Pharmaceutical composition for treatment of phimosis by topical using corticosteroid
FIELD: medicine, pharmacy.
SUBSTANCE: invention proposes a composition comprising one or more corticosteroids and/or hormonal steroids in the range from 0.025 to 5 wt.-% of the total composition mass and hyaluronidase in the amount from 25 to 4000 UTR per 1 g of the composition in the suitable carrier medium. The composition can comprise nonhormonal anti-inflammatory agents. The composition can be prepared in different medicinal formulations, such as gel, ointment, cream, aerosol with additives known from a person skilled in the art of the corresponding field. Betamethasone is the preferable corticosteroid. Ointment is the preferable medicinal formulation. Treatment by using corticosteroids in combination with hyaluronidase provides the improvement of state in 90% of patients, and after their treatment their prepuce can be drawn off easily.
EFFECT: improved medicinal properties of composition, enhanced effectiveness of treatment.
11 cl, 6 ex
The present invention features a pharmaceutical composition for the treatment of phimosis by topical application of a corticosteroid and/or hormonal steroids in combination with proteolytic diffusible enzyme in the presence or in the absence of non-hormonal anti-inflammatory agents. The scope of the present invention are the pharmaceutical industry, production of medicines on prescription and medical services.
Phimosis more often assumed than is found in reality. Often it turns out that this is actually the fusion of the foreskin and the glans penis, which is usually after a certain time resolve itself. The newborn boy's foreskin, usually fused with the glans penis and the exposure it so impossible, but over time, often within the first four years of life, this problem is solved naturally without interference. With the growth of the penis under the foreskin accumulate dead epithelial cells, resulting in the foreskin eventually separates from the glans penis. Even in countries where there is widespread rite of circumcision, the need for medical intervention occurs infrequently. Usually with the onset of puberty problems is solved by itself.
The incidence of phimosis in adolescents decreased from 8% to 1% (see Oster J. (Jay. Oster) "Further Fate of the Foreskin" ("the Further fate of the foreskin"), published in Arch. Dis. Child., 1968, 43:200-3. The number of cases of phimosis is small: only 0.4 per 1000 boys per year.
In the last few years was hotly debated topic of the circumcision. This procedure can be an effective way of dealing with phimosis, but it can lead to bleeding, stenosis of the urethra and tissue damage, resulting, in turn, may be the occurrence of fistula of urethra or the need for amputation of the glans penis. In 1981 in the United States was subjected to circumcision 80% of boys. In subsequent decades, this percentage had dropped.
Widely use the term "phimosis" is not clearly defined, in General, this term refers to the condition when no exposure of the glans penis by pulling the foreskin. According to the description of Rickwood (Rikwood), true phimosis is a condition when there is a whitish sclerotic ring, preventing the exposure of the glans penis. Research conducted in the UK show that doctors still have not learned to distinguish the fusion of the foreskin and the glans penis, which is a normal stud is her development, from phimosis, which is a pathology. This indicates that phimosis is accepted that that is the norm. The result is a lot of unnecessary operations circumcision.
Current status in the treatment of phimosis in article Dewan P.A., Tiv NS, Chieng B.S. (Pia. Devan, ACSI. Against and Bi. Asking) "Phimosis: Is Circumcision Necessary" ("Phimosis - circumcision"), published in the Journal of Paediatrics &Child Health, vol 32(4), August 1996, pages 284-289, which discusses the effectiveness of certain treatment of phimosis without surgery in the form of a circumcision.
In article Golubivic Z., Milanovic, D. and al. (The zed. Golubovich, Di. Milanovich and others) "The Conservative Treatment of Phimosis in Boys"("Conservative treatment of phimosis in boys"), published in the British journal of urology British Journal of Urology), volume 78(5), November 1996, pages 786-788, described successful treatment of boys over the age of three years, which was produced by local application of a cream containing 0.05% betamethasone compared with patients in respect of which produced local use only neutral cream (vaseline). In article Pless BECAUSE, Spjeldness N., Jorgensen, T.M. (Ti. Kay. Ples, EN. Speedness Ti. Em. Jorgensen) in the journal Ugeskrift for Laeger (Denmark), volume 161(47), page 6493-6495, 1999, described the treatment of the same type, that is, the local application of a cream with a content of 0.05% bet is metazone.
Another article, which describes the local application of a cream with a content of 0.05% betamethasone for the treatment of phimosis in boys - this article'orsola A., Caffaratti J., Garat J.M. (Hey. 'orsola, Jay. Caffaratti, Jay. Em. Garath) "Conservative Treatment of Phimosis in Children Using a Topic Steroid" ("Conservative treatment of phimosis in children using local application of steroid), published in Urology (Online), 56(2): 307-10, 01 August 2000.
The results of the treatment of phimosis by local application after hygienic procedures, creams containing 0.06% of betamethasone described in section S. Chu, K.C. Chen, Diau G.Y. (si. Si. CHU, Kay. Si. CHEN, JI. Wye. DAO) "Topical Steroid Treatment of Phimosis in Boys" ("Treatment of phimosis in boys by local application of steroid"), published in the Journal of urology, Journal of Urology, volume 162 (3-1), September 1999, pages 861-863. In article Monsour M.A., Rabinovitch H.H., Dean G.E. (Em. Hey. Mansur, H. H. Rabinovich, JI. I. Dean) "Medical Management of Phimosis in Children: Our Experience with Topical Steroids (Treatment of phimosis in children - Our experience local application of steroids"), published in the Journal of urology, Journal of Urology, volume 162(3-11), September 1999, pages 1162-1164, describes the successful treatment of boys with symptoms of phimosis by local application of a cream containing 0.05% betamethasone.
Among the drugs topical application for the treatment of phimosis are several types of steroids, for example in the form of creams, stermasi mometason in a concentration of 0.5%, hydrocortisone in concentrations of 1% and 2% and betamethasone in concentrations of 0.05%, koblasa at a concentration of 0.05%, the injection of the corticosteroid along with chorionic gonadotrophin (hCG) human, 0.05% betamethasone 0.1% strogen, 1% hydrocortisone, etc.
According to Wright (Wright) in the treatment of phimosis with betamethasone cream was a significant improvement in 88 of 111 patients (see Wright J.E., (Jay. I. Wright) "The treatment of Childhood Phimosis with Topical Steroid (Treatment of phimosis in children by local application of steroid"), published in the Journal surgery Australia and New Zealand (Aust. New Zeal. J. Surg.), 1994, volume 64, pages 327-330). According to Lindhagen (Lindhagen), in the treatment of phimosis with clobetasol propionate, a strong steroid, was achieved successful treatment in 70% of patients, however, this drug requires very careful handling (see Lindhagen So (So Lindhagen) "Topical Clobetasol Propionate Compared with Placebo in the Treatment of Unretractable Foreskin" ("the topical application of clobetasol propionate compared with placebo in the treatment of status potteryware foreskin"), published in the Journal European surgery (Eur. J. Surg.), 1996, volume 162, pages 968-972). According to Kirikos and others (Kirikos et al.) (see article Kirikos C.S., Beasley S.W. and Wood A.A. (si. Asterias, Establo. Beesley and Hey. Hey. Wood) "The Response of Phimosis to Local Steroid Application" ("the Effect of local application of steroi is and phimosis"), published in Pediatric Surgery, 1993, volume 8, pages 329-332) when using 2%hydrocortisone recovery was achieved in approximately 80% of patients. There were no reports of any negative actions of local or systemic (size of the absorption of the corticosteroid in this case is only 0.1% of the area of the body). While these studies have involved patients, whose average age was 6 years (boys from 2 to 15 years).
Conservative treatment is cheaper than surgery. Application betamethasone cream for four weeks with guaranteed success from 70% to 75% of cases cheaper than the circumcision (see Van Howe RS (Art. Espan-HOU "Cost-Effective Treatment of Phimosis" ("cost-effective treatment of phimosis"), published in Pediatrics, 1998, 102(4):E43).
To the extent permitted by state studies (see Atilla K., Dündaroz R., Odabas Ö., Öztürk H., R. and Akin Gökcay (K. K. Attila, R. Dundurs, O. Odabas, X. Ozturk, R. akin and Gucci) "A Nonsurgical Approach to the Treatment of Phimosis: Local Nonsteroidal Anti-Inflammatory Ointment Application" ("non-Surgical approach to the treatment of phimosis - local application esteroidales anti-inflammatory ointment"), published in the Journal of urology (J. of Urology), 1997, volume 158, pages 196-197) instead of corticosteroid as an alternative for cases when corticosteroids PR is tyopoytani, used nesteroidny anti-inflammatory agent. The result was a full or partial recovery of 75% of patients.
In reporting on the results of recent studies are described in more conservative approach to the treatment of phimosis, based on local application (in the area of the annulus) as steroids and nesteroidnykh anti-inflammatory agents. According to these reports, satisfactory results were achieved in 67%-95% of cases, while there were no harmful effects (see Marzaro m, G. Carmignola, Zoppellaro F., Schiavon G., Ferro, M., F. Fusaro, F. Bastian, G. Perrino (M Marzano, J. Carmagnola, F., Zappella, J. The Schiavone, M. Ferro, F., Fusaro, F. Bastasin, J. Perrino) "Fimosi: quando patologia and di interesse chirurgico?", published in Minerva Pediatr, 1997, vol 49(6), pages 245-248).
In article Lamprokopoulos E.A. (E.A. Lamprocapnos) "Use of betamethasone and hyaluronidase injections in the treatment of Peyronie''s disease" ("the Use of injections of betamethasone and hyaluronidase in the treatment of fibroplastic induration of the penis), published in the Scandinavian journal of urology and Nephrology (Scandinavian Journal of Urology and Nephrology, vol 34, No. 6, 2000, pages 355 to 360 above, XP 008011731, describes the treatment by injection, requiring the assistance of a third party, patients in addition to the primary disease phimosis different nature. Although fibroplasia induration of the penis, also called illness is through paroni, and phimosis refers to the penis, they are not considered similar diseases as they affect intercellular structures of various types. Phimosis is usually manifested in the impossibility or difficulty of exposure of the glans penis due to the narrowing of the foreskin, while fibroplasia induration of the penis characterized by fibrosis of the membrane tunica, exciting the cavernous body of the penis.
Phimosis is usually treated by circumcision (skin lesions covering the glans of the penis), which is removed mainly by surgery. Antiseptic treatment of phimosis involves topical application of corticosteroids, in particular according to the invention, the corticosteroid in combination with hyaluronidase.
Treatment fibroplastic induration of the penis usually involves surgical removal of the fibrous omotenashi. But there are reports on the medical treatment of this disease by injection into the region of the fibrous intercellular substance drugs, such as verapamil, collagenase, corticosteroids, or a combination of these means, for example, hyaluronidase, as described in the above mentioned article Iahamogoput (treatment by injection). It should be noted that fibroplasia induration of the penis h the school is in adulthood.
The aim of the invention is the development of a medicinal product having the properties of the treatment of phimosis, it should be possible to easy application of such drug by the patient to avoid the need for assistance, and taking into account that the majority of patients are young people or children (phimosis occurs most often in childhood or adolescence), to the use of the drug does not cause pain, which would be undesirable in long-term use, and the success of the treatment, therefore, would be achievable with great difficulty, besides, equally important, such treatment much more convenient in comparison with surgical intervention in the form of a circumcision.
Medical treatment of phimosis is different from medical treatment fibroplastic induration of the penis, as in the treatment of phimosis local application of the drug is in effect on the skin, while in the treatment fibroplastic induration of the penis injections are applied.
None of the above articles does not mention local application of steroids in combination with a diffusing agents to increase the effectiveness of treatment.
In order to avoid, when possible, painful surgery is circumcision, and thus, related bleeding (from 4% to 6% of cases), gastric ulcer and stenosis of the urethra (11%), infection (4% to 6% of cases), fistula, urethra, as well as accidentally deleting the wrong amount of skin that was required, which can cause new phimosis, the applicant has developed a new method of treatment involves topical application of a corticosteroid in combination with a diffusing enzyme, and that the treatment was effective. It was found that in the treatment of phimosis is the synergistic action of proteolytic enzymes and corticosteroids, and to achieve more promising results than in the case of the use of steroids or corticosteroids in the absence of such enzymes, such results include, in particular, the disappearance of the symptoms of phimosis for shorter periods of time.
The aim of the invention is to provide a new pharmaceutical composition for topical application for the treatment of phimosis, contributing to the separation of the foreskin from the glans penis by influencing the process of depolymerization of hyaluronic acid in connective tissue between the foreskin and the glans penis with the provision of treatment for a short time, with minimal side effects, effectively and inexpensively through the use of corticosteroids, in conjunction the Institute with hormonal steroids or without them, or in combination with nonsteroidal anti-inflammatory agents and proteolytic diffusing enzymes.
When using the pharmaceutical compositions according to the invention, provided is a cure phimosis 90% of patients at the age from 1 year to 30 years. Consequently, the patient, which in most cases is a child, not podvergatsya surgical injury and the associated risk. The skin of the foreskin remains intact, making it possible to avoid sensory and psychological discomfort.
This new treatment of phimosis by local drug application, which is used as a pharmaceutical composition for topical application, which is used corticosteroids and/or hormonal steroids in combination with proteolytic diffusing enzymes, in the presence or in the absence of non-hormonal anti-inflammatory agents, promotes the separation of the foreskin from the glans penis by influencing the process of depolymerization of hyaluronic acid in connective tissue between the foreskin and the glans penis, ensuring thus a non-trivial results.
When using the pharmaceutical compositions according to the invention, provided is a cure phimosis 90% of patients aged 1 year is about 30 years. Therefore, these patients, most of whom are children, are not subjected to surgical injury and the associated risk. The skin of the foreskin remains intact, making it possible to avoid sensory and psychological discomfort.
The aim of the proposed invention is a pharmaceutical composition suitable for the treatment of phimosis in children and adults using local application of corticosteroids in combination with diffusible enzyme without the necessity of circumcision (surgical treatment) with better than the local application steroidnykh or nonsteroidal anti-inflammatory agents, results (90%).
A combination of a corticosteroid with diffusing proteolytic enzymes promotes the separation of the foreskin from the glans penis by influencing the process of depolymerization of hyaluronic acid in connective tissue between the foreskin and the glans penis, ensuring thus the effect of local anesthesia and lysis of adhesions between the foreskin and the glans penis with better results than when using known treatments for phimosis.
Finally, it was found that the combination of topical application of corticosteroid with diffusing proteolytic enzymes more effectively than all there is existing methods of medical treatment of phimosis, and is an innovative therapy as adults and children alike.
The applicant developed a pharmaceutical composition for the treatment of phimosis with topical application of one or more corticosteroids, the content of which in the form of pharmaceutical compositions is from 0.025% to 5% by weight of the total pharmaceutical composition, in combination with non-hormonal anti-inflammatory agents, and one or more proteolytic diffusing enzymes in the amount of from about 25 UTR per gram up to 4000 UTR per gram in an environment suitable media, in different dosage forms, with additives, well known to the average expert in the field.
Suitable for use in the pharmaceutical compositions according to the invention, the corticosteroid can be selected, for example, from the following non-exhaustive list: betamethasone, hydrocortisone, cortisone acetate, balarat, butyrate or valerate hydrocortisone, clobetasol or clobetasol propionate, propionate, dipropionate, valerate, phosphate, acetate or other esters of betamethasone dipropionate of alometasone, desoximetasone, pialat of clocortolone, diacetate diflorasone, acetonide or flurandrenolide fluoqinolona, acetate, methylprednisolone, mometasone furoate, diacetate, amcinonide or fluocinonide of diflorasone, PR is peanut or desonide of halobetasol, acetonide triamcinolone, and mixtures of these substances.
In a preferred embodiment of the present invention, the contents of one or more corticosteroids from the family of betamethasone, such as, for example, 2-phenyl-1,2-benzeneseleninic-3(2H)-he and its derivatives, in the form of pharmaceutical compositions according to the invention is from about 0.5% to 3% by weight of the total pharmaceutical composition.
Betamethasone is a synthetic fluorinated corticosteroid having the form of crystalline powder white or almost white, insoluble in water, partially soluble in alcohol. It is used for applications of this type, in the preferred embodiment of the present invention is in the form of esters of such acids as Valerian (betamethasone valerate), propionic (propionate betamethasone), dipropionate (betamethasone dipropionate), phosphorus (phosphate betamethasone) or acetic acid (acetate betamethasone).
Of hormonal steroids in the form of pharmaceutical compositions according to the invention can be used, for example, testosterone.
Below is the structural molecular formula of betamethasone in his most suitable for use form - in the form of betamethasone valerate (Formula 1).
<> In an alternative embodiment of the present invention hormonal steroid may be used in combination with one or more non-hormonal anti-inflammatory agents that can be selected, for example, from the following non-exhaustive list: diclofenac, ibuprofen, naproxen, fenoprofen, tolmetin, sulindac, meclofenamate, Ketoprofen, piroxicam, flurbiprofen, oxaprozin.
The invention assumes the use in combination with the above components of one or more proteolytic diffusing enzymes, such as hyaluronidase, in the amount of from about 25 UTR per gram up to 4000 UTR per gram, in a preferred embodiment of the present invention is approximately in the range from 75 UTR per gram to 2000 UTR per gram.
Commercially available hyaluronidase is made from bovine or sheep testicles, or by means of biotechnological process, and released to the market in the form of a sterile or non-sterile iofile (yophl).
Under the action of hyaluronidase is the depolymerization of hyaluronic acid in the composition of the interstitial tissue, in particular skin and synovial fluid. Molecule of hyaluronic acid consists of a chain glucurono-N-acetylglucosamine blocks polymerized using stable glycosidic linkages, kotorayaraspolagaetsya under the action of hyaluronidase. The result is a decrease in viscosity, which facilitates the diffusion of substances through the tissue.
To accelerate the absorption and reduce the local strain of the tissue hyaluronidase may be added to the parenteral solution such as saliva, glucose, lactate or plasma. The suction in the field of traumatic edema or area in a state after surgery, or in the area of the hematoma can be accelerated by hyaluronidase infiltration and use of garrote (garrote). Similarly, it can be reduced inflammation caused by accidental shedding of irritating solutions.
The applicant developed mainly dosage forms topical application of the pharmaceutical composition according to the invention. It should be noted that the hyaluronidase quickly loses its effect in aqueous media, and this was the reason why the pharmaceutical composition according to the invention was developed primarily in the form of oil lipstick that does not contain water.
The development of the pharmaceutical composition is not straightforward. A professional in the industry who knows the drug, for example, in a form for injection containing a certain amount of the active component will not be able to produce a pharmaceutical composition that is effective is about and with good bioavailability could be applied in any dosage form for oral administration, or in the form of a lipstick, creams, etc.
However, there can be also excluded the possibility of developing a pharmaceutical composition intended for the preparation of a medicinal product for immediate use, for example, when freeze-dried form of pharmaceutical compositions according to the invention, immediately before the application is exposed to dilution water media.
Another addition to the stability of the enzyme, the advantage of the pharmaceutical compositions according to the invention, which is manifested in the case of its use in such a dosage form, as an oil lipstick, is that after applying it remains in contact with the intercellular structures foreskin over a longer period of time, as it cannot be easily washed away by urine, sweat or water while bathing.
One of the preferred embodiments of the present invention is a pharmaceutical composition for the treatment of phimosis by topical application, the active components are corticosteroids (one or more) family of betamethasone, the content of which is within approximately from 0.025% to 5% by weight of the total pharmaceutical composition, and proteolytic diffusing enzymes (one or more) family of hyaluronidase in to the a number of from about 25 UTR per gram up to 4000 UTR per gram in an environment suitable media, in various pharmaceutical forms, with additives, well known to the average expert in the field.
In one more specific variants of the pharmaceutical composition according to the invention, implemented in the dosage form of lipstick for the treatment of phimosis by topical application, the active components are corticosteroids (one or more) family of betamethasone, the content of which is within approximately from 0.025% to 5% by weight of the total pharmaceutical composition, and proteolytic diffusing enzymes (one or more) family of hyaluronidase in the amount of from about 25 UTR per gram up to 4000 UTR per gram in an environment suitable media, in different dosage forms, with additives, well known to the average expert in the field.
The pharmaceutical composition according to the invention can be carried out also in such dosage forms as a gel, ointment, cream, aerosol, or in any other dosage form suitable for topical application.
Below are several examples of the implementation of the pharmaceutical compositions according to the invention.
In relation to one hundred (100) male patients diagnosed with phimosis were conducted prospective studies. Patients were divided into two the group: 39 (thirty-nine) of the patients were aged from 1 year to 5 years (the average age of this group was 3.25 years) - it was a group of No. 1, and the remaining 61 patients were between the ages of 6 years to 30 years (mean age of this group was 12,49 year) - it was a group # 2. No patient had not previously been local or surgical treatment, none of the patients was not observed local inflammatory process. The treatment of all patients was topically applied pharmaceutical composition prepared in the form of ointments, with a content of 0.2% and betamethasone 150 UTR hyaluronidase. Patients were prescribed the application of the ointment once or twice a day to cure, but no longer than 12 weeks.
The application of the ointment was carried out by the patient or the parents of the child, the ointment was applied to the fibrous ring, after which the foreskin was subjected to careful pulling. Caution is necessary to avoid causing the patient pain or bleeding.
It was found that the treatment provided within the above mentioned period, is effective and leads to a complete cure of phimosis.
Patients were interviewed to determine the presence of symptoms of local irritation, urination disorders or bleeding during treatment.
To analyze and identify possible dependencies effectiveness of medication from the patient's age and duration of treatment necessary to achieve the improvement of the clinical status of the Oia, the results obtained for the above two groups, which were divided patients were compared. For statistical processing of results was applied T-student test (Student's T-Test for comparison of mean values was adopted 5%level of significance.
90% (ninety percent) of patients with clinical treatment, there is a marked recovery from phimosis, while in 32% of patients have been able to make significant pulling the foreskin without pain or bleeding, and in 58% of patients showed complete disappearance of the symptoms of phimosis.
Symptoms of local irritation, such as redness and feelings of local burning, occurred in 5% of patients, but these symptoms disappeared completely after a break in treatment. After a few days break, when the ointment was not applied, these patients resumed treatment, which gave satisfactory results. 5% (five percent) of the Patients required re-treatment, which gave satisfactory results.
The average time of use of the pharmaceutical compositions according to the invention was 38 days for patients aged 1 year to 5 years (group 1) and 42 days for a group of patients at the age from 6 years to 30 years (group # 2).
The statistical analysis did not reveal significant differences between the Timi two groups of patients in relation to clinical response or duration of application of the pharmaceutical composition, statistical results for the two age groups were similar (p>0,05).
Was prepared in a pharmaceutical composition for topical application in the form of a cream, which contained the following components:
Betamethasone - 0.2% of the total weight of the pharmaceutical composition;
Hyaluronidase - 150 UTR;
Ointment - 1,
The procedure of application of the pharmaceutical composition was similar to that which was described in the previous example, treatment was subjected to the following three patients diagnosed with phimosis.
Patient No. 1
The patient is 18 months old, diagnosed with phimosis, before it was subjected to treatment with a 0.05%hydrocortisone ointment, but to no avail. Treatment was begun with a local application of the above cream twice a day for four weeks, which resulted in the complete disappearance of the symptoms of phimosis.
Patient No. 2
The patient's age is 16 years old, young man, the age of sexual maturity, presence of phimosis. The same treatment was carried out for 8 weeks with all the signs of recovery appeared in the sixth week of treatment. It is testimony to the applicability of the pharmaceutical composition and for patients older ages.
Patient No. 3
The patient's age 7 years, the recurrence of phimosis after treatment by massage, contribute to the total exposure of the glans penis according to the instructions of the doctor-pediatrician. It was decided that for the treatment of secondary phimosis take up to 12 weeks. The effect of cure was achieved after 10 weeks of applying the cream.
|Patient No.||Age||Active ingredients cream||Duration||Cure|
|1||18 months||Betamethasone 0.2% hyaluronidase 150 UTR||Twice a day for 4 weeks||Full|
|2||16 years||Betamethasone 0.2% hyaluronidase 150 UTR||Twice a day for 8 weeks||Proper|
|3||7 years||Betamethasone 0.2% hyaluronidase 150 UTR||Secondary phimosis, twice a day for 10 weeks||Effective|
Examples of various clinical situations in which achieved good clinical results due to the application of the aforementioned cream, it was ensured prevention of surgical injury, and managed to avoid additional charges.
The pharmaceutical composition according to the invention was prepared using the following components:
|Bullish hyaluronidase||150 UTR;|
|Valerate betamethasone||2.5 mg;|
|Mineral oil||42.9 mg;|
|Solid vaseline q.s.p.||1 year|
Note: PEG 400 polyethylene glycol with a molecular weight of 400.
Examples 4, 5 and 6
The table below shows three examples of the implementation of the pharmaceutical compositions according to the invention.
|Components||Example 4||I Example 5||Example 6|
|Hyaluronidase||300 UTR||I 200 UTR||100 UTR|
|Valerate betamethasone||2,5mg||2,5mg||2.5 mg|
|Carbowax 4000||16,5 mg||82,5 mg||0|
|Nipigon||1 mg||1 mg||1 mg|
|Mineral oil||46,5 mg||0||are 162.5 mg|
|Alcohol 96°||0,007 ml||0,007 ml||0,007 ml|
|Carbowax 400||0||0||62.5 mg|
|Deionized water||0||0,0016 ml||0|
|Solid vaseline||q.s.p. 1 g||0||q.s.p. 1 g|
|Carbowax 400||0||q.s.p. 1 g||0|
1. The use of a pharmaceutical composition comprising a corticosteroid, for the preparation of medicaments for the treatment of phimosis with topical application, characterized in that the composition contains one or more corticosteroids and/or hormonal steroids in the range from about 0.025 to 5% by weight of the total pharmaceutical composition in combination with non-hormonal anti-inflammatory agents or without them and hyaluronidase in the amount of approximately from 25 to 4000 UTR per 1 g of the pharmaceutical composition in an environment suitable media, in different dosage forms with additives, well known to the average expert in the field.
2. The use according to claim 1,which is characterized in that the pharmaceutical composition, the corticosteroid is in the range of about from 0.05 to 3% of the total mass of pharmacy is practical composition, consisting of one or more corticosteroids.
3. The use according to claim 1, characterized in that used in the pharmaceutical compositions of the corticosteroid is selected from the following list: betamethasone, hydrocortisone, cortisone acetate, balarat, butyrate or valerate hydrocortisone, clobetasol or clobetasol propionate, propionate, dipropionate, valerate, phosphate, acetate or other esters of betamethasone dipropionate alklometazon, desoximetasone, pialat of clocortolone, diacetate diflorasone, acetonide or flurandrenolide fluoqinolona, acetate, methylprednisolone, mometasone furoate, diacetate, amcinonide or fluocinonide of diflorasone, propionate or desonide of halobetasol, triamcinolone acetonide and mixtures of these substances.
4. The use according to claim 1, characterized in that the content in the pharmaceutical composition hyaluronidase is in the range of about 75 to 2000 UTR per 1 g of pharmaceutical composition.
5. The use according to claim 1, characterized in that the corticosteroid, used as part of a pharmaceutical composition selected from the corticosteroid family of betamethasone and its derivatives.
6. The use according to claim 5, characterized in that the corticosteroid used in the composition of the pharmaceutical composition is 2-phenyl-1,2-Benzino-selenate-3(2H)-it is mainly in the form of a complex EPE is s such acids, as Valerian (betamethasone valerate), propionic (propionate betamethasone), dipropionate (betamethasone dipropionate), phosphorus (phosphate betamethasone) or acetic acid (acetate betamethasone).
7. The use according to claim 1, characterized in that the pharmaceutical composition used anti-inflammatory agents, preferably selected from the following list: diclofenac, ibuprofen, naproxen, fenoprofen, tolmetin, sulindac, meclofenamate, Ketoprofen, piroxicam, flurbiprofen, oxaprozin, while preferably using diclofenac.
8. The use according to claim 1, characterized in that in the form of pharmaceutical compositions as an anti-inflammatory agent used diclofenac.
9. The use according to claim 1, characterized in that the pharmaceutical composition in combination with a corticosteroid used hormonal steroids, such as testosterone.
10. The use according to claim 1, characterized in that the pharmaceutical composition is made in such dosage forms as a gel, ointment, cream, aerosol, or in any other dosage form suitable for topical application.
11. Ointment for the treatment of phimosis, which used corticosteroids topical application, characterized in that it contains betamethasone within about is 0.025 to 5% relative to the total weight of the pharmaceutical composition as corticosteroid with proteolytic diffusible enzyme hyaluronidase in the amount of approximately from 25 to 4000 UTR per 1 g of the pharmaceutical composition in an environment suitable media with additives, well known to the average expert in the field.
FIELD: organic chemistry, medicine, biochemistry.
SUBSTANCE: invention relates to new compounds of the formula (I) wherein R1 and R2 can be similar or different and represent independently (C1-C6)-alkyl that are selective inhibitors of enzyme phosphodiesterase, and to their pharmaceutically acceptable salts or stereoisomers. Also, invention involves a method for preparing the preferable compound, i. e. 5-[[2-ethoxy-5-(cis-2,6-dimethylpiperazin-4-ylsulfonyl)phenyl]]-1-methyl-3-n-propyl-7,6-dihydro-1H-pyrazolo[4,3-d]pyrimidine-7-one. Also, invention proposes new intermediate compounds used in method for synthesis of this compound. Compounds of the formula (I) show very high effectiveness in treatment of diseases associated with impotence, such as the male erectile sterility but they exhibit such features as prolonged therapeutic effectiveness and lower toxicity. Also, invention relates to a pharmaceutical composition used in treatment of impotence and using compound of the formula (I) in preparing the medicinal preparation designated for treatment of diseases associated with impotence.
EFFECT: valuable medicinal properties of compound.
8 cl, 7 ex
FIELD: medicine, gynecology, phytotherapy, pharmaceutical industry.
SUBSTANCE: invention relates to composition used in treatment of gynecological diseases in women. The composition for treatment of gynecological diseases in women comprises a mixture of the following dry medicinal plants: pot-marigold flowers, clinging bedstraw herb, swampy marsh cinquefoil herb, walnut walls, licorice roots and fenestrate Saint-John's-wort herb taken in the definite ratio of components. Also, the composition for treatment of gynecological diseases in women comprises a mixture of 30-40% alcoholic tinctures of medicinal plants: pot-marigold flowers, clinging bedstraw herb, swampy marsh cinquefoil herb, walnut walls, licorice roots and fenestrate Saint-John's-wort herb taken in the definite ratio. Proposed compositions promote to effective treatment of gynecological diseases in women.
EFFECT: valuable medicinal properties of compositions.
4 cl, 6 ex
FIELD: medicine, gynecology.
SUBSTANCE: invention relates to treatment of chronic inflammatory diseases of uterus cervix and vagina. Method involves administration of tampons with Baldonskaya mud by every other day by their alternating with intravaginal applications of the mixture consisting of 8-9 ml of avocado oil, 2-3 drops of tea tree oil with manuca and 1-2 drops of eucalyptus oil by 12 procedures for a course. Simultaneously the method involves oral administration of 1-2 drops of essential oil with honey that is drunk with green or mint tea and by alternating the using thyme, lemon and tea tree oils with manuca wherein each component is taken for 21 day with 14 days breaks between these administrations. Then after 3 months break 1-2 drops of lavender oil is given by the same schedule. On the background of above said therapy method involves application once per a week on the patient body the oil mixture consisting of 100 ml of basic oil, 7-8 drops of lavender oil, 6-7 drops of lemon oil, 9-10 drops of thyme oil and 13-15 drops of rosemary oil in combination in 2 h the bath comprising 2 table spoons of salt "San Aktiv", 5-6 drops of thyme oil, 3-4 drops of rosemary oil, 1-2 drops of lemon at temperature 37°C for 20 min. Such carrying out the method provides the effective therapy in women with allergy to antibiotics.
EFFECT: improved treatment method.
FIELD: medicine, gynecology.
SUBSTANCE: one should carry out intrauterine photohemotherapy with the help of special equipment for 45-50 min, 5 seances. Moreover, for interrupting acute manifestations of vaginal candidosis it is necessary to conduct therapy with antimycotic preparations once daily for 3 d, and since the 3d-4th d one should perform intrauterine photohemotherapy every other day at the mode "II", after photohemotherapy it is useful to continue antimycotic vaginal therapy for 3 d more. For treating chronic, relapsing forms of vaginal candidosis therapy with antimycotic preparations should be fulfilled locally every other day by alternating it with intrauterine photohemotherapy at modes "II" and "III". In 1.5-2 mo after the course of therapy it is suggested to carry out repeated course of intrauterine photohemotherapy at the mode "III", every other day, 5 seances.
EFFECT: higher efficiency of therapy.
1 cl, 1 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new compounds including all its enantiomeric and diastereomeric forms, and to their pharmaceutically acceptable salts wherein indicated compound corresponds to the formula: wherein A represents a conformationally limited ring system chosen from the group comprising the following formulae: (a) (d) and (e) wherein carbon atoms labeled by asterisks can be in any stereochemical configuration or their mixtures wherein Y has a formula: -(CH2)b-R15 wherein index b = 1-4, and R15 represents -OH, -NH2, guanidine-group, and Z has a formula: wherein R represents hydrogen atom; R9 represents naphthylmethyl; R10 represents -C(X)N(R16)2 wherein each R16 represents independently hydrogen atom or (C1-C10)-alkyl; X represents oxygen atom; or Z represents naphthylmethyl wherein W has a formula: wherein R represents phenyl substituted optionally with halogen atom of OH-group wherein fragment L is chosen from the group comprising: -NH- or -NHC(O)-; B represents hydrogen atom of fragment of the formula: wherein fragments R2, R3 and R4 are chosen independently among the group comprising hydrogen atom, -NHC(O)CH3, benzyl substituted optionally with hydroxy-group or halogen atom, imidazolylmethyl; or fragments R2, R3 and R represent in common naphthalinyl or isoquinolinyl; or one radical among R2, R3 and R4 represents hydrogen atom and two radical among R, R3 or R4 chosen in common form piperidine ring or tetrahydroisoquinoline ring substituted optionally with the group -C(O)CH3. Also, invention relates to a pharmaceutical composition possessing the agonistic activity with respect to MC-3/MC-4 receptors based on these compounds. Invention provides preparing new compounds and pharmaceutical compositions based on thereof for aims in treatment of disorders mediated by function of MC-3/MC-4 receptors.
EFFECT: valuable medicinal properties of compounds and compositions.
17 cl, 14 tbl, 12 ex
FIELD: veterinary medicine.
SUBSTANCE: method involves intramuscularly introducing dimethyl pyrazolyl selenide at a dose of 10 mg/kg 20-30 days before planned delivery term.
EFFECT: reduced risk of puerperal complications and toxic effect.
FIELD: medicine, gynecology, immunology.
SUBSTANCE: for microenemas carried out just before galvanization according to abdominal-sacral technique one should apply 1%-chitosan ascorbate gel at the quantity of 20 ml, at temperature of 36-38° C, once daily, about 8-9 procedures/course. The present innovation enables to decrease inflammatory conglomerate and prevent massive adhesion-formation due to creating rectal enterosorbent depot that enables to enhance the sorption of toxic products through rectal wall out of inflammation focus.
EFFECT: higher efficiency of therapy.
1 ex, 3 tbl
FIELD: medicine, gynecology.
SUBSTANCE: as a suggested preparation one should apply dried defibrinated or non-defibrinated blood of Siberian stags or spotted deer. The preparation suggested should be prescribed perorally per 25 mg (1 capsule) twice daily, therapy course corresponds to 25-35 d. Application of this preparation in women at normal level of gonadotropins, positive gestagen-test, with no hyperandrogenia and hyperprolactinemia at the absence of menstrual cycle of more than 3 mo provides the onset of menstruations at stable positive effect. After carrying out 3 therapeutic courses no relapses had been observed.
EFFECT: higher efficiency for regulating menstrual cycle.
3 cl, 2 ex, 3 tbl
FIELD: medicine, gynecology.
SUBSTANCE: one should carry out galvanization during 15 min due to applying electrodes along abdominal-sacral technique. Just before galvanization one should introduce 15 ml 2%-chitosan ascorbate gel containing metronidasol at the dosage of 2 mg/ml gel, intravaginally at 36-38° C. Procedures should be carried out once daily, therapy course lasts for about 7-8 d. The innovation suggested provides total curative effect of antibacterial remedies and galvanization at decreased dosage of metronidasol and, thus, enables to obtain stable remission of salpingo-oophoritis.
EFFECT: higher efficiency of therapy.
1 ex, 1 tbl
FIELD: veterinary science.
SUBSTANCE: the suggested preparation contains enrofloxacin, dimethyl sulfoxide, furacriline and distilled water at the following ratio of components, weight%: enrofloxacin 0.3-0.5, furacriline 0.021-0.027, dimethyl sulfoxide 38-50%, distilled water - the rest. The preparation should be introduced due to intrauterine injections, in sows - with the help of special equipment for artificial insemination. Against other analogs the preparation is of wider range of anti-microbial action and high anti-microbial activity.
EFFECT: higher efficiency of therapy and prophylaxis.
6 ex, 6 tbl
FIELD: pharmaceutical industry.
SUBSTANCE: invention relates to creating drugs for treatment and prevention of inflammatory lesions of support-motor apparatus (myosites, arthrites, tendovaginites, etc.). Therapeutical composition according to invention contains, wt %: essential oil of silver fir 1.0-2.0, camphor 4.0-5.0, oil extract of red capsicum 0.06-0.08, biologically active component isolated from medicinal leech or its parts 0.01-6.5, Ibuprofen 60.0-65.0, ethoxydiglycol 3.0-5.0, Emulgin B2 0.4-0.6, Carbomer 0.5-0.8, triethanolamine 0.6-0.8, methylparben 0.2-0.3, propylparben 0.02-0.03, butyloxyanisol 0.08-0.1, Bronopol 0.04-0.05, and water the rest. Composition activates metabolic processes in skin and subcutaneous fat layer, normalizes blood supply, eliminates stagnant phenomena, accelerates getting active therapeutical substances into membranes of biological cells, which results in rapid achievement of stable therapeutical effect in what concerns elimination of inflammatory process in joints and muscles.
EFFECT: increased therapeutical efficiency.
FIELD: pharmaceutical industry and cosmetics.
SUBSTANCE: composition contains, wt %: biologically active component isolated from medicinal leech or its parts 0.01-6.0, menthol 0.15-0.25, aqueous-alcoholic extract of horse-chestnut fruitage 8-10, camphor 0.15-0.30, ethoxydiglycol 3-5, polyethyleneglycol 1500, 0.8-1.2, emulgin B2, 0.8-1,2, Carbomer 0.6-0.8, triethanolamine 0.6-0.8, methylparben 0.25-0.35, Bronopol 0.04-0.06, butyloxyanisol 0.06-0.08, and water to 100%. Composition is made in the form of gel and provides antithrombic and analeptic effects on skin and hypodermic tissues, enhances antiinflammatory action, favors deep penetration of active components through skin, strengthens venous vessel walls, improves microcirculation of blood, and accelerated restoration of vascular wall tone.
EFFECT: expanded therapeutical possibilities.
2 cl, 2 tbl
FIELD: pharmaceutical chemistry.
SUBSTANCE: agent contains active components foridonum (3.00-6.00%) and isosorbide dinitrate (3.00-6.00%) with pharmaceutically acceptable gel base. The latter is composed of thickener, non-aqueous hydrophilic solvents, hydrophobic solvents, preservative, neutralization agent, emulsifier, and purified water.
EFFECT: increased bioavailability of active components and reduced or suppressed negative side effects such as locally irritating effects.
9 cl, 3 tbl, 14 ex
FIELD: medicine, pharmaceutical industry, pharmacy.
SUBSTANCE: invention relates to an anti-inflammatory ointment with hypolipidemic effect. Proposed ointment comprises ephthylline-base for ointment, a statin wherein lescol (fluvastatin) is used as statin, and ephthylline comprises 40% of ephthiderm. Invention provides enhancing the curative effect and hypolipidemic effect and effects on enzymatic systems of biological membranes that results to prolongation of curative effect of ointment.
EFFECT: valuable medicinal properties of ointment.
3 cl, 2 tbl
FIELD: cosmetology, esthetic surgery, applied biopharmacology.
SUBSTANCE: invention relates to medicative and cosmetic agents, and uses of biologically active substances based on natural biological complexes. Claimed method includes application of Mirralgin balm having analgesic, anti-inflammation and resolving action, Reventon balm, having vessel restorative action, for edema reducing and microcirculation improving. In process of blepharoplastic eye boundary bandage microemulsion having recovery and animative action on eaves skin is applied, and in process of facelifting cream mask having bactericide, vessel restorative and recovering action, and enhancing of local immunity is applied. Mirralgin balm and Reventon balm treatment is carried out sequentially or alternatively. In another embodiment after skin cleaning and treatment of damaged zone with anti-septic agent Bacteriophage gel, which disinfects skin surface, prevents biofilm forming, accelerates cicatrizing process is applied, then posttraumatic zone is treated with cleaning milk, toned up with tonic lotion and cream mask having bactericide, vessel restorative and recovering action, and enhancing of local immunity is applied.
EFFECT: method for skin structure recovering without skin trauma.
4 cl, 7 ex, 1 tbl
FIELD: veterinary science, medicine, pharmacy.
SUBSTANCE: invention relates to agents used in treatment of dermatomycosis in animals and humans. Ointment for treatment of dermatomycosis in animals and humans comprises acetylsalicylic acid, 5% iodine alcoholic solution and glycerol taken in the definite ratio of components. Invention enhances effectiveness of treatment, decreases time in treatment of dermatomycosis and prevents appearance of new foci of diseases and relapses.
EFFECT: enhanced effectiveness of treatment.
FIELD: medicine, contraception.
SUBSTANCE: invention proposes antibacterial and contraceptive compositions that comprise the following components: (1) matrix-forming substance; (2) bioadhesive substance; (3) buffer substance; (4) moistening substance, optionally; (5) preserving agent, optionally, and (6) water. Proposed compositions are suitable for their placement into vagina wherein compositions form semisolid matrix in contact with testicular fluid, cause thickening cervical mucus, form a bioadhesive layer on vagina surfaces, maintain the natural acid pH value in vagina about less 5 in the presence of testicular fluid ejected by a male and don't disturb essentially the natural microbiological balance in vagina. Compositions and methods decrease and/or prevent transfer of diseases transferring by sexual way and act as vaginal contraceptives with less adverse effect as compared with conventional vaginal contraceptives and can be used therefore for a long time. Compositions and methods are simple for using and don't require a physical device for their retention into vagina during using.
EFFECT: improved and valuable properties of compositions and methods.
36 cl, 17 tbl, 11 ex
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to an agent for topical using used in treatment of joint diseases. The proposed agent comprises glucosamine salt, chondroitin sulfate and dimethylsulfoxide incorporated into an acceptable ointment base. Invention provides enhancing effectiveness due to using low-molecular saccharides that results to elevating diffusion delivery rate of the substance to the joint zone and providing the achievement of synergistic effect in treatment of joint diseases.
EFFECT: enhanced effectiveness and valuable medicinal properties of agent.
2 cl, 3 ex
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to preparations for external using in treatment of joint diseases. The proposed agent comprises a saccharide - glucosamine salt and dimethylsulfoxide incorporated into an acceptable ointment base. Invention provides enhancing effectiveness of agent due to using low-molecular saccharides that results to the elevating diffusion delivery rate of active substance to the join zone.
EFFECT: improved and valuable properties of agent.
2 cl, 5 ex
FIELD: medicine, dermatology, pharmacy.
SUBSTANCE: invention relates to a pharmaceutical gel composition for applying on skin. The composition comprises at least one vitamin D or analog of vitamin D, at least one corticosteroid, at least one solvent and an excipient enhancing viscosity. Viscosity value of the composition is in the range from 5 mPa x s to 500 mPa x s. The composition is designated for treatment of psoriasis and associated states in humans. The composition is suitable for applying on skin, shows the improved absorption and stable at 40°C in storage for 3 months.
EFFECT: improved and valuable properties of composition.
22 cl, 2 tbl, 1 ex
FIELD: veterinary science.
SUBSTANCE: the present innovation deals with preventing and treating diseases caused by animal endoparasites. Anti-parasitic preparation contains closantel or its sodium salt dissolved in the main solvent as polyethylene glycol, propylene glycol, triethylene glycol or their mixtures, the suggested preparation contains, also, novocain (or lidocain, or anaesthesin), ethanol and/or isopropyl alcohol, polyvinyl pyrrolidone, benzyl alcohol and water at certain ratio of components. The innovation provides high efficiency of anti-parasitic action at no pain and inflammatory reaction in animals both at intramuscular and subcutaneous types of injection, moreover, decreased milk yields in cows haven't been observed.
EFFECT: higher efficiency.
1 cl, 96 ex