Low-concentrated peroxide for treatment or prevention of vaginal infections

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, particularly, to pharmaceutical vaginal compositions for treatment or prevention of vaginal infections. Composition contains synergistic mixture of bioadhesive medicinal form of prolonged release which reduces value pH and includes peroxide in amount, sufficient to increase oxygen concentration without either vagina sterilisation or considerable destruction of normal required local vaginal flora. Invention also refers to method of treatment or prevention of vaginal infections, including vaginal introduction of pharmaceutical vaginal compositions in amount, sufficient to decrease pH and increase in oxygen concentration without either vagina sterilisations or considerable destruction of normal desirable local vaginal flora.

EFFECT: development of effective method of treatment and prevention of vaginal infections.

35 cl, 1 tbl, 1 ex

 

Related applications

This application claimed priority of provisional application for U.S. patent No. 60/330683, filed October 29, 2001, the contents of which are incorporated here by reference.

The scope of the invention

This invention relates to a pharmaceutical composition for the treatment or prevention of vaginal infections. Typically, the pharmaceutical composition comprises a synergistic mixture bioadhesive dosage forms with prolonged release, which releases and maintains a very low peroxide concentration over a long period of time to ensure positive action release oxygen while reducing the pH in the course of time, but without excessive concentration of peroxide. The invention relates to a method of treatment of vaginal infections with the use of the pharmaceutical compositions disclosed here.

Background of invention

Vaginal infections are a common problem in women. Bacterial vaginosis (BV) is the most common form of infectious vaginitis, constituting 45% of cases with characteristic symptoms, and found that in 15% of cases the disease is asymptomatic active in sexual against women. See J. Breen ed., The Gynecologist and the Older Patient, pp. 304-305 (1988). Polaha is t, this polybacterial vaginal infection is caused due to the increase in the number of anaerobic microorganisms with a concomitant decrease in the number of lactic acid bacteria in the vagina. The decrease in the number of lactic acid bacteria in the vagina has a double effect, which leads to i) reduced competition for nutrients and ii) the reduction of the number present lactic acid, which allows you to multiply conditionally pathogenic microorganisms in the vagina, the growth of which in norm inhibited lactic acid bacteria. I believe that the main pathogens associated with BV are Gardnerella vaginalis and anaerobes Mobiluncus species. However, it is believed that the etiology of vaginitis attended numerous other pathogenic anaerobes. See Kaufman et al., Benign Diseases of the Vulva and Vagina, 3rded., pp. 401-418 (1989). Thus, BV is an infection caused by a wide range of pathogens, for treatment of which requires the treatment of a wide spectrum of action.

In the United States every year millions of women are forced to go to the doctor for help in the discharge and unpleasant odor caused by BV. It is established that even more, it is 30% of all adult Americans, applies a douche means that they buy without prescription. The idea of washing away the discharge with an unpleasant odor acid src is navaneet is a simplified approach. In the medical attitude towards douching are negative, as there are reports about the relationship between douching and PID (pelvic inflammatory disease organs), ectopic pregnancy, obstruction of pipes or reduced fertility. In addition, douching is undesirable due to the fact that at the time it is washed normal and healthy bacterial flora, which makes the environment susceptible to the recurrence of BV.

The most disturbing aspect of BV is its effect on the quality of the implantation of the fetus and the potential ability to cause premature birth. There are reports that the distribution of BV in pregnant women ranges from 13 to 31%. The presence of BV during pregnancy is associated with increased risk of miscarriage late in pregnancy, premature birth, and the occurrence of postpartum endometritis and low weight newborns. In a recent study it was shown that BV is associated with an increased risk of miscarriage in the first trimester in women who have undergone in vitro fertilization.

In the application for U.S. patent No. 09/748753 disclosed compositions for the prevention of miscarriage and preterm birth associated with bacterial vaginosis, by tebufelone pH of the vagina. The composition disclosed in the application, contains a therapeutically effective amount of a water pH sautereau biodesulphurization in water, but swellable in water Poperechnaya polymer polycarboxylic acid, which provides a therapeutic effect without the need for any additional therapeutic agent, in and of itself sabatieria pH of the vagina to its normal acidic pH values, is detrimental to the pathogen.

Clinically BV is superficial vaginal infection with multiple symptoms of irritation and without inflammatory response. Some symptoms include unpleasant odor, increased the pH value of the vagina, i.e. higher than about 5.0 and weak homogeneous discharge, the presence of cells Cardnerella clue and a high ratio of succinate/sodium lactate (not less than 0.4). See, for example, Livengood et al., "Bacterial Vaginosis: Diagnostic and Pathogenic findings during Topical Clindamycin Therapy", Am. J. Obstet. Gynecol., Vol. 163, No. 2, p. 515 (August, 1990).

Suppose that the composition of organic acids in the vagina is shifted mainly from lactic acid (pKand= 3,86) to succinic acid (pKA1=4,27, pKA2=5,64) by reducing the number of lactic acid bacteria that produce lactic acid, and increase the number of Mobiluncus that produce succinic acid. This shift in the composition of acids leads to the increase of pH of the vagina. It remains unclear whether the change in the acidity of the cause or effect of the infection. However, it is known that some n is desirable anaerobes grow better at higher pH value, than there is in the vagina is normal. Thus, it is believed that the reduction of vaginal pH to a normal level in healthy condition is effective against the symptoms of the infection, if not against the infection.

In addition, it is known that the smell of amines, which are formed in the vagina during BV, is enhanced at higher pH values due to the fact that diprotonirovannyye volatile amines prevail to a greater extent at higher pH, as the environment becomes more alkaline. In addition, I believe that higher pH promotes the growth of unwanted anaerobes and production of odor causing amines that are associated with bacterial vaginal infection.

In U.S. patent No. 6017521 ('521 patent") discloses a method of treating BV local contacts the cavity surface of epithelial cells of the vagina with effective sautereau pH of the aqueous composition comprising water and an effective amount of swelling in water, but insoluble in water Poperechnaya sautereau pH, bioadhesive polymer in which at least 80% of the monomers constituting the specified polymer contain at least one carboxyl group. The composition is brought into contact with the cells of the vagina for a period of time sufficient to reduce the pH of the vagina until the acid value of R is. In patent '521 argues that the composition does not contain any therapeutic agents.

The exact role of H2About2-producing lactic acid bacteria remains largely unclear. This may be the result of several factors, the most important of which is concentration. Detection of H2About2-producing lactic acid bacteria does not mean that they are present in sufficient concentration for oxygen saturation vagina and fostering an environment detrimental to anaerobes. Many researchers have proposed to introduce into the vagina N2About2-producing lactic acid bacteria in high concentrations as a means of treatment of the infection. The technical difficulties that arise when this approach did not allow the researchers to develop a really fruitful treatment.

Other efforts the introduction of H2About2in acidifying agent for the vagina. However, these attempts failed for two reasons. First, N2About2unstable in the gel, and it cannot be stored in a commercial environment. Secondly, the concentration of H2About2has a tendency to rapidly release immediately, causing explosive action, destroying not only anaerobes, but also resulting in sterilization of the vagina, making women more sensitive to what eridium vaginal infections.

Such treatment is disclosed in U.S. patent No. 5741525 ('525 patent"). In patent '525 reveal ways to maintain or improve the normal protective function of the microflora of the vagina by the introduction of a therapeutically effective amount of a composition containing hydrogen peroxide in an amount from about 0.1% to about 3.0 percent. In patent '525 argues that the peroxide in amounts below about 0.1% does not have any significant inhibitory effect on a wide range of microorganisms. (Patent '525 column 5, line 57-59). However, the concentration of hydrogen peroxide that is claimed in the patent '525, as suitable for the treatment of BV, often have a detrimental effect on the growth of beneficial microflora and can cause severe irritation of the vagina and even burns vagina peroxide. In addition, the treatment simply is a sudden, instantaneous release of peroxide, which leads to the death of a significant number of bacteria and leaves in question the chance for the development of beneficial bacterial flora or, on the contrary, contributes to the recurrence of BV.

Thus, there is a need for effective pharmaceutical composition for the treatment of vaginal infections such as BV, which would not "explosive action", causing irritation of the vagina and substantially inhibiting or destructive acting on the microflora. In addition there is a need in the pharmaceutical composition, with the help of which it would be possible to treat BV without sterilization and significant loss of normal, desirable local microflora of the vagina and maintain the sensitivity to the recurrence of BV. Also there is a need for pharmaceutical compositions that can simply be applied which effectively balance between the inhibition of undesirable microorganisms, while ensuring a favorable environment for the desired local microflora. The present invention successfully focused on data needs, as described in detail below.

Brief description of the invention

The invention relates to pharmaceutical compositions for the treatment or prevention of vaginal infections. The pharmaceutical composition comprises a synergistic mixture of a peroxide source and bioadhesive polymeric dosage form with prolonged release. In one embodiment of the invention a synergistic blend designed to release peroxide over a period of time, which is usually at least 12 hours and often more than 48 hours. In an additional embodiment of the invention a synergistic mixture releases peroxide in the amount of less than 0.1% by weight per hour. In an additional embodiment of the invention a synergistic mixture contains less than 0.1% by weight of peroxide. Peroxide released in each of these embodiments, is sufficient for therapeutic increasing oxygen concentration, while the polymer with a long release reduces the pH value, thereby significantly inhibiting the growth of anaerobic bacteria that cause BV, without sterilization of the vagina or a significant loss of normal desirable local microflora of the vagina. As soon as anaerobic microorganisms cease to prevail in the environment, BV will succumb to prevention or treatment.

Bioadhesive polymeric dosage form with prolonged release of ignitable bioadhesive swelling in water, insoluble in water poperechnyy polycarboxylic polymer. A non-limiting example of such polymer is polycarbophil.

In one preferred embodiment of the synergistic mixture contains carbamide peroxide as the source of peroxide in a mixture with polycarbophil as a polymer.

The invention additionally relates to a method of treating or preventing vaginal infections. The composition is introduced into the vagina of the woman in need of such treatment, providing a therapeutically effective amount of vaginal pharmaceutical compositions disclosed herein without material adverse effect on the normal, desirable local flora.

Such description is their preferred embodiments of the invention

The present invention is based on the use of unexpectedly low concentrations of peroxide for a long period of time to ensure positive action treatment or prevention of vaginal infections without sterilization vaginal peroxide or a significant loss of normal desirable local microflora of the vagina or significant irritation to the sensitive tissues of the vagina.

The expression "normal desirable local microflora of the vagina" means the bacteria that normally reside in the vagina of healthy women. Normal microflora, for example, includes the family of lactic acid bacteria in humans, such as Tissier''s bacillus. The microorganisms that make up the normal flora, are well known (for example, see Principles and Practice of Infectious Diseases, 3rded., 1990, G. Mandell et al., ed., Churchill Livingstone Inc. New York).

The expression "significant loss"as it is used here, means a substantial sterilization of the vagina in relation to the beneficial bacteria found in the normal environment of the vagina when not in sufficient quantity normal desirable local microflora of the vagina and want to colonize the vagina microorganisms after treatment.

In addition, the term "vaginal infection" includes any type of microorganism infecting the vagina of the patient, the which does not apply to normal desirable local microflora of the vagina such as bacterial or fungal infection, and particularly includes BV.

The term "peroxide source," as it is used here, is a compound, which may be released peroxide. To illustrate the value of a peroxide source in contrast to most peroxide you can give the following example. If vaginal pharmaceutical composition is used by 0.1%-0,25% by weight carbamide peroxide (peroxide source), the amount of peroxide, taking into account the part that belongs to the urea will be approximately from 0,034 to 0,085% by mass.

The term "dose" or "dosage form"as used in the description and the claims, means physically separate amount of the pharmaceutical composition, suitable for use as doses in women. Each dose contains a predetermined quantity of a peroxide source, calculated to produce the desired therapeutic effect, in combination with the required pharmaceutical carrier. Of course, the amount of peroxide in the dose may change to ensure the release of peroxide in different concentrations or different amounts for different periods of time.

One embodiment of the present invention is vaginal pharmaceutical composition suitable for the treatment of vaginal infections, especially BV. Typically, the components of ice includes a synergistic blend of bioadhesive dosage forms with prolonged release, which contains peroxide. Peroxide is released in a quantity sufficient for therapeutic increasing oxygen concentration, while the polymer with a long release also reduces the pH value, providing effective treatment or prevention of BV without sterilization of the vagina and a significant loss of normal desirable local microflora of the vagina.

In a particular embodiment of a vaginal composition for the release of peroxide for at least 12 hours, preferably for at least 24 hours and even more preferably for at least 48 hours. Other dosage forms of the composition is designed to release peroxide over a period of time at least equal to 72 hours and at least 96 hours. The greater the period of time covered by a single dose, the less will be required the introduction, in the case where it is desirable introduction of successive doses.

Additional non-limiting embodiment of a vaginal composition comprises a synergistic mixture that releases peroxide in the amount of less than 0.1% hydrogen peroxide per hour. Preferably, the peroxide would be released in quantities less than 0,085% peroxide per hour. The compositions disclosed here, which releases low amounts of peroxide are surprisingly effective the La treatment and prevention of vaginal infections without adversely affecting typical of higher concentrations.

Some women have natural flora producing peroxide lactic acid bacteria disappears. These women dosage forms disclosed here, are used to override the function of these microorganisms and provide a more favorable environment for other normal desirable local microflora of the vagina.

In an alternative embodiment of the invention vaginal pharmaceutical composition contains less than 0.1% hydrogen peroxide in a composition intended for administration to the patient. In this embodiment, the amount of peroxide to release over time is very low, but at the same time sufficient for the treatment or prevention of vaginal infections.

The peroxide source may be selected from a variety of sources, both organic and inorganic. Typical sources of peroxide are those used for the treatment of mucosal and related epithelial tissues, and especially those which are used in dentistry for teeth whitening. Preferably, the peroxide source is one of the following forms: hydrogen peroxide, including its complexes (e.g., carbamide peroxide); alkylperoxide (for example, di-tert-butylperoxide); benzoylperoxide (for example, benzo peroxide is silt); peroxyacids (e.g., m-chloroperbenzoic acid, paroxetina acid and its salts, peroxomonosulfate acid and its salts esters of peroxyketal (for example, tert-butylperbenzoate); dialkylamide (for example, di-tert-butylnitrone).

Preferred sources of hydrogen peroxide include carbamide peroxide, alkylperoxide, benzoylperoxide or dialkylamide. However, most preferably, the peroxide source was carbamide peroxide.

Preferred bioadhesive polymer system according to the invention has the advantage to keep the vagina and ensure long lasting release of peroxide for a long period of time, i.e. from 48 to 72 hours or more, and provide tebufelone pH within normal physiological limits. In contrast, most of the systems for delivery of drugs washed down with vaginal walls less than 4 hours. The polymer holds the peroxide source and slowly releases it over time. Preferred bioadhesive media includes bioadhesive swelling in water, insoluble in water poperechnyy polycarboxylic polymer. Especially preferred bioadhesive composition, which may be in the form of a gel, contains the basis of polycarbophil designed for controlled long is svobodne peroxide over time.

Typically, the composition releases peroxide for at least 12 hours and preferably for at least 24 hours. However, more preferably the peroxide is released for at least 48 hours and sometimes even more than 72 hours. Similar dosage forms with prolonged release, though with other therapies described in U.S. patent No. 5543150 and 6126959, the contents of each of which is specifically incorporated here by reference.

The specific dosage form to deliver peroxide preferably includes a composition based bioadhesives insoluble in water, swelling in water, Poperechnaya polycarboxylic polymer. An example of such dosage forms is basically described in U.S. patent No. 4615697 ('697 patent"), the contents of which is specifically incorporated here by reference. As a rule, at least 80% of the monomers of the polymer in the composition will contain at least one carboxyl functional group. Cross crosslinking agent should be present in such numbers, to adequately provide bioadhesion to maintain the system, attached to Milenium epithelial surfaces for a sufficient period of time to have taken place the desired dosage.

With the introduction of the vagina Le is artena form preferably remains attached to the epithelial surfaces during the period of time from about 24 to 48 hours or more. Similar results can be assessed clinically for various periods of time testing of samples from the vagina to reduce the pH due to the prolonged presence of the polymer. This degree of bioadhesive usually achieved when poperechnikami agent is in an amount of about from 0.1 to 6 wt.% to the polymer, preferably about 1 to 2 wt.%. Bioadhesion can also be defined using industrially available surface tensiometer used to determine the strength of adhesion.

Polymer dosage form can be adapted for regulating the speed of release of peroxide, changing the amount of Poperechnaya agent in the polymer. Suitable cross linking agents include Divinington, divinylbenzene, N,N-diallylamine, 3,4-dihydroxy-1,5-hexadiene, 2,5-dimethyl-1,5-hexadiene and similar agents.

The preferred polymer for use in such a dosage form is polycarbophil, USP, which is industrially available from a Noveon, Inc., of Cleveland, Ohio under the trade name of a Noveon®-AA1. Polycarbophil is polyacrylic acid cross-linked diphenylglycine.

Other suitable bioadhesive polymers that can be used in such a system for delivery of a drug referred to in the patent the '697. Nab is emer, these include polymers are polyacrylic acid, cross stitched 3,4-dihydroxy-1,5-hexadiene, and polymers of poly (methacrylic acid cross-linked divinylbenzene.

Typically, these polymers are not used in the form of their salts, as this will lead to a significant reduction in their ability to bioadhesive. Salts of divalent metals such as calcium salts, lead to the greatest reduction of bioadhesive. Salts of monovalent metals such as sodium, have no tendency to decrease bioadhesive to the same extent.

Such bioadhesive polymers can be obtained by conventional free radical polymerization using initiators such as benzoyl peroxide, azobisisobutyronitrile and the like. Examples of obtaining the appropriate bioadhesive polymers are given in the patent the '697.

Bioadhesive dosage form may be in the form of a gel, cream, pill, pills, capsules, suppository, film, or any other pharmaceutically acceptable form, which is attached to the mucous membrane and is not easily washed away. The preferred dosage form of the present invention is in the form of a gel.

Additives such as those described in the patent the '697, can be mixed with Poperechnaya polymer in the dosage form for maximum desired efficiency of the delivery system or for whom the ORT in the patient. Such additives, as an example, and without limitation, include sliding agents, plasticizers, preservatives, geleobrazovanie, the originators of tablets, the originators of pills, the originators of suppositories, binders, kremoobraznoyi, baking powder, casings, binders, carriers, colorants, agents that enhance the taste and/or smell, humidifiers, agents regulating the viscosity, the agents for bringing the pH and similar agents.

Mainly peroxide can be delivered and the pH value can be reduced for a long period of time using bioadhesives of polycarbophil. Polycarbophil represents the polymer in a low degree of cross stitched diphenylglycine. Also polycarbophil is a weak policistoj containing many carboxyl groups, which are a source of negative charges. Data acidic groups form hydrogen bonds with the cell surface. Hydrogen bonds are weak, but in the case of polycarbophil they are numerous and, therefore, contribute to the adhesion. Polycarbophil is water-insoluble polymer, and he remains attached to the epithelial cells of the vagina, until they are updated, usually within 3-5 days. Because polycarbophil is weak policycato with a very high buffer pursue the activities it supports the value of vaginal pH in the physiological range when 5 and, thus, contributes to the protection against infection. It was shown that the effect persisted for more than 96 hours. Polycarbophil has a pKa value equal to 4.3, and, like all good buffers, it supports an environment that is close to its pKa.

The polymer described in the patent the '697, can be adapted to control the speed of release of peroxide, for example, changing the amount of cross linking agent. Usually the rate of release of the peroxide source from the dosage form is always approximately zero on the number located a source of peroxide, after a slight initial "burst" release. Therefore, the person skilled in the art will easily make up the composition so that the duration and rate of release will be reported to deliver adequate amounts of peroxide. A typical composition of the polymer remains in place, usually within about 48 hours.

A non-limiting example of a suitable composition for delivery of peroxide in the vagina includes polycarbophil, carbomer, Natrosol®250 NNC, glycerin, sorbic acid, methylhydroxybenzoate and purified water, mixed with a peroxide source, preferably carbamide peroxide or benzoyl peroxide.

erbenova acid, methylhydroxybenzoate are preservatives, which can be replaced with other known preservatives such as benzoic acid, propylparaben, or propionic acid.

Carbomer is gelling, preferably Carbopol 974P, but instead you can use other geleobrazovanie, including, but not limited to, Carbopol R, Carbopol 980, methylcellulose or propylethylene.

Natrosol®250 NNC is an agent that increases the viscosity, instead of which it is possible to use other known agents that increase viscosity, such as methylcellulose or propylethylene. Natrosol®250 NNC is industrially available from Hercules, Inc., located in Wilmington, Delaware.

Glycerin is a humectant; alternatively moisturizers include, for example, propylene glycol and dipropyleneglycol.

Specialists in this field, obviously, it is clear that the composition can be altered to influence certain properties. For example, the concentration bioadhesive polymer can be increased to provide more or less bioadhesive. The viscosity can be changed by changing the pH or by changing the concentration of polymer or gel. The pH value can appropriately be changed to influence the rate of release or bioadhesive properties of the composition. All the ingredients are well-known and industrially available is t known providers.

In the preferred embodiment of the invention includes a vaginal composition containing polycarbophil and carbamide peroxide in a synergistic mixture designed to release peroxide for at least 24 hours.

The preferred percentage of peroxide source to be included in the pharmaceutical composition generally is in the range from 0.01% to 15%, more preferably from 0.1% to 10% and most preferably from 0.25% to 7%.

Typically, the source of peroxide is dosed amount of vaginal pharmaceutical composition where the metered quantity is in the range from 0.5 g to 2.5 g, and the source of peroxide is in an amount of about 0.01 mg to 500 mg However, preferably, if the peroxide source is in the composition in amount in the range of from about 0.1 mg to 75 mg, and more preferably in an amount of from 1 mg to 50 mg

Typically, the amount of peroxide in the dosage form is in the range from 0,0035 mg to 350 mg, However, preferred if the compositions contain from 0.01 to 100 mg and more preferably from 0.1 mg to 75 mg peroxide.

The present invention also relates to a method of treatment or prevention of vaginal infections in women. The method comprises the introduction into the vagina synergistic mixture bioadhesive dosage forms with prolonged release, the which releases and maintains a low concentration of peroxide.

The method can be used to maintain the normal activity of the microflora of the vagina. For example, if the patient is pregnant, and especially if it has a risk of miscarriage, a metered amount of the pharmaceutical compositions described here, you can enter the patient for the treatment or prevention of BV. As discussed above, BV during pregnancy has a negative impact on the quality of the implantation of the fetus and potentially can cause premature birth. The present invention is suitable for the prevention or treatment of BV in pregnant women or women seeking to get pregnant, and therefore reduce the risk of miscarriage and low weight newborns.

The compositions described here, you can enter the patient putting them into the vaginal cavity using conventional tools for administering drugs into the cavity, known in this field, such as (without limitation) the syringe, the syringe or manually. One of the delivery methods is the use of devices similar to those described in U.S. patent No. D345211 and D375352. These devices are elongated probe with one end open and with the other end, containing a large part of the composition for introduction into an airtight container, which the patient may be relatively easy to use. Containers also retain the composition is a therapeutic tool in a sealed, sterile environment prior to use. When using the container is opened and the open end into the vagina, while the other end is squeezed to deliver the contents of the container into the vagina. Can also be used such devices for delivery as a tampon for injection or other coating and impregnating means. "Set" product, therefore, may contain a single dose or multiple doses of the product.

The number of vaginal pharmaceutical compositions in dosage generally is at least 0.5 g and not more than 3, a Typical and preferred in this case, the dose of gel medium is in the range from 0.75 g to 2 g, and most preferably from about 1 g to 1.5 g per dose.

Mainly, the dosage can be such that it can be applied two or more times per day or once or less than once a week. Preferably, the dose amount thus to apply it once a day and most preferably once in two weeks or even a week.

Examples

In the following examples represent preferred compositions according to the invention. All percentages are based on percent by weight of the prepared composition, unless otherwise specified, and in General make up 100% by weight. Sources used peroxide for illustrative the goals in these examples was a carbamide peroxide or benzoyl peroxide, but, as explained above, it is possible to use other sources of peroxide.

Alternative dosage forms based on carbamide peroxide
Carbamide peroxide0,10%0,10%0,25%1,00%0,25%
Polycarbophil, USP2,00%2,00%2,00%2,00%1,00%
Carbopol 974P1,00%1,00%1,00%1,00%-
Natrosol® 250 HHX----2,00%
Glycerin, USP/BP12,90%15,00%12,90%12,90%12,90%
Sorbic acid NF/European Pharmacopoeia0,08%0,80%0,08%0,08%0,08%
Methylhydroxybenzoate NF, European Pharmacopoeia0,18%0,18%0,18%0,18%0,18%
Purified water, USP, European Pharmacopoeia83,74%80,92%83,59%82,84%83,59%
In General100%100%100%100%100%
Alternative dosage forms based on carbamide peroxide
Carbamide peroxide0,25%to 5.00%to 5.00%10,00%14,00%
Polycarbophil, USP1,00%2,00%1,00%2,00%2,00%
Carbopol 974P-1,00%-1,00%1,00%
Natrosol® 250 HHX2,00%-2,00%--
Glycerin, USP/BP14,00%12,90%12,90%12,90%12,90%
Sorbic acid NF/European Pharmacopoeia0,08%0,08%0,08%0,08%0,08%
Methylhydroxybenzoate NF, European Pharmacopoeia0,18%0,18%0,18%0,18%0,18%
Purified water, USP, European Pharmacopoeia82,49%78,84%78,84%73,84%69,84%
In General 100%100%100%100%100%
Alternative dosage forms based on benzoyl peroxide
Benzoyl peroxide0,20%0,20%0,50%0,50%0,50%
Polycarbophil, USP2,00%2,00%2,00%1,00%1,00%
Carbopol 974P1,00%1,00%1,00%--
Natrosol® 250 HHX---2,00%2,00%
Glycerin, USP/BP12,90%15,00%12,90%12,90%14,00%
Sorbic acid NF/European Pharmacopoeia0,08%0,80%0,08%0,08%0,08%
Methylhydroxybenzoate NF, European Pharmacopoeia0,18%0,18%0,18%0,18%0,18%
Purified water, USP, European Pharmacopoeia83,64%80,82%83,34%83,34%82,24%
In General100%100% 100%100%100%
Alternative dosage forms based on benzoyl peroxide
Benzoyl peroxide1,00%to 5.00%to 5.00%10,00%14,00%
Polycarbophil, USP2,00%2,00%1,00%2,00%2,00%
Carbopol 974P1,00%1,00%-1,00%1,00%
Natrosol® 250 HHX--2,00%--
Glycerin, USP/BP12,90%12,90%12,90%12,90%12,90%
Sorbic acid NF/European Pharmacopoeia0,08%0,08%0,08%0,08%0,08%
Methylhydroxybenzoate NF, European Pharmacopoeia0,18%0,18%0,18%0,18%0,18%
Purified water, USP, European Pharmacopoeia82,84%78,84%78,84%73,84%69,84%
In General100%100%100% 100%100%

The above dosage forms can be increased to increase to the maximum used a specific system for delivery. For example, it should be noted that the composition with 14% carbamide peroxide, as a rule, will apply with the regime doses, which requires less frequent introduction of the composition. In compositions with a high concentration of the low concentration of peroxide will be released over a longer period of time, minimizing the number of injections required per day or week.

All publications and patent applications mentioned in this specification, indicate the level of specialists in this field, which turned the invention. All publications and patent applications are incorporated here as a reference to the same extent as if individual publication or patent application was specifically and individually incorporated here by reference.

You must understand that the invention is not limited to the exact forms shown and described herein. Therefore, it is assumed that all rational modification achieved by the specialists in this field from the description, or normal experimentation will not depart from the essence and scope of the invention defined by the attached formula image is the shadow.

1. Pharmaceutical composition for treatment or prevention of vaginal infections, containing a peroxide source and bioadhesive Poperechnaya polymeric dosage form with prolonged release, where the composition is constructed in such a way that when its local introduction of the patient peroxide is released for at least 12 h in a quantity sufficient to increase the concentration of oxygen in the vagina and therapeutic reduction of vaginal pH, without any sterilization vaginal or without significant loss of normal desirable local microflora of the vagina.

2. The composition according to claim 1, where the synergistic mixture releases peroxide for at least 24 hours

3. The composition according to claim 2, where the specified dosage form with prolonged release contains bioadhesive swelling in water, water-insoluble cross stitched polycarboxylic polymer.

4. The composition according to claim 3 where the polymer is polycarbophil.

5. The composition according to claim 2, where the source of peroxide is in an amount of from about 0.01 to about 500 mg

6. The composition according to claim 4, where the source of peroxide is in an amount of from about 0.1 to about 75 mg

7. The composition according to claim 2, where the peroxide source is carbamide peroxide.

8. The composition according to claim 7, where the carbamide peroxide is in an amount of from about 0.01 to whom about 15% by weight.

9. The composition of claim 8, where the polymer is polycarbophil.

10. The composition according to claim 9, where the carbamide peroxide is in an amount of from about 0.1 to about 0.25 per cent.

11. The composition of claim 10 in the form of a single dosage form, where the composition is prepared for administration in an amount of from about 1 to about 2 g per dose.

12. The composition according to claim 2, where the synergistic mixture releases peroxide for at least 48 hours

13. The composition according to claim 3, where the synergistic mixture releases peroxide for at least 72 hours

14. The composition according to claim 2, where the amount of peroxide in the composition is in the range from 0,0035 to 350 mg

15. The composition according to 14, where the amount of peroxide is in the range from 0.01 to 100 mg

16. Pharmaceutical composition for treatment or prevention of vaginal infections, containing a peroxide source and bioadhesive Poperechnaya polymeric dosage form with prolonged release, where the composition is constructed in such a way that when its local introduction of the patient peroxide is released in a quantity of less than 0.1% by weight per hour, and the pH of the vagina therapeutically reduced without any sterilization vaginal or without significant loss of normal desirable local microflora of the vagina.

17. The composition according to item 16, where the specified dosage form with prolonged release includes bioadhesive swelling in water, water-insoluble cross stitched polycarboxylic polymer.

18. The composition according to 17, where the polymer is polycarbophil.

19. The composition according to p, where the source of peroxide is in an amount of from about 0.01 to about 500 mg

20. The composition according to claim 19, where the source of peroxide is in an amount of from about 0.1 to about 75 mg

21. The composition according to claim 20 in the form of a single dosage form, where the composition is prepared for administration in an amount of from about 1 to about 2.5 g per dose, and the amount of peroxide in the composition is in the range from 0.01 to about 100 mg

22. The composition according to item 21, where the amount of peroxide is in the range from about 0.1 to about 75 mg

23. The composition according to item 16, where the peroxide source is carbamide peroxide.

24. The composition according to item 23, where the carbamide peroxide is in an amount of from about 0.01 to about 15% by weight.

25. The composition according to 17, where a synergistic mixture releases peroxide for at least 24 hours

26. The composition according to p, where a synergistic mixture releases peroxide for at least 48 hours

27. Method for the treatment or prevention of vaginal infections, including the introduction of a vagina of the patient, in need of such treatment, a therapeutically effective amount of vaginal composition as defined in any one of claims 1, 3, 16, or 2.

28. Pharmaceutical composition for treatment or prevention of vaginal infections, containing a peroxide source and bioadhesive Poperechnaya polymeric dosage form with prolonged release, where the composition includes less than 0.1% by weight of peroxide and designed in such a way that when its local introduction of the patient, the concentration of oxygen in the vagina therapeutically increases, and the pH value of the vagina therapeutically reduced without any sterilization vaginal or without significant loss of normal desirable local microflora of the vagina.

29. The composition according to p where the specified dosage form with prolonged release contains bioadhesive swelling in water, insoluble in water poperechnyy polycarboxylic polymer.

30. The composition according to clause 29, where the polymer is polycarbophil.

31. The composition according to item 30, where the peroxide source is carbamide peroxide.

32. The composition according to p, where the peroxide is in an amount of from about 0,034 to about 0,085% by mass.

33. The composition according to p in the form of dosage forms, where the composition is prepared for administration in an amount of from about 1 to about 2.5 g per single dose.

34. The composition according to p, where the amount of peroxide is in the range from 0.01 to 100 mg

35. Composition according to claims 1, 16 or 28, where the peroxide source and bioadhesive the traveler Poperechnaya polymeric dosage form with prolonged release are in synergistically effective amounts.



 

Same patents:

FIELD: medicine; chemical and pharmaceutical industry.

SUBSTANCE: gel contains, mass %: active substance - enterosgel - 10.0, preservative agent - nipagin - nipazol (3:1) - 0.2, as base: carbopol gel 0.25% or CCMA 1% or Na-CMC 4% - remaining to 100.0.

EFFECT: expressed adsorbtion properties; convenient dozing and application.

9 ex, 1 tbl

Vaginal suppository // 2320319

FIELD: medicine, gynecology, pharmacy.

SUBSTANCE: invention relates to preparing vaginal suppositories containing laevomycetin and metronidazol as antibacterial components, pernisolon as an anti-inflammatory component, and cacao butter and lanolin as filling agents wherein these components are taken in the following ratio, g: laevomycetin, 0.25 ± 0.01; metronidazol, 0.25 ± 0.01; nystatin, 0.0625 ± 0.0025, or 250000 ± 10000 U; prednisolone, 0.003; cacao butter, 2 ± 0.2, and lanolin 0.05. Proposed suppository possesses the enhanced effectiveness against mixed infections of lower regions of female reproductive sphere and providing increasing remission period of disease.

EFFECT: improved and valuable medicinal properties of suppository, enhanced effectiveness of treatment.

1 tbl, 4 ex

Antibacterial agent // 2318523

FIELD: medicine, chemical-pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to an antibacterial agent as a suppository containing iodine and designated for treatment of inflammatory diseases of female genital region. Agent prepared as a suppository and containing iodine as an active substance and a filling agent comprises active substance as a complex of iodine-DMSO (dimethylsulfoxide) taken in the ratio = 1:(1-10) wherein it contains a fat-soluble base as a filling agent and wherein the content of iodine is 10 mg. Proposed suppository shows broad spectrum of antibacterial effect and without adverse effect. Active substance penetrates into deep tissues and shows selective effect on microorganisms. The claimed agent is suitable for using and it doesn't pollute skin and dress.

EFFECT: improved and valuable properties of agent.

5 cl, 2 tbl, 5 ex

FIELD: medicine, gynecology.

SUBSTANCE: the suggested therapy course should be carried out in three stages: during the first stage one should intravaginally and perorally introduce enterosorbent for 10 d, intranasally - thymogen for the period of about 10-14 d and, additionally, the first dosage of "SolkoTrichovac" vaccine. During the second stage the second dosage of vaccine and cycloferon liniment should be intravaginally introduced for 14 d. During the third stage the third dosage of vaccine should be applied along with euflorin B perorally and euflorin L intravaginally for 14 d. The innovation provides complex impact upon humoral body immunity and cell immunity of vaginal mucosa due to the three-stage scheme of introducing necessary preparations, optimizes the conditions for reconstructing resident vaginal microflora along with decreased intoxication and, thus, shortened number of relapses during a year.

EFFECT: higher efficiency of therapy.

1 ex, 2 tbl

FIELD: medicine, gynecology.

SUBSTANCE: the present innovation deals with the ways for applying the means of external application for preventing vaginal dysbacteriosis, in preparing the patients before gynecological manipulations. It is necessary to apply bacterial composition that normalizes vaginal microflora and contains lactose or lactulose and/or lactic or citric acid, a gel-forming agent, a moisturizing agent, a conservant and water at the following ratio of components, weight%: lactose or lactulose 25.00, not more; and/or lactic or citric acid 1.00, not more; a gel-forming agent 1.50, not more; a moisturizing agent 6.00-30.00, a conservant 0.30, not more; water - up to 100. The variant of vaginal composition can additionally contain: at least, one biologically active additive 0.01-2.00; an antiseptic component 0.50, not more. The innovation provides prophylaxis of vaginal dysbacteriosis due to normalizing the microflora of female reproductive organs; prolonged contact of this composition with mucosa additionally realizes regenerative, wound healing, protective, disinfective action; it, also, provides harmonization of intimate relations by removing unpleasant feelings during coitus due to the presence of moisturizing and lubricating action of the present composition.

EFFECT: higher efficiency of prophylaxis.

10 cl, 3 ex, 1 tbl

FIELD: medicine, gynecology.

SUBSTANCE: invention relates to a method for treatment of atrophic colpitis. Method involves using preparation "Triovit" that is administrated by oral route in the dose 2 capsules, 4 times per a day after eating with interval for 2.5-3 h for 1-2 months. Proposed method represents alternative for hormonal therapy.

EFFECT: improved method of treatment.

2 ex

FIELD: chemical-pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to a pantohematogen-base medicinal formulation for external using that comprises the following components, wt.-%: dry pantohematogen, 0.01-6; polymeric gel-forming composition, 0.1-20, and water, the balance. Proposed medicinal formulation provides using pantohematogen an aqueous solution without addition of alcohol and therefore it can be used in cases wherein alcohol-containing formulations are contraindicative - in burns of different degree, small skin damages and others and can be used in treatment of patients showing intolerance to alcohol-containing preparations. Method for preparing the pantohematogen medicinal formulation for external using involves preparing "dry" pantohematogen aqueous solution in the ratio limits pantohematogen : water = (1:50)-(1:200) by weight and solution is kept under normal conditions for 1 h and filtered. Additionally an aqueous solution of rare-linked polymer is prepared in the ratio = (1:10)-(1:200) and an aqueous solution of neutralizing agent in the amount necessary for providing slightly alkaline medium of final solution. In the volume ratio of pantohematogen aqueous solution and rare-linked polymer in the ranges = (3:1)-(1:10) components are mixed and stirred to obtain the homogenous solution. Then neutralizing agent aqueous solution is added to a mixture and stirred to obtain homogenous solution with slightly alkaline reaction (pH = 6-8). The advantage of proposed technology in preparing the medicinal formulation involves its simplicity and providing prolonged fitness period.

EFFECT: improved preparing method.

6 cl, 1 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to anhydrous, antifungal, lubricating gel compositions comprising polyhydric alcohol, gelatinizing agent and an antifungal azole compound, and to a method for treatment of a patient with fungal infections comprising administration of indicated composition in a patient. Compositions shows the excellent warming and lubricating effect after its applying on skin and mucosal tissues and provides the effective treatment of fungal infections.

EFFECT: improved and valuable properties of compositions.

21 cl, 2 tbl, 11 dwg, 9 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.

1 ex

FIELD: medicine; pharmacology.

SUBSTANCE: invention refers to new composition of antifungal and fungicidal action, and applied for treatment of diseases caused by bacterial and fungal infection. Composition of prolonged action contains active substances antibacterial (chlorhexidine 0.02-0.05 mass%), antifungal (clotrimasole - 0.4-0.6 mass%), dimexide (7.0-27.0 mass%) as potentiator intensifying penetration of active substances, and also the stabiliser based on polyvinyl alcohol solution in physiologic saline, and structurally represents polymeric matrix with immobilised active components made as gel or a film from which active components are gradually released during application.

EFFECT: invention provides reduction of treatments time for ENT-diseases and dermal diseases of both candidal and mixed aetiology.

3 cl, 1 tbl

FIELD: medicine; pharmacology.

SUBSTANCE: invention refers to new composition of antifungal and fungicidal action, and applied for treatment of diseases caused by bacterial and fungal infection. Composition of prolonged action contains active substances antibacterial (chlorhexidine 0.02-0.05 mass%), antifungal (clotrimasole - 0.4-0.6 mass%), dimexide (7.0-27.0 mass%) as potentiator intensifying penetration of active substances, and also the stabiliser based on polyvinyl alcohol solution in physiologic saline, and structurally represents polymeric matrix with immobilised active components made as gel or a film from which active components are gradually released during application.

EFFECT: invention provides reduction of treatments time for ENT-diseases and dermal diseases of both candidal and mixed aetiology.

3 cl, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and pharmaceutical industry, in particular to production of new treatment-and-preventive agent of antibacterial and spermicidal action which can be used in gynaecology. Offered treatment-and- preventive agent characterised by antibacterial and spermicidal action, is made as tablet for intravaginal introduction and contains chlorhexidine or its salt and base which as a main component contains lactose and other pharmaceutically acceptable adjuvant. Besides, specified agent can contain regenerant, in particular dexpanthenol or methyluracil or sea-buckthorn oil. Agent in the form of vaginal tablets is characterised by more effective antibacterial and spermicidal action and is more easy-to-use.

EFFECT: production of agent in the form of vaginal tablets characterised by antibacterial and spermicidal action.

40 ex, 10 tbl, 2 dwg, 2 cl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to chemical-pharmaceutical industry and concerns method of production of pharmaceutical composition containing N[(1-butyl-4-piperidinyl) methyl]-3,4-dihydro-2n -[1,3]oxazino[3,2]indole-10-carboxamide (SB 207266) piboserod or its pharmaceutically acceptable salt in combination with one or more pharmaceutically acceptable excipients, thus method includes formation of part or whole SB 207266 or its salts in granules by air-stream granulation. In invention there is also pharmaceutical composition offered which can be produced by air-stream granulation and/or which is produced by air-stream granulation. Declared invention enables to improve parameters of finished composition, and also to scale manufacture.

EFFECT: reception of a pharmaceutical composition with the improved parameters and possibility of its scale production process.

75 cl, 16 ex, 2 tbl, 4 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to chemical-pharmaceutical industry and concerns method of production of pharmaceutical composition containing N[(1-butyl-4-piperidinyl) methyl]-3,4-dihydro-2n -[1,3]oxazino[3,2]indole-10-carboxamide (SB 207266) piboserod or its pharmaceutically acceptable salt in combination with one or more pharmaceutically acceptable excipients, thus method includes formation of part or whole SB 207266 or its salts in granules by air-stream granulation. In invention there is also pharmaceutical composition offered which can be produced by air-stream granulation and/or which is produced by air-stream granulation. Declared invention enables to improve parameters of finished composition, and also to scale manufacture.

EFFECT: reception of a pharmaceutical composition with the improved parameters and possibility of its scale production process.

75 cl, 16 ex, 2 tbl, 4 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry and concerns composition, production method and application of agent based on perfluorcarbon-fat emulsions, used for blood substitute parenteral nutrition. Perfluorcarbon-fat emulsion composition can include one perfluorcarbon only, and mixed two, three or four perfluorcarbons: "ПФД" or "ПФТБА", either "ПФОБ", or "ПФМЦП", in ratio 1:1 to 10:10 and one oil selected of group: either soy, or cottonseed, or corn, olive oil, or cod-liver oil, and besides, can include sodium chloride, proxanole and/or phospholipids (soy or egg) as emulsifier; and in addition can contain either glycerol or sorbitol, or xylitol.

EFFECT: can be used for blood substitute parental nutrition.

96 cl, 13 ex, 1 dwg

FIELD: medicine.

SUBSTANCE: invention refers to medicine, specifically to urology and concerns prevention of urethra iatrogenic infection caused by transurethral manipulations. For this purpose 5 minutes prior to urinary tracts manipulation gel is introduced to urethra that contains 2 g of 10 % lydocaine solution per 100 g of glycerine. Before introduction gel is ozonised to ozone concentration 1200 mkg/l. Method provides effective prevention of urethra iatrogenic infection at absence of lydocaine by-effects.

EFFECT: provided effective prevention of urethra iatrogenic infection at absence of lydocaine by-effects.

2 ex

FIELD: medicine.

SUBSTANCE: invention concerns pharmaceutical composition resulted from sublimation drying in vacuum, containing oxalyplatine as an active component and pharmaceutically acceptable carrier containing as a carrier at least one alcoholic sugar of not-animal origin, thus mass ratio of oxalyplatine to alcoholic sugar of not-animal origin makes 1:3 to 1:7.

EFFECT: invention provides decreased risk of virus infection, especially animal cancellous encephalopathy agent.

5 cl, 4 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: invention refers to chemical pharmaceutical industry and concerns production of pharmaceutical composition of hypolipidemic and hepatoprotective activity. Composition contains statine or its pharmaceutically active salt, phospholipid of both vegetative and animal origin at total statine and phospholipid content 34-91.1 mass % and proportion 1:3 to 1:100, and base.

EFFECT: composition in various medicinal forms is characterised high efficiency, low by-effects, high hypolipidemic and hepatoprotective activity, thus allows treatment of active liver disease.

14 cl, 138 ex

FIELD: medicine.

SUBSTANCE: invention refers to chemical pharmaceutical industry and concerns production of pharmaceutical composition of hypolipidemic and hepatoprotective activity. Composition contains statine or its pharmaceutically active salt, phospholipid of both vegetative and animal origin at total statine and phospholipid content 34-91.1 mass % and proportion 1:3 to 1:100, and base.

EFFECT: composition in various medicinal forms is characterised high efficiency, low by-effects, high hypolipidemic and hepatoprotective activity, thus allows treatment of active liver disease.

14 cl, 138 ex

FIELD: medicine; pharmacology.

SUBSTANCE: invention concerns medicinal agent applied for various dermal diseases, injuries, stab, cut and septic wounds, burns and frostbites. Stated medicinal agent is antiseptic ointment containing iodophor as reactant, and polyethylene glycol as ointment base. As iodophor stated ointment contains pharmaiodine, and as ointment base - mixed polyethylene oxide-1500, polyethylene oxide-400 and glycerine taken in proportions as follows, (mass.%): pharmaiodine 5.0-20.0 (0.5-2.0 by active iodine); polyethylene oxide -1500 35-40; glycerine 15-17; polyethylene oxide-400 and other components to 100.

EFFECT: ointment is characterised by antiseptic, anti-inflammatory and wound healing action.

9 ex

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