as compared to the closest analogue, enables to simplify the medication preparation procedure, reducing it by two operations and, accordingly, to reduce the composition preparation time, and also to reduce its cost.

[0061] Moreover, use of the proposed composition, as compared to the closest analogue, has only a slightly reduced objective observed therapeutic effect, which, nevertheless, significantly exceeds the effect of the other known medications.

[0062] Besides, when using this medication, patients noted a faster and more significant attenuation of pain sensations, which also has a positive effect on general well-being and contributes to a faster recovery.

[0063] When using a comparative composition not comprising methyluracil, distribution of recovered patients by treatment time was of dissimilar nature. Thus, the majority of patients (approximately 59%), among the patients recovered up to 45 days, 60% of patients used the comparative composition not comprising methyluracil, recovered over a longer period of 29 to 45 days. With an increase in duration of treatment with a comparative composition over 45 days, the total percentage of patients with complete recovery increases even more. Moreover, only 47% of patients noted attenuation of pain sensations within the first 3 days of using the medication.

[0064] Based on the test results, the optimal ratio of the components forming the composition has been determined. According to the studies, when decreasing or increasing the concentration of active components from the claimed limits, no enhancement of the composition therapeutic properties occurs. That is, any deviations from the optimal ratio of the components do not allow to obtain the desired therapeutic effect. Moreover, the qualitative composition of the claimed composition is selected empirically and absence of any ingredient in its composition does not allow to achieve the result obtained with the use of the claimed composition.

[0065] Thus, use of a complex pharmacological composition based on 3.3-7.5 wt % methyluracil, 0.13-0.3 wt % nifedipine and 1.3-5 wt % lidocaine, in patients suffering from hemorrhoids and anal fissures, has enabled to enhance and accelerate achieving the therapeutic effect, as compared to the composition not comprising methyluracil.

[0066] Other interpretations and variations of the present invention are possible, which do not contradict the claims in terms of preparing a pharmaceutical composition, type of the pharmaceutical composition, method and scope of its application. In particular, based on the proposed composition, including 3.3-7.5 wt % methyluracil, 0.13-0.3 wt % nifedipine and 1.3-5 wt local anesthetic there could be prepared ointments, suppositories, creams, lotions, suspensions that can be applied locally for treating chronic hemorrhoids, acute hemorrhoidal manifestations (all stages), anal fissures, traumatic injuries of anus and rectum, sphincter, post-operative care of persons completed a treatment of hemorrhoids, polyps, papillomas, condylomata by surgical methods, pathological changes of hemorrhoidal boluses, as anesthetic and relaxing agent for anorectal area, anal mucous membrane irritation, sphincter spasmolysis, in mono- and complex therapy of proctologic diseases, such as: proctitis, periproctitis, rectum cancer, anal cancer, proctosigmoiditis, anal fistulas, anal inflammatory processes, cryptitis, megacolon, rectal fibroma.