Pharmaceutical composition for local application containing combination of fusidic acid and corticosteroid

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry and represents a pharmaceutical composition for local application containing fusidic acid within the range of 1 wt % to 5 wt % and mometasone within the range of 0.05 wt % to 2 wt % and a pharmaceutically acceptable carrier to be applied in treating or preventing inflammatory dermatoses caused by a secondary bacterial infection in a patient.

EFFECT: invention provides effective elimination of secondary bacterial infections in dermatologic injuries.

11 cl, 8 ex, 6 tbl

 

DETAILS PRIORITY

This patent application claims the priority of patent applications in India No. 1725/MUM/2007, filed September 10, 2007, the contents of which are fully incorporated into the present description by reference.

The technical FIELD of the INVENTION

The present invention relates to combination therapy antibiotic for local use and steroid for topical application for the treatment of inflammatory dermatoses associated with secondary bacterial infections. In particular, the present invention relates to pharmaceutical compositions for topical application containing a combination of fusidic acid fusidic acid) and corticosteroid such as mometasone furoate (Mometasone furoate), suitable for the treatment of infected eczema, such as secondarily infected dermatitis, including secondarily infected contact dermatitis, psoriasis, allergic contact dermatitis and atopic dermatitis with secondary bacterial infections of the skin. In particular, the present invention also relates to pharmaceutical compositions for topical application containing a combination of fusidic acid and corticosteroid such as mometasone furoate, suitable to prevent infection in cases of eczema, particularly atopic dermatitis in patients with risk of secondary bacterial infection.

p> In particular, the present invention also relates to pharmaceutical compositions for topical application containing a combination of fusidic acid and corticosteroid as halobetasol propionate, suitable for the treatment of infected sensitive to steroids dermatoses such as secondarily infected dermatoses, including secondarily infected contact dermatitis, allergic contact dermatitis, atopic dermatitis, psoriasis and other sensitive corticosteroid medicine (CRD) with secondary bacterial skin infections. In particular, the present invention also relates to pharmaceutical compositions for topical application containing a combination of fusidic acid and corticosteroid, such as halobetasol propionate, suitable to prevent secondary bacterial infections in patients with non-infected dermatoses.

The LEVEL of TECHNOLOGY

Bacteria, such as Staphylococcus, can live on many surfaces of the skin, not causing harm, but if the skin is punctured or damaged for any reason, bacteria-Staphylococcus can get inside and cause infection. The family of staphylococcal bacteria includes more than 30 species, and they can cause different kinds of diseases. But most staph infections are caused by species of Staphylococcus aureus (S. aureus) and Streptococcs pyogenes. Infections of skin and soft tissues are among the most common infections and can cause serious local and systemic complications. Bacterial infections are often observed in the defeat of eczema and atopic dermatitis. One of the most common infections of skin and soft tissues is the occurrence of secondary bacterial infection that causes complications of skin damage. Secondary bacterial skin infections are common complications of primary medicine, primary non-bacterial skin infections, traumatic injuries, ulcers, skin infections, parasites, and various other skin diseases. Despite differences in the cause and clinical presentation, open secondary bacterial infection with Staphylococcus aureus and Streptococcus pyogenes, or both of these species, is a widespread problem in patients with inflammatory skin diseases such as allergic contact dermatitis, atopic dermatitis or psoriasis. I believe that the cause of secondarily infected dermatitis (TYPE) are a variety of factors, including lack of expression of antimicrobial peptides on the skin, and the manifestation of the increased adhesion of Staphylococcus aureus to the skin of patients with atopic dermatitis. A serious consequence of atopic dermatitis, psoriasis and allergic the ski contact dermatitis is a violation of the integrity of the skin barrier. Recent studies of patients with atopic dermatitis showed that they reduced the levels of hydration of the epidermis and of the surface lipids of the skin, making the skin more susceptible to colonization by pathogens.

Was shown a correlation between the severity of eczema and S. aureus colonization, and it was found that bacterial colonization is an important factor in worsening the condition of skin damage. Staphylococcus aureus was detected on the skin of more than half of patients with chronic plaque psoriasis. It is shown that colonization by staphylococci and streptococci aggravate your psoriasis. Staphylococcal superantigen contribute to the pathogenesis of skin inflammation in atopic dermatitis through various possible mechanisms, namely direct stimulation of antigen-presenting cells and keratinocytes, stimulating the proliferation of T-cells by binding to receptors on T-cells), expansion of cutaneous lymphocyte antigen-positive T-cells. For the treatment of eczema and atopic dermatitis are widely used corticosteroids topical application, and some studies have shown the effect of the specified treatment on the bacterial flora of the skin.

Antibacterial agents, as for local applications, and system actions, in combination with corticosteroids for local use, mo the ut lead to a more rapid decrease in the colonization of S. aureus compared with monotherapy with corticosteroids for topical use. Corticosteroids are widely used for the treatment of eczema and atopic dermatitis. However, when the application or introduction of steroid stop, diseases easily recur, and if the steroid is used for a long time, it can cause several side effects such as atrophy of the skin and secondary infection. It was recently shown that bacterial superantigens induce insensitivity to corticosteroids. Therefore, the destruction of Staphylococcus aureus can lead to economies of steroid.

Leyden et al. (Br J Dermatol 1974; 90:525-30) first showed that therapeutic effect of antibiotics in combination with the steroid was better than the effect of steroid monotherapy. In some open or double-blind placebo-controlled trials of antimicrobial agents for local use and systemic antimicrobial agents were able to reduce colonization density and lead to a partial improvement in skin damage.

Larsen FS, et al. (Acta Derm Venereol. 2007;87 (1):62-8) suggested that the composition of fusidic acid and betamethasone-17-valerate as an option for short-term treatment of clinically infected atopic dermatitis.

M.A.Cobb (The Veterinary Journal Volume 169, Issue 2, March 2005, Pages 276-280) et al. conducted a study comparing double the th use of the drug, containing 0.5% fusidic acid and 0.1% betamethasone-17-valerate, and systemic therapy. This study showed no differences between these schemes and the fact that both of these regimens are effective treatment options for conditions such as acute moist dermatitis in dogs.

Strategos J. (Pharmatherapeutica. 1986; 4(9):601-6) proposed a comparative study of combination fozilova acid-betamethasone (fusidic acid betamethasone) and the combination of gentamicin-betamethasone (gentamicin-betamethasone).

In the patent US 6673783 owned by Leo Pharmaceutical Products Ltd, proposed connections, representing derivatives of fusidic acid. According to the invention also suggested that the combination of derivatives of fusidic acid with other therapeutically active components, such as penicillins, cephalosporins, tetracyclines, rifamycins, eritromicina, lincomycin, clindamycin, fluoroquinolones and corticosteroids.

In the application WO 2007051468 owned by Leo Pharma, the proposed pharmaceutical composition comprising crystalline guideway acid. According to the mentioned patent application also proposed compositions additionally contain other therapeutically active compound selected from the group comprising antibiotics and corticosteroids.

In the patent US 6127353, owned by Schering Corporation, proposed mometasone furoate mono is iDRAC and pharmaceutical compositions containing the specified connection.

In several clinical studies have confirmed the effectiveness of combination therapy of a powerful steroid for local use and antibiotic for topical use. Secondary bacterial infection can occur as a side effect in long-term therapy active steroids. These secondary bacterial infection also complicate the course of the initial inflammatory dermatoses, further increasing the amount of steroid required for their control. The benefits of local ways of antibiotic therapy include the ability to deliver a higher concentration of antibacterial agent to the skin than would be possible with systemic therapy. The specified application also allows, for the most part, to avoid severe systemic reactions.

However, in the above prior art was not disclosed a composition containing a combination of fusidic acid and corticosteroids, including mometasone or halobetasol. Therefore, there remains a need to develop drugs for topical application, containing a combination of fusidic acid and corticosteroids, including mometasone or halobetasol. According to the present invention proposed a pharmaceutical composition comprising a combination of fusidic acid and mometasone f is of roath, submitted new and a good basis for the treatment of inflammatory dermatoses associated with secondary bacterial infections. The authors of the present invention unexpectedly discovered that the antibiotic action of fusidic acid and anti-inflammatory corticosteroid, such as mometazon play an important role in the inhibition of S. aureus and reducing the severity of a patient's symptoms and signs of inflammatory skin infections. Preferably a combination of fusidic acid and mometasone furoate used for the treatment of inflammatory dermatoses associated with secondary bacterial infections, the effect mometasone directed to the treatment of dermatosis, and the action of fusidic acid is directed to the treatment of bacterial infections.

According to the present invention proposed a pharmaceutical composition comprising a combination of fusidic acid and halobetasol propionate. In several clinical studies have confirmed the effectiveness of combination therapy of a powerful steroid topical application and local antibiotic application. Secondary bacterial infection can occur as a side effect in long-term therapy powerful steroids. These secondary bacterial infection also complicate the course of inflammatory dermatoses, additional hydrocarbon is leciva number of steroid, required for control of these dermatoses. Staphylococcus aureus and Streptococcus pyogenes are the most common organisms that cause infectious inflammatory dermatoses, so the combination of halobetasol propionate and fusidic acid is a good basis for the treatment of inflammatory dermatoses associated with secondary bacterial infections, the effect of halobetasol propionate directed to the treatment of dermatosis, and the action of fusidic acid is directed to the treatment of a bacterial infection. The authors of the present invention unexpectedly discovered that the antibiotic action of fusidic acid and anti-inflammatory corticosteroid, such as halobetasol play an important role in the prevention of secondary bacterial infections in patients with non-infected dermatoses, as well as in the treatment of infected dermatoses sensitive to steroids, such as secondarily infected dermatoses, including secondarily infected contact dermatitis, allergic contact dermatitis, atopic dermatitis, psoriasis and other sensitive corticosteroid medicine (CRD) with secondary bacterial skin infections.

The PURPOSE of the INVENTION

The aim of the present invention is to provide pharmaceutical compositions for topical application, operasie combination antibiotic for local use and steroid for local use, for the treatment of inflammatory dermatoses associated with secondary bacterial infections. In particular, the present invention relates to pharmaceutical compositions for topical application containing a combination of fusidic acid and corticosteroid such as mometasone furoate, suitable for the treatment of infected eczema, such as secondarily infected dermatitis, including secondarily infected contact dermatitis, psoriasis, allergic contact dermatitis and atopic dermatitis with secondary bacterial infections of the skin. In particular, the present invention also relates to pharmaceutical compositions for topical application containing a combination of fusidic acid and corticosteroid such as mometasone furoate, suitable for prevention of infection in cases of eczema, particularly atopic dermatitis, patients with the risk of developing a secondary bacterial infection.

In particular, the present invention also relates to pharmaceutical compositions for topical application containing a combination of fusidic acid and corticosteroid, such as halobetasol propionate, suitable for the treatment of infected sensitive to steroids dermatoses such as secondarily infected dermatoses, including secondarily infected contact dermatitis, Allergy is a mini-contact dermatitis atopic dermatitis, psoriasis, and other sensitive corticosteroid medicine (CRD) with secondary bacterial skin infections. In particular, the present invention also relates to pharmaceutical compositions for topical application containing a combination of fusidic acid and corticosteroid, such as halobetasol propionate, suitable to prevent secondary bacterial infections in patients with non-infected dermatoses.

BRIEF description of the INVENTION

According to one variant of implementation of the present invention proposed a pharmaceutical composition for topical application in a suitable dosage form containing a combination of a therapeutically effective amount of an antibiotic, a therapeutically effective amount of a corticosteroid and a pharmaceutically acceptable carrier. Suitable dosage forms include aqueous or anhydrous semi-solid dosage forms such as creams, gels, ointments, lotions, and the like.

According to another implementation variant of the present invention proposed a pharmaceutical composition for topical application containing a combination of a therapeutically effective amount of the antibiotic agent such as fozilova acid, and a therapeutically effective amount kortiko is teroid, such as mometasone furoate or any other pharmaceutically acceptable salt/solvate mometasone, and a pharmaceutically acceptable carrier such compounds.

According to another implementation variant of the present invention proposed the use of pharmaceutical dosage forms for topical application, containing a combination of a therapeutically effective amount of the antibiotic agent such as fozilova acid, and a therapeutically effective amount of a corticosteroid such as mometasone furoate or any other pharmaceutically acceptable salt/solvate mometasone to treat infected eczema, such as secondarily infected dermatitis, including secondarily infected contact dermatitis, allergic contact dermatitis, psoriasis and atopic dermatitis with secondary bacterial skin infections.

According to another implementation variant of the present invention proposed the use of pharmaceutical dosage forms for topical application, containing a combination of a therapeutically effective amount of the antibiotic agent such as fozilova acid, and a therapeutically effective amount of a corticosteroid such as mometasone furoate or any other pharmaceutically acceptable salt/solvate mometasone approach is appropriate to prevent infection in cases of dermatitis, especially atopic dermatitis in patients with risk of secondary bacterial infection.

According to another implementation variant of the present invention proposed a pharmaceutical composition for topical application containing a combination of therapeutically effective amounts of the combination of (a) from 1 wt.% up to 5 wt.% fusidic acid; b) from 0.05 wt.% up to 2 wt.% mometasone furoate; and (c) pharmaceutically acceptable carrier.

According to another implementation variant of the present invention proposed the use of pharmaceutical dosage forms containing a combination of fusidic acid is present in the concentration range from 1 wt.% up to 5 wt.%, and mometasone furoate, which is present in the concentration range from 0.05 wt.% up to 2 wt.%, for the treatment of infected eczema, such as secondarily infected dermatitis, including secondarily infected contact dermatitis, allergic contact dermatitis and atopic dermatitis with secondary bacterial infections of the skin, or to prevent infection in cases of eczema, particularly atopic dermatitis in patients with risk of secondary bacterial infection.

According to another implementation variant of the present invention proposed a process for the manufacture of pharmaceutical dosage forms DL the local application, containing a combination of a) an effective amount of fusidic acid; and b) an effective amount of mometasone furoate; and (c) pharmaceutically acceptable carrier such compounds. Compositions for topical application according to the present invention contain mometasone furoate and guideway acid in a mass ratio ranging from 1:2.5 to 1:20.

Suitable dosage forms include aqueous and non-aqueous semi-solid dosage forms such as creams, gels, ointments, lotions, or any other dosage form suitable for topical application, and the like.

According to another implementation variant of the present invention proposed a pharmaceutical composition for topical application containing a combination of (a) a therapeutically effective amount of the antibiotic agent such as fozilova acid; b) a therapeutically effective amount of corticosteroid, such as halobetasol propionate or any other pharmaceutically acceptable salt/solvate of halobetasol; and (c) pharmaceutically acceptable carrier such compounds.

According to another implementation variant of the present invention proposed the use of pharmaceutical dosage forms for topical application, containing a combination of therapeutically effective if the ESCWA antibiotic agent, such as fozilova acid, and a therapeutically effective amount of corticosteroid, such as halobetasol propionate or any other pharmaceutically acceptable salt/solvate of halobetasol, for the treatment of infected sensitive to steroids dermatoses such as secondary infected dermatoses, including secondarily infected contact dermatitis, allergic contact dermatitis, atopic dermatitis, psoriasis, and other sensitive corticosteroid medicine (CRD) with secondary bacterial skin infections. According to another implementation variant of the present invention proposed the use of pharmaceutical dosage forms for topical application, containing a combination of a therapeutically effective amount of the antibiotic agent such as fozilova acid, and a therapeutically effective amount of corticosteroid, such as halobetasol propionate or any other pharmaceutically acceptable salt/solvate of halobetasol suitable to prevent secondary bacterial infections in patients with non-infected dermatoses.

According to another implementation variant of the present invention proposed a pharmaceutical composition for topical application containing a combination of therapeutically effective amounts of (a) from 1 wt.% to > = 5% fusidic acid; b) from 0.01 wt.% up to 2 wt.% halobetasol propionate; and c) a pharmaceutically acceptable carrier. Compositions for topical application according to the present invention contain halobetasol propionate and guideway acid in a mass ratio ranging from 1:2.5 to 1:100.

According to another implementation variant of the present invention proposed the use of pharmaceutical dosage forms for topical application, containing a combination of fusidic acid is present in the concentration range from 1 wt.% up to 5 wt.% and halobetasol propionate present in the concentration range from 0.01 wt.% up to 2 wt.%, for the treatment of infected sensitive to steroids dermatoses such as secondary infected dermatoses, including secondarily infected contact dermatitis, allergic contact dermatitis, atopic dermatitis, psoriasis, and other sensitive corticosteroid medicine (CRD) with secondary bacterial skin infections, or to prevent secondary bacterial infections in patients with non-infected dermatoses.

According to another implementation variant of the present invention proposed a process for the manufacture of pharmaceutical dosage forms for topical application, containing a combination of a) an effective amount of fusidic acid; (b) the EF is subjective number of halobetasol propionate; and c) a pharmaceutically acceptable carrier such compounds. Suitable dosage forms include aqueous and non-aqueous semi-solid dosage forms such as creams, gels, ointments, lotions, or any other dosage form suitable for topical application, and the like.

DETAILED description of the INVENTION:

Before to describe the present invention, it should be understood that this invention is not limited to a particular pharmacologically active carriers, formulations, treatment, and so forth, which can be changed. You should also understand that used in the present description, the terminology is given only to describe the specific implementation options, and it should not be considered as a constraint.

DEFINITIONS:

The term "therapeutically effective amount" or "effective amount" in the present description denotes any number of composition for topical application, which will cause a significant improvement in the condition of the disease when applied to the affected area. A single application may be sufficient, or it is also possible to apply the composition again within a certain period of time. The number can be changed depending on the condition to be treated, the degree of improvement condition is, and the type and concentration of the applied composition. According to the present invention antibiotic agent, such as fozilova acid, is present in the concentration range from 1 wt.% up to 5 wt.% of the total weight of the composition, and corticosteroid such as mometasone furoate, is present in the concentration range from 0.05 wt.% up to 2 wt.% of the total weight of the composition. According to the present invention antibiotic agent, such as fozilova acid, is present in the concentration range from 1 wt.% up to 5 wt.% of the total weight of the composition, and a corticosteroid, such as halobetasol propionate is present in the concentration range from 0.01 wt.% up to 2 wt.% of the total weight of the composition.

The terms "drug" and "pharmaceutical product" is also used interchangeably to refer to a pharmacologically active substance or composition.

The term "composition for local application or composition for topical application" means a composition in which a drug can be directly placed for application to the skin surface, and which is released effective amount of a medicinal product. These compounds may include creams, ointments, gels, lotions, or any other dosage form suitable for topical application, and the like. According to some of aspecto the above compositions can be applied to the skin in reocclusion form with additional bases, designs, or devices, or without them.

The term "skin" or "skin" is considered as including the outer part of the skin of a subject, comprising one or more layers of the epidermis, in which you can enter the pharmaceutical composition.

The term "treat" or "treatment" status, violation or condition, in the present description means: (1) prevent or delay the manifestation of clinical symptoms status, violation or condition developing in a mammal.

The term "eczema", also known as dermatitis, is a non-infectious skin disease characterized by itching and often accompanied by small blisters. It can be caused by a number of internal (endogenous) and external (exogenous) factors, and it may be acute or chronic. There are many types of eczema, it can represent or atopic dermatitis or contact dermatitis.

Atopic dermatitis is a chronic skin disease, the most common form of eczema, it is closely linked with asthma and hay fever, and can affect both children and adults, it can also be hereditary, and usually manifests in infancy or in early childhood. For a specified disease worsens after ingestion of certain foods or the donkey exposure to other allergens, such as pollen or dust. The most common symptoms include itching (or itching), dry skin, redness and inflammation. Constant scratching can also lead to cracking of the skin, making it prone to infections, and therefore, the damage caused by atopic dermatitis, frequent bacterial infections.

Contact dermatitis is a local reaction that includes redness, itching and burning. Contact dermatitis occurs when skin contact with allergens or irritants, resulting in either irritant contact dermatitis or allergic contact dermatitis. Irritant contact dermatitis is a direct irritation of the skin caused by direct chemical damage, which releases inflammatory mediators primarily of epidermal cells. Allergic contact dermatitis is a reaction of redness, itching, wetting that occurs when the skin comes into contact with a substance that the immune system recognizes as foreign, such as poison oak, sumac lacquer or sumac, which is developing, or some preservatives that are present in creams or lotions. This type of response reflects the specific sensitivity or Allergy to a certain substance. Due to violations of the barrier function of the skin there is predraspolozhennosti to secondary infection by bacteria; when infected eczema, the skin can crack and become wet (moist eczema).

The term "pharmaceutically acceptable", such as in the expression "pharmaceutically acceptable carrier" or "pharmaceutically acceptable salt/MES or derivative"means a compound that is not biologically or otherwise undesirable, i.e. the specified connection can be included in the composition for topical application according to the present invention and to enter the patient without causing any undesirable biological activity or interaction in an adverse manner with any of the other components of the composition that contains the specified connection.

The term "media" or "medium" in the present description refers to pharmaceutically acceptable substances-media suitable for the local introduction of medicines. Media and environment suitable for the present invention include any such substance known in this field, which are not toxic and do not interact with other components of the composition in an adverse manner.

"Fozilova acid" (fusidic acid) is a steroid antibiotic chemically related to cephalosporin P (cephalosporin P). The specified connection affects the transfer of amino acids from aminoacyl-RNA to protein of ribosome, inhibiting bacterial protein synthesis. Pointed to by the e connection may have a bacteriostatic or bactericidal depending on the concentration of the drug. Fozilova acid acts on gram-positive bacteria, particularly staphylococci, but almost no effect on gram-negative microorganisms. The specified connection also acts on streptococci (including pneumococcus) and Corynebacterium. The specified compound inhibits at least 99% resistant to oxacillin Staphylococcus aureus at a concentration of 2 mg/l, inhibited 100% sensitive to oxacillin Staphylococcus aureus at a concentration of 0.12 mg/l and inhibits 99% of Staphylococcus epidermidis in a concentration of 4 mg/L. Other bacteria, 90% of the organisms which, as shown, the said compound inhibits in a concentration of 2 mg/l or less, include: Peptococcus species, Clostridium species, Propionibacterium Danes, and most Bacteroides species. Monotherapy cream 2% fusidic acid or combination therapy (betamethasone, beclomethasone, ketoconazole and fusidate sodium) is effective in the treatment of secondary bacterial infections observed in dermatitis, pyoderma, boils, eczema, burns and psoriasis.

"Corticosteroids are a class of steroid hormones produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, the levels of electrolytes in the blood and behavior. Topical corticosteroids applies the Ute, to help relieve redness, swelling, itching and discomfort of many skin problems. These medicines are like cortisone. These medicines belong to the General family of medicines called steroids. You can apply steroid anti-inflammatory agents, including, but not limited to the above, corticosteroids, such as mometazon (mometasone), fluticasone (Fluticasone), clobetasol (Clobetasone), hydrocortisone (hydrocortisone), hydroxytriazine (hydroxyltriamcinolone), alpha metallicamatt (alpha-methyl dexamethasone, dexamethasone phosphate (dexamethasone-phosphate, beclomethasone dipropionate (beclomethasone dipropionate), alclometasone (alclometasone), clobetasol valerate (clobetasol valerate), desoximetasone (Desoximetasone), diflorasone (Diflorasone), fluotsinolon (Fluocinolone), fluocinonide (Fluocinonide), halobetasol (Halobetasol), desonide (desonide), hypertension acetate (desoxycorticosterone acetate, dexamethasone (dexamethasone), dichloride (dichlorisone), diflorasone diacetate (deflorasonediacetate), valerate (diflucortolone valerate), Platonov (fluadronolone), fluchloralin acetonide (fluclarolone acetonide), fludrocortisone (fludrocortisone), flumetazon pivalate (flumethasone pivalate), fluocinolone acetonide (fluosinolone acetonide), fluorine (fluocionide), fluocortin butyl ether (flucortine butylester), fluocortolone (fluocortolone), fluprednidene (fluprednidene) acetate (flupredidene (flupredylidene) acetate), flurandrenolide (flurandronolone), halcinonide (halcinonide, hydrocortisone acetate (hydrocortsone acetate), hydrocortisone butyrate (hydrocortisone butyrate), methylprednisolone (methylprednisolone), triamcinolone acetonide (triamcinolone acetonide), cortisone (cortisone), ortodoxo (cortodoxone), Platonic (flucetonide), fludrocortisone (fludrocortisone), diflorasone diacetate (difluorosone diacetate), flurandrenolide acetonide (fluradrenalone acetonide), Madison (medrysone), amlabel (amciafel), aminated (amcinafide), betamethasone (betamethasone) and esters of the compounds, chloroprednisone acetate (chlorprednisone acetate), clocortolone (clocortelone), krestinov (clescinolone), difluprednate (difluprednate), fluchloralin (flucloronide), flunisolide (flunisolide), fluorometholone (fluoromethalone), flaperon (fluperolone), fluprednisolone (fluprednisolone, hydrocortisone valerate (hydrocortisone valerate, hydrocortisone cyclopentylpropionate (hydrocortisone cyclopentylpropionate), hydrocortamate (hydrocortamate), meprednisone (meprednisone), paramethasone (paramethasone, prednisolone (prednisolone), prednisone (casino poker tournament), beclometasone (beclomethasone), triamcinolone (triamcinolone), and mixtures of these compounds. Preferably you can apply mometazon (mometasone) or halobetasol (halobetasol).

"Mometazon" (Mometasone), halogenated complex monoether, is a synthetic corticosteroid, which is highly effective and can show a lower incidence of side effects compared with other topical corticosteroids. Research conducted with cream mometasone 0.1 per cent, showed that this connection is in the middle range on the asset the spine, compared with other topical corticosteroids for topical use. Corticosteroids have multiple mechanisms of action including anti-inflammatory, immunosuppressive properties and antiproliferative action. Anti-inflammatory effect stems from low education, release, and activity of inflammatory mediators (e.g., kinins, histamine, liposomal enzymes, prostaglandins, leukotrienes), which reduces the initial manifestations of the inflammatory process. Corticosteroids inhibit boundary distance leukocytes and subsequent migration of cells into the injury area, and cancel the expansion and increased vascular permeability in this region, leading to reduced access of cells to the sites of damage. Specified vasoconstrictor effect reduces the radiolabeled serum, swelling and discomfort. Immunosuppressive properties to reduce the response to delayed and immediate hypersensitive reactions (e.g., type III and type IV). The specified action is a result of inhibiting the toxic effects of complexes of antigen and antibodies, which are deposited on the walls of blood vessels, creating a cutaneous allergic vasculitis, and inhibiting the action of lymphokines, target cells and macrophages, which together give reactions allergic contact der is of atita. Additionally, under the action of corticosteroids can also be prevented access sensitized T-lymphocytes and macrophages in target cells. Antiproliferative actions reduce hyperplastic tissue characteristics of psoriasis.

Like other corticosteroids for local use, mometasone furoate has anti-inflammatory, antipruritic and vasoconstrictive properties. The mechanism of anti-inflammatory action of steroids for topical use, in General, is unclear. However, I believe that corticosteroids act by inducing proteins, inhibiting phospholipase A2collectively called lipocortins. Under the action of phospholipase A2from membrane phospholipids released arachidonic acid. Argue that lipocortin control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid.

"Halobetasol" (Halobetasol), a synthetic corticosteroid, is structurally related to clobetasol (clobetasol), belongs to the category of highly active steroids. Halobetasol propionate, as shown in the test for the narrowing of blood vessels, is highly active corticosteroid for topical use in the compositions of solutions, creams and ointments. Like other Corti is asteroidal for local use, halobetasol propionate has anti-inflammatory, antipruritic and vasoconstrictive properties. I believe that corticosteroids act by inducing proteins, inhibiting phospholipase A2collectively called lipocortins. Studies on humans and animals have shown that less than 6% of the applied dose halobetasol propionate enters the blood circulation within 96 hours following topical application of the cream.

Halobetasol as steroid has multiple mechanisms of action including anti-inflammatory, immunosuppressive properties and antiproliferative action. Anti-inflammatory effect stems from low education, release, and activity of inflammatory mediators (e.g., kinins, histamine, liposomal enzymes, prostaglandins, leukotrienes), which reduces the initial manifestations of the inflammatory process. Corticosteroids inhibit boundary distance leukocytes and subsequent migration of cells into the injury area, and cancel the expansion and increased vascular permeability in this region, leading to reduced access of cells to the sites of damage. Specified vasoconstrictor effect reduces the radiolabeled serum, swelling and discomfort. Immunosuppressive properties to reduce the response to delayed and immediate Hypercom twitternya reaction (for example, type III and type IV). The specified action is a result of inhibiting the toxic effects of complexes of antigen and antibodies, which are deposited on the walls of blood vessels, creating a cutaneous allergic vasculitis, and inhibiting the action of lymphokines, target cells and macrophages, which together give reactions allergic contact dermatitis. Additionally, under the action of corticosteroids can also be prevented access sensitized T-lymphocytes and macrophages in target cells. Antiproliferative actions reduce hyperplastic tissue characteristics of psoriasis.

Compositions for topical application according to the present invention include compositions suitable for local, transdermal, rectal and transbukkalno (for example, sublingual) administration, etc., preferably the compositions according to the present invention is administered locally and made in the form of semi-solid dosage forms. Suitable dosage forms include aqueous or anhydrous semi-solid dosage forms such as creams, ointments, gels, lotions or any other dosage form suitable for topical application, and the like.

The term "water" in the present description means the presence in the composition of the water in the concentration range approx the RNO from 5% to 95%.

The term "anhydrous" in the present description means the presence in the composition of the water in the concentration range of less than 5%.

Compositions for topical application according to the present invention with mometazon and fusidic acid are suitable for the treatment of infected eczema, such as secondarily infected dermatitis, including secondarily infected contact dermatitis, allergic contact dermatitis, psoriasis and atopic dermatitis with secondary bacterial infections of the skin, or to prevent infection in cases of dermatitis, eczema, especially atopic dermatitis in patients with risk of secondary bacterial infection.

Compositions for topical application according to the present invention with halobetasol and fusidic acid are suitable for the treatment of infected sensitive to steroids dermatoses such as secondary infected dermatoses, including secondarily infected contact dermatitis, allergic contact dermatitis, atopic dermatitis, psoriasis, and other sensitive corticosteroid medicine (CRD) with secondary bacterial skin infections, or to prevent secondary bacterial infections in patients with non-infected dermatoses.

Compositions for topical application to implement the method of treatment according to the present image is the shadow you can enter from 1 to 6 times per day, and more usually from 2 to 4 times a day.

Pharmaceutical compositions for topical application according to the present invention may include suitable pharmaceutically acceptable carriers. A wide range of components includes: softening agents; emulsifiers, emulsion stabilizers and structure-forming agents; moisturizers; fragrances; preservatives; antioxidants, and chemical stabilizers; solvents; thickening agents, agents that increase rigidity, suspendresume agents; buffering agents, neutralizing substances and agents for regulating the pH; dyes, cloud emulsions, decolorizing agents, pigments; defoamers, agents that alter sensation on the skin, and the like. Typical softening agents include octyldodecanol, Caprile-capric triglyceride, castor oil, ceteareth-20, ceteareth-30, cetosteatil alcohol, ceteth 20, cetyl alcohol, cetylstearyl alcohol, cocoa butter, Diisopropylamine, glycerin, glycerylmonostearate, glycerylmonostearate, literallayout, isopropylmyristate, isopropyl, lanolin, lanolin alcohol, hydrogenated lanolin, liquid paraffin, linoleic acid, mineral oil, oleic acid, petrolatum, polyethylene glycol, ethers of polyoxyethyleneglycol and fatty alcohols, polyoxypropylene-15-stearyl ether, propilenglikolstearat, impregnated englishliterature, squalane, steareth-2 or steareth-100, stearic acid, stearyl alcohol, urea and the like. Typical emulsifiers include propilenglikolstearat, aluminum starch octenylsuccinate, ammonium hydroxide, amphoteric-9, beeswax, bleached beeswax, synthetic wax, carbomer 934, carbomer R, carbomer 940, ceteareth-20, ceteareth-30, Cetearyl alcohol, ceteth 20, cetyl alcohol, cholesterol, cyclomethicone, diglycerides, Dimethicone (for example, Dimethicone 350), disodium, monooleate sulfosuccinate, emulsifying wax NF, esters of pentaerythritol and fatty acids, glycerides, glycerylmonostearate, glycerylmonostearate, literallayout, lanolin, lanolin alcohol, hydrogenated lanolin, magnesium stearate, mineral oil, monoglycerides, polyethylene glycol, PEG stearate, polyethylene glycol 6000 distearate, polyethylene glycol-1000-monocationic ether, polyethylene-glycol monostearate, polyethylene glycol 400 monostearate esters of polyoxyethyleneglycol and fatty alcohols, polyoxyethyleneglycol 20 cetosteatil ether, polyoxyethyleneglycol 40 stearate, Polysorbate 20, Polysorbate 40, Polysorbate 60, Polysorbate 80, Polysorbate, GPR-25 oleate, propilenglikolstearat, quaterni-15, simethicone, sodium Laureth sulphate, sodium lauryl sulfate, esters sorbitan, sorbitanoleat, servicemanual, servicemanagement, with buitenveldert, sorbitanoleat, servicesecurity, steareth 2 steareth-100, stearic acid, stearyl alcohol, triethanolamine, trolamine and the like. Typical stabilizers of emulsions and structure-forming agents include carbomer 934, carbomer R, carbomer 940, Cetearyl alcohol, cetosteatil alcohol, cetyl alcohol, cetylstearyl alcohol, dextrin, diglycerides, edetate disodium, glycerides, glycerylmonostearate, literallayout, hydroxypropylcellulose, monoglycerides, plasticized hydrocarbon gel, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 1450, polyethylene glycol 8000, polyethylene glycol, propilenglikolstearat, stearyl alcohol and the like. Typical humectants include glycerin, propylene glycol, sorbitol, urea, and the like. Typical odorants include hypoallergenic fragrant substance, menthol, and the like. Typical preservatives, antioxidants, and chemical stabilizers include alcohol, benzyl alcohol, bottled hydroxyanisol, bottled hydroxytoluene, butylparaben, calcium acetate, castor oil, chlorocresol, sodium sorbate, 4-chloro-m-cresol, citric acid, edetate disodium, Dowicil 200 (Dow), ethoxylated alcohol, ethyl alcohol, glycerin, Glydant Plus (Lonza), 1,2,6-hexanetriol, Kathon CG (Rohm & Haas, Liquid Germall Plus (ISP Sutton Labs), Liquipar (ISP Sutton Labs), methylparaben, parab the HN, potassium sorbate, propylgallate, propylene glycol, propylparaben, sodium bisulfite, sodium citrate, sodium metabisulfite, sorbic acid, tannic acid, triglycerides of saturated fatty acids, Ucarcide (Union Carbide), vitamin E, zinc stearate, and the like. Typical solvents include alcohol, castor oil, Diisopropylamine, ethoxylated alcohol, citrate, fatty alcohol, glycerol, 1,2,6-hexanetriol, hexyleneglycol, isopropyl alcohol, isopropylmyristate, isopropyl, mineral oil, phosphoric acid, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 1450, polyethylene glycol 8000, polyethylene glycol 1000 monocationic ether, polietilenglikolmonostearat, polyethylene glycol 400 monostearate, polyethylene glycols, polyoxyethyleneglycol 20 cetosteatil ether, polyoxypropylene 15-stearyl ether, Polysorbate 20, Polysorbate 40, Polysorbate 60, Polysorbate 80, Polysorbate, octyldodecanol, propylene carbonate, propylene glycol, purified water, SD alcohol 40, triglycerides of saturated fatty acids, and the like. Typical thickening agents, hardening agents and suspendresume agents include aluminum stearate, beeswax, bleached beeswax, synthetic wax, carbomer 934, carbomer R, carbomer 940, cetosteatil alcohol, cetyl alcohol, wax atilovykh ester, dextrin, glitzer monostearate, hydroxypropylcellulose, kaolin, paraffin, white soft paraffin, petrolatum, white petrolatum, polyethylene, propilenglikolstearat, starch, stearyl alcohol, wax, white wax, xanthan gum, bentonite, and the like. Typical buffering agents, neutralizing agents and substances that regulate pH, include phosphoric acid, ammonium hydroxide, citric acid, diisopropanolamine, hydrochloric acid, lactic acid, monobasic sodium phosphate, sodium citrate, sodium hydroxide, sodium phosphate, triethanolamine, trolamine and the like. Typical cloud emulsions/dyes include suitable for using agents that may be organic and/or inorganic, and the like. Suitable examples include titanium dioxide and pre-dispersed titanium dioxide. Typical defoamers include cyclomethicone, Dimethicone (for example, Dimethicone 350), simethicone, and the like. Typical agents that alter sensation on the skin include aluminum starch octenylsuccinate (gamma rays), and the like.

Hereinafter the present invention will be illustrated in the following examples, and should not be limited presents compositions. Specialist in the art will easily be able to determine the composition for other dosage forms, and to substitute equivalent fillers is as specified in the present description or known in this field.

Example 1: a Composition for topical application with mometasone-furoate and fusidic acid
StageComponentswt.%
IClarified soft paraffin63,869
Bleached beeswax5,000
Promulgen G™7,000
The propilenglikolmonostearata8,000
Aluminum starch octenylsuccinate5,000
(Dry Pure Flow™)
IIPurified water3,000
Hexyleneglycol6,000
Phosphoric acid (10 wt./vol.%)*
Mometasone furoate, micronized0,100
Fozilova acid (micronized)2,000
*the amount needed to bring the pH of the solution hexyleneglycol in water up to pH values of 4.0

A brief description of the production process

1. Preparation of the oil phase. Clarified soft paraffin, bleached beeswax, Promulgen G™, propilenglikolmonostearata, aluminum starch octenylsuccinate (Dry Pure Flow™) was heated to a temperature in the range 70-72°C.

2. The medicinal preparation phase: the pH of the solution hexyleneglycol in water brought to a pH of 4.0 using phosphoric acid. The resulting solution was heated to a temperature from 70°C to 72°C. To the specified solution was added mometasone furoate and guideway acid and dissolved with stirring.

3. Emulsification: drug phase was added to the oil phase under stirring, maintaining the temperature from 70°C to 72°C and then homogenized for 10 minutes. After homogenization of the mixed phase was slowly cooled, getting cream for local application from white to not-quite white.

Example 2: a Composition for topical application with mometasone-furoate and fusidic acid
StageComponentswt.%
IClarified soft paraffin6,000
Liquid paraffin6,000
Bleached beeswax1,500
Promulgen G4,000
The propilenglikolmonostearata2,000
Polysorbate 601,500
Cetosteatil alcohol6,000
Bottled hydroxytoluene (EIT)0,050
Bottled hydroxyanisol (BHA)0,050
IIPurified water 46,569
IIIPurified water1,000
Potassium sorbate0,200
IVPhenoxyethanol0,500
VPurified water5,000
Polysorbate 600,500
Glycerin8,000
Fozilova acid2,000
VIPurified water3,000
Hexyleneglycol6,000
The solution of phosphoric acid (10%)*
Mometasone furoate0,100
*the amount needed to bring the pH of the solution hexyleneglycol in water up meant what I pH 4,0, and then to bring the final pH

A brief description of the production process

1. Preparation of oil phase: clarified soft paraffin, liquid paraffin, bleached beeswax, Promulgen G™, propilenglikolmonostearata, Polysorbate 60, cetosteatil alcohol was heated to a temperature in the range 70-72°C. was Added bottled hydroxytoluene and bottled hydroxyanisol.

2. Preparation of aqueous phase: purified water was heated to a temperature in the range 70-72°C.

3. Phase emulsification adding the oil phase to the aqueous phase at a temperature from 70°C to 72°C and homogenized for 15 minutes.

4. Phase mometasone furoate: brought the pH of the solution hexyleneglycol in water to pH of 4.0 using phosphoric acid, and then heated to a temperature in the range 70-72°C. Mometasone furoate was dissolved under stirring. Solution was added drugs mometasone furoate to the emulsified phase at 70°C.

5. Phase fusidic acid get purified water and glycerin, and added to them Polysorbate 60. Was dispersively guideway acid under stirring. Solution was added fusidic acid to the emulsified phase at 70°C.

6. Added pre-dissolved potassium sorbate to total at 40°C and stirring.

7. Added Phenoxyethanol to total at 40°C, paramasivan is I. Then the total volume was slowly cooled with stirring, getting the cream.

Certain physical parameters:

Description: cream white

pH: 5.0-5.5

Example 3: Composition for local application with mometasone-furoate and fusidic acid
StageComponentswt.%
IClarified soft paraffin6,000
Light liquid paraffin6,000
Sorbitan the monostearate (SMS)2,000
Polyoxyl 20 cetyl ether ( Brij 58)2,000
Cetosteatil alcohol8,000
Bleached beeswax3,000
Bottled hydroxyanisol (BHA)0,050
Bottled hydroxytoluene (EIT)0,050
IIPurified water52,069
Glycerin8,000
IIIPurified water1,000
Potassium sorbate0,200
IVPhenoxyethanol0,500
VPurified water3,000
Hexyleneglycol6,000
Phosphoric acid (10 wt./vol.%)*
Mometasone furoate0,100
Fozilova acid2,000
*the amount needed to bring the pH of the solution hexyleneglycol in water up to pH 4.0, and then to bring the end is N

A brief description of the production process

1. Preparation of oil phase: clarified soft paraffin, light liquid paraffin, servicemonitor, polyoxyl 20 cetyl ether (Polyoxyl 20 Cetyl Ether), cetosteatil alcohol, bleached beeswax was heated to a temperature in the range 70-72°C. was Added bottled hydroxytoluene and bottled hydroxyanisol.

2. Preparation of aqueous phase: a mixture of purified water and glycerin was heated to a temperature in the range 70-72°C.

3. Phase emulsification adding the oil phase to the aqueous phase at a temperature from 70°C to 72°C and homogenized for 15 minutes.

4. The medicinal preparation phase: the pH of the solution hexyleneglycol in water brought to a pH of 4.0 using phosphoric acid. The resulting solution was heated to a temperature from 70°C to 72°C. To the specified solution was added mometasone furoate and guideway acid and dissolved with stirring. Then the resulting solution was added to the emulsified phase at 70°C.

5. Added pre-dissolved potassium sorbate to total at 40°C and stirring.

6. Added Phenoxyethanol to total at 40°C and stirring. Then the total volume was slowly cooled with stirring, getting the cream.

Physical parameters:

Description: cream white

pH: 5.0-5.5

Example 4: Composition for local application with halobetasol propionate and fusidic acid
StageComponentswt.%
IClarified soft paraffin4,000
Polyoxyl 20 cetyl ether (Brij 58)1,800
Cetyl alcohol2,000
Cetosteatil alcohol8,000
Dimethicone 3500,500
Isopropyl5,500
Bottled hydroxytoluene (EIT)0,100
Phenoxyethanol0,700

IIPurified water58,626
Potassium sorbate0,200
IIIGlycerin2,000
Polyoxyl 20 cetyl ether (Brij 58)0,050
Water0,750
Halobetasol propionate0,050
IVGlycerin6,000
Polyoxyl 20 cetyl ether (Brij 58)0,200
Purified water7,000
Fozilova acid2,000
VThe solution of phosphoric acid 10%0,524

A brief description of the production process

1. Preparation of oil phase: clarified soft paraffin, part of polyoxyl 20 cetyl ether, cetyl alcohol, cetosteatil alcohol, Dimethicone 350, isopropyl imitat, bottled hydroxytoluene and Phenoxyethanol was heated to a temperature in the range 70-72°C.

2. Preparation of aqueous phase: potassium sorbate was dissolved in water and heated to a temperature in the range 70-72°C.

3. Emulsification: added the oil phase to the aqueous phase at a temperature from 70°C to 72°C and homogenized for 15 minutes, then cooled.

4. Glycerol was heated to 60°C, then added, completely melting, polyoxyl 20 cetyl ether (Brij 58), then added water to maintain the temperature from 40°C to 42°C. At 42°C was added under stirring, fully dispersive, halobetasol propionate.

5. Heated glycerin to 60°C, then added, completely melting, polyoxyl 20 cetyl ether (Brij 58), then added water to maintain the temperature from 40°C to 42°C. At 42°C was added under stirring, fully dispersive, fusicology acid.

6. Solution was added halobetasol to total at 50°C and stirring.

7. Solution was added fusidic acid to total at 40°C and stirring.

8. Added a 10% solution of phosphoric acid to total at 40°C and stirring. Then the total volume was slowly cooled with stirring, getting the cream.

Physical parameters:

Description: cream white

the pH at 25°C: from 4.5 to 6.0

Example 5: a Composition for topical application to halobetasol propionate and fusidic acid
StageComponentswt.%
IClarified soft paraffin4,000
Polyoxyl 20 cetyl ether (Brij 58)1,800
Cetyl alcohol2,000
Cetosteatil alcohol8,000
Dimethicone 3500,500
Isopropyl5,500
Bottled hydroxytoluene (EIT)0,100
Benzyl alcohol : 1,000
IIPurified water63,320
Potassium sorbateIIIGlycerin2,000
Polyoxyl 20 cetyl ether (Brij 58)0,050
Water0,750
Halobetasol propionate (micronized)0,050
IVGlycerin6,000
Polyoxyl 20 cetyl ether (Brij 58)0,200
Purified water2,000
Fozilova acid (micronized)2,000
VThe solution of phosphoric acid 10%0,530

A brief description of the production process

1. Preparation of oil phase: clarified soft paraffin, part of polyoxyethyleneglycol 20 cetyl ether, cetyl alcohol, cetosteatil alcohol, Dimethicone 350, isopropyl and benzyl alcohol was heated on the temperature in the range 70-72°C.

2. Preparation of aqueous phase: potassium sorbate was dissolved in water and heated to a temperature in the range 70-72°C.

3. Emulsification: added the oil phase to the aqueous phase at a temperature from 70°C to 72°C and homogenized for 15 minutes, then cooled.

4. Glycerol was heated to 60°C, then added, completely melting, polyoxyl 20 cetyl ether (Brij 58), and added water to maintain the temperature from 40°C to 42°C. At 42°C was added under stirring, fully dispersive, halobetasol propionate.

5. Heated glycerin to 60°C, then added, completely melting, polyoxyl 20 cetyl ether (Brij 58), and added water to maintain the temperature from 40°C to 42°C. At 42°C was added under stirring, fully dispersive, fusicology acid.

6. Solution was added halobetasol to total at 50°C and stirring.

7. Solution was added fusidic acid to total at 40°C and stirring.

8. Added a 10% solution of phosphoric acid to total at 40°C and stirring. Then the total volume was slowly cooled with stirring, getting the cream.

Example 6: a Composition for topical application to halobetasol propionate and fusidic acid
StageThe components of the coefficients wt.%
IClarified soft paraffin4,000
Polyoxyl 20 cetyl ether (Brij 58)2,000
Cetyl alcohol2,000
Cetosteatil alcohol8,000
Dimethicone 3500,500
Isopropyl6,000
Bottled hydroxytoluene (EIT)0,100
Benzyl alcohol : 1,000
IIPurified water63,350
IIIDiethylene monotropy ether (Transcutol P)1,000
Halobetasol propionate0,050
IVHexyleneglycol5,000
Glycerin4,000
Polysorbate 60 (tween 60)1,000
Fozilova acid2,000

A brief description of the production process

1. Preparation of oil phase: clarified soft paraffin, polyoxyl 20 cetyl ether, cetyl alcohol, cetosteatil alcohol, Dimethicone 350, isopropyl, BHT and benzyl alcohol was heated to a temperature in the range 70-72°C.

2. Preparation of aqueous phase: water was heated to a temperature in the range 70-72°C.

3. Emulsification: added the oil phase to the aqueous phase at a temperature from 70°C to 72°C and homogenized for 15 minutes, then cooled.

4. In a separate container was placed diethylene monotropy ether (Transcutol P) was added thereto under stirring of halobetasol propionate. Continued to stir for 5 minutes for complete dissolution and added to the total volume at 50°C and stirring.

5. Heated exrension to 50°C, then add the glycerin and Polysorbate 60 (tween 60) and maintained a temperature in the range 50°C-52°C. N and 52°C was added under stirring, fully dissolving, fusicology acid. Solution was added fusidic acid to the basic total at 40°C and stirring. Then the total volume was slowly cooled with stirring, getting the cream.

Example 7: Composition for local application with halobetasol propionate and fusidic acid
StageComponentswt.%
IClarified soft paraffin9,000
Cetosteatil alcohol10,000
Liquid paraffin7,000
Polysorbate 60 (tween 60)2,000
Vitamin E (as dl-alpha-tocopherol acetate)0,050
Bottled hydroxytrol0,050
IIPurified water57,580
Potassium sorbate0,270
IIIDiethylene monotropy ether (Transcutol P)1,000
Halobetasol propionate0,050
IVGlycerin10,000
Polysorbate 60 (tween 60)1,000
Fozilova acid2,000

A brief description of the production process

1. Preparation of oil phase: clarified soft paraffin, cetosteatil alcohol, liquid paraffin, Polysorbate 60, vitamin E and bottled hydroxytrol was heated to a temperature in the range 70-72°C.

2. Preparation of aqueous phase: potassium sorbate was dissolved in water and heated to a temperature in the range 70-72°C.

3. Emulsification: added the oil phase to the aqueous phase at a temperature from 70°C to 72°C and homogenized for 15 minutes, then cooled.

4. In a separate container was placed diethylene monotropy ether (Transcutol P) was added thereto under stirring of halobetasol propionate. Cont is whether to mix for 5 minutes for complete dissolution and added to the total volume at 50°C and stirring.

5. Heated glycerin and Polysorbate 60 (tween 60), 50°C, then added, fully dispersive, fusicology acid. Added a dispersion of fusidic acid to total at 40°C and stirring. Then the total volume was slowly cooled with stirring, getting the cream.

Example 8: Composition for local application with halobetasol propionate and fusidic acid
StageComponentswt.%
ICetyl alcohol12,000
Isopropyltoluene (Prisorin 2021)3,000
Isopropyl2,000
Polyoxyl 20 cetyl ether (Brij 58)2,000
Of polyoxyethylene (21) stearyl ether (Brij 721)3,000
IIPurified water56,663
III Purified water5,000
Kidmodeling0,200
IVPurified water3,000
The combination & Methylchloroisothiazolinone (Kathon CG)0,050
VGlycerin8,000
Polyoxyl 20 cetyl ether (Brij 58)1,000
Fozilova acid (micronized)2,037
VIGlycerin2,000
Halobetasol propionate (micronized)0,050
Total100,000

A brief description of the production process

1. Preparation of oil phase: heated cetosteatil alcohol, isopropyltoluene, polyoxyl 20 cetyl ether (Brij 58), polyoxyethylene (21) stearyl ether (Brij 721)was heated to a temperature in the range 70-72°C.

2. Preparation of aqueous phase: part of water was heated to a temperature in the range 70-72°C.

3. Emulsification: added the oil phase to the aqueous phase at a temperature from 70°C to 72°C and homogenized for 15 minutes, then cooled.

4. Added to the total volume of the solution imagemotion in water at 40°C-42°C and stirring.

5. Added to total variance Kathon CG at 40°C-42°C and stirring.

6. Heated glycerin and polyoxyl 20 cetyl ether (Brij 58), 50°C, then added, fully dispersive, fusicology acid. Added a dispersion of fusidic acid to total at 40°C and stirring.

7. In a separate container was placed glycerin was added thereto under stirring of halobetasol propionate. Continued to stir for 5 minutes for complete dissolution and added to the total volume at 40°C and stirring. Then the total volume was slowly cooled with stirring, getting the cream.

Compositions according to the present invention, Examples 1 and 4, were investigated on clinical efficacy for the people-the volunteers at the readings according to the present description.

The composition according to the present invention were evaluated for efficacy, safety and tolerability of the combined cream mometazon 0.1 wt.% plus fozilova acid 2 wt.%, Example 1, compared to cream mometasone 0.1 wt.%, for predator is of secondary bacterial infections in patients with dermatoses, sensitive to corticosteroids. Combined drug mometasone and fusidic acid according to the present invention was compared with a commercially available drug Momate®containing 0.1 wt.% mometasone furoate shipped to India, Malaysia and the Philippines firm Glenmark Pharmaceutical Ltd.

A prospective, randomized, multicenter, open study was performed on 50 patients, male and female (post-menopausal age, undergone surgical sterilization, or use a reliable method of contraception) at the age from 12 to 65 years. The duration of the study was 3 weeks, including a 2-week period of active treatment with preliminary 1-week washout phase. The selected patients were clinically diagnosed sensitive to corticosteroid dermatitis with secondary bacterial infections. Exclusion criteria patients were pregnancy and lactation, serious skin diseases, pigmentation disorders and extensive scarring in the affected areas, hypersensitivity to mometazon or fusidic acid, or a cream Foundation, state of impaired immunity, patients with common infections, patients who participated in studies of new drugs in the last 6 months, patients with serious illnesses ser is CA, liver, kidney or brain vessels, a malignant tumor, chronic uncontrolled systemic diseases, such as diabetes, hypertension, asthma, collagen, etc. or other serious medical conditions.

Plan research
Action/observationScreeningVisit IVisit IIVisit III
visit (Day 7)(origin / Day 0)(Day 6-7)(Day 13-14)
Demographic dataX
The patient's history and medical examinationX
Criteria for inclusion/exclusionX
Informed consent X
Clinical evaluationXXXX
Laboratory and other studiesX
The introduction of an investigational medicationXXX
Side effectsXXX
The compliance of patients treatmentXX
General assessment of effectivenessXX
Bacteriological examinationXX

Screening visit:

Recorded demographic data and medical history of the patients, and conducted a brief medical examination. Patients were recruited on the basis of the criteria of inclusion and exclusion. Received written informed consent from selected patients. During this visit conducted clinical assessment before the examination, laboratory studies, chest x-ray and ECG. Patients underwent a 1-week washout period, after which he began the study treatment.

The estimated parameters of clinical effectiveness:

The present study was carried out in such a way as to observe clinical signs and symptoms such as peeling, erythema, pruritus, induration/swelling, pain, exudation/scum formation, and the amount of signs/symptoms. Additionally watched the severity of the lesions, discharge from the lesions, the results of bacteriological tests and the results of bacteriological tests, including Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus spp Enterobacteriaceae.

Investigational treatment

Patients received the cream mometazon 0,1% plus fozilova acid 2%, applied to the affected area/area twice a day in a thin layer, with careful and complete rubbing, and each application separated by intervals of about 12 hours.

Full General the valuation of effectiveness

At the end of the study performed a full evaluation of the effectiveness of the drug as a researcher and patient.

The overall score therapist included the following parameters:

ScoreScore
1Complete recovery (100% remission of signs and symptoms)
2Excellent (90-99% improvement)
3Good (75-89% improvement)
4Moderate (50-74% improvement)
5Weak (30-49% improvement)
6No improvement (0-29%)
7Worse than (<0%)

General assessment of the patient

ScoreScore
1Much better
2Somewhat better
3As well
4 Worse
5Much worse

The compliance of patients to treatment was assessed at visits II, III and IV by direct questioning of the patients.

The results of the study:

Collected research data to assess the effectiveness of the combined cream mometasone 0.1 wt.% and fusidic acid 2 wt.% (Example 1 of the present invention) compared with cream mometasone 0.1 wt.%, Momate®, to prevent secondary bacterial infections in patients sensitive to corticosteroid dermatitis, and analyzed the resulting data using nonparametric criterion. All criteria were bilateral, took a significance level of p<0,05.

Table 1 shows that at the beginning of the countdown average scores in patients receiving treatment composition according to Example 1 of the present invention, and in patients receiving treatment cream Momate®amounted to 2.25 and 2,60 respectively, that is was the same, and the difference was not statistically significant. After treatment, the average score in the group of Example 1 decreased by 78.6 per cent, which was significantly higher compared to 61.2% of group Momate®. After treatment, the average score for erythema among patients treated according to Example 1 of this izaberete the Oia, fell to 83.7%, which was significantly longer compared with 58.3% of group Momate®. After treatment, the average score for itching in the group of Example 1 decreased by 75.3%, which was significantly longer compared with 57.4% for the group Momate®. After treatment, the average score for sealing/swelling in a group of Example 1 decreased by 80.6%, which was significantly higher compared to 52.5 per cent for the group Momate®. After treatment, the average score for pain in a group of Example 1 decreased by 82.4%, which was significantly higher compared to 61.2% of group Momate®. After treatment, the average score for exudation in the group of Example 1 decreased by 76,2%, which was significantly more as compared to 56.4% of group Momate®. After treatment, the average score for the sum of signs/symptoms in a group of Example 1 decreased 79.6%, which was significantly more as compared to 58.1% for group Momate®.

Table 2: Results of changes in the severity of lesions for the combined cream mometasone 0.1 wt.% and fusidic acid 2 wt.% (Example 1 of the present invention) compared with cream mometasone 0.1 wt.%, Momate®, to prevent secondary bacterial infections in patients sensitive to corticosteroid medicine
Table 2 Changes in severity of lesions between the two groups
Example 1Momate®
weightorigin (N=25) No.%day 6-7 (N=25) No.%day 13-14 (N=25) No.%origin (N=26), No.%day 6-7 (N=26) No.%day 13-14 (N=26) No.%
light05 (20,0)08 (32,0)*22 (88,0)06 (23,1)07 (26,9)12 (46,2)
moderate10 (40,0)12 (48,0)02 (08,0)09 (34,6)11 (42,3)09 (34,6)
heavy10 (40,0)05 (20,0)01 (04,0)11 (42,3)08 (30,8)05 (19,2)
The Chi-square
*P<0,05 significant

In this is the study in both groups at the start of the observed severity of lesions from mild to moderate in 72,1-80.0% of all cases. After treatment in the group of Example 1 in 88,0% of all cases were observed light the severity of the lesions that were significantly low compared with 46.2% in the group Momate®.

Table 3:
Results changes in discharge from the lesions for combined cream mometasone 0.1 wt.% and fusidic acid 2 wt.% (example 1 of the present invention) compared with cream mometasone 0.1 wt.%, Momate®, to prevent secondary bacterial infections in patients sensitive to corticosteroid medicine
Table 3Changes in discharge from the lesions in the two groups
Example 1Momate®
Type detachableorigin (N=25) No.%day 6-7 (N=25) No.%day 13-14 (N=25)No.%origin (N=26) No.%day 6-7 (N=26), No.%day 13-14 (N=26), No.%
no-(-)*07 (28,0)16 (64,0) -(-)03 (11,5)06 (23,1)
serous04 (16,0)*10 (40,0)06 (24,0)05 (19,2)06 (23,1)09 (34,6)
purulent14 (56,0)05 (20,0)*02 (08,0)15 (57,7)12 (46,2)07 (26,9)
mucopurulent07 (28,0)03 (12,0)*01 (04,0)06 (23,1)05 (19,2)04 (15,4)
The Chi-square
*P<0,05 significant

In this group at the beginning of 80,8-84,0% of all studied cases were observed purulent or Muco-purulent type of discharge from the lesions. After treatment for 6-7 days in the group of Example 1 in 68,0% of the total number of cases was observed serous discharge or no discharge, which was significantly higher compared with 34.6% in the group Momate®. After treatment in the group of Example 1 12.0% of the t total number of cases was observed purulent or Muco-purulent type detachable, that was significantly lower compared to 42.3% in the group Momate®.

Bacteriological findings in this study showed that in both groups at the beginning of the countdown there was a significant growth of bacteria in 80,8-88,0% of the total number of cases. In both groups were allocated ordinary bacteria: Staphylococcus aureus, Streptococcus spp, after Epidermidis and Proteus spp. After treatment, patients treated according to Example 1 of the present invention, only 16.0% of cases there was a significant increase that was significantly lower compared to 57.5% in the group treated with the cream Momate®. When the overall assessment of the effectiveness of treatment by a physician in the group from Example 1 in 76,0% of the total number of cases was shown to be a complete cure or 90-99% cure rate by the sum of the signs and symptoms that were significantly higher compared to 23.1% in group Momate®. When the overall assessment of the effectiveness of treatment of patients in the group from Example 1 in 80,0% of the total number of cases have shown significant improvement, which was significantly higher compared to 23.1% in group Momate®.

The composition according to the present invention were evaluated for efficacy, safety and tolerability of the combined cream mometasone 0.1 wt.% and fusidic acid 2 wt.%, Example 1, in the treatment of patients with sensitive to corticosteroid dermatitis with secondary bacterial infections. A prospective, R is dominirovanie, single center, open study was conducted in one centre in 25 patients, male and female (post-menopausal age, undergone surgical sterilization, or use a reliable method of contraception) at the age from 12 to 65 years. The duration of the study was 3 weeks, including a 2-week period of active treatment, preceded by a 1-week washout phase. Performance parameters included changes in average scores on desquamation, erythema, itching/stinging, induration/swelling, pain, exudate/formation of crust, the amount of signs/symptoms, severity of lesions, discharge from the lesions, complete the overall evaluation of the effectiveness of therapist/patient, and monitoring the resulting over time of treatment side effects. Research data was gathered and analyzed the results using a nonparametric criterion. All criteria were bilateral, took a significance level of p<0,05.

In the group of the present study the average score for the amount of symptoms was 12,97 to the origin. After treatment for 6 to 7 days and the average score decreased significantly, i.e. by 42.5%. After 13-14 days fall in the average score amounted to 82.7 per cent from the start.

The results show that as the average scores for signs/symptoms, and total scores significantly reduce the knit together (p< 0,05) after the 1st week, and a significant decrease continued up to two weeks (p<0,05).

Table 5:
The results of changes in the severity of lesions for the combined cream mometasone 0.1 wt.% and fusidic acid 2 wt.% (Example 1 of the present invention) for treatment of patients sensitive to corticosteroid dermatitis with secondary bacterial infections
Table 5: results of changes in the severity of lesions
weightorigin (N=25)No.%day 6-7 (N=25)No.%day 13-14 (N=25)No.%
light04 16,0*07 28,0*20 80,0
moderate09 36,0*14 56,003 to 12.0
heavy12 48,004 16,002 08,0
The Chi-square
*P<0,05 significant

In Table 5 on Asano, that at the beginning of 52,0% of all cases in the study were observed lesions of mild or moderate severity. After treatment within 6-7 days of 84.0% of all cases there was mild or moderate severity of lesions, which represented a significant change, and the difference was significant. After treatment in 80.0% of cases were observed mild lesions, which has been a significant difference from the start.

Table 6:
Results changes in discharge from the lesions for combined cream mometasone 0.1 wt.% and fusidic acid 2 wt.% (example 1 of the present invention) for treatment of patients sensitive to corticosteroid dermatitis with secondary bacterial infections
Table 6: the effect of changing discharge from lesions
type detachableday 3 (N=25)No.%day 6-7 (N=25)No.%day 13-14 (N=25)No.%
no06 24,0*17 68,0
serous05 20,0 11 44,004 16,0
purulent14 56,0*06 24,003 to 12.0
mucopurulent06 24,0*02 08,001 04,0
The Chi-square
*P<0,05 significant

Table 6 shows that at the beginning of 80.0% of all cases in the study were observed discharge from the lesions purulent or Muco-purulent type. After treatment for 6 to 7 days only 32,0% of all cases observed the same type of discharge from the lesions that were statistically significantly different from the origin. After treatment in 68,0% of cases detachable were absent, and 16.0% of the observed serous discharge.

At the beginning of 88,0% of the total number of cases has been a significant growth of bacteria. Of them in 56,0% was detected Staphylococcus aureus, 20,0% Streptococcus spp, and 8.0% of Staphylococcus epidermidis. After treatment, the increase was only 8.0% of cases. There was a significant reduction (92%) of bacterial growth compared to the beginning point (P<0,05). According to estimates therapist in 32,0% of all cases in the study was observed in 100% remission of signs and symptoms, 44.0% of would is shown on the improvement of 90-99%, and in 20.0% of cases were shown a modest improvement. Estimated patients in 84,0% of all cases in the study showed a significant improvement, and 16,0% there was a slight improvement after treatment.

It is proved that the combined treatment cream mometasone furoate 0.1 wt.%, and fusidic acid 2 wt.%, Example 1 of the present invention, is effective in 100% of cases, and in 96% of cases there was a noticeable improvement or complete recovery of symptoms in the remaining 4% of cases, we also observed a modest improvement. We can conclude that the results obtained are superior to the results obtained Javier PR et al 1986 (Ref: Javier PR, Ortiz M, Torralba L, Montinola FL, ML Ke, R. Canete Fusidic acid/betamethasone in infected dermatoses--a double-blind comparison with neomycin/betamethasone. Br J Clin Pract. 1986; 40:235-8), for a combined cream betamethasone 0.1 percent plus fozilova acid 2%, where the efficiency was noticeable in 85% of cases. It is proved that a combination cream mometasone furoate 0.1 wt.% and fusidic acid 2 wt.%, Example 1 of the present invention is also effective for the destruction of bacterial organisms in 92% of cases. These results are detected as being superior to the results obtained Hjorth N, et al 1985 (Ref: Hjorth N, Schmidt H, Thomsen K.. Fusidic acid plus betamethasone in infected or potentially infected eczema. Pharmatherapeutica. 1985; 4:126-31.), where bacteriological cure was 67%, and Javier PR et al 1986, where bacteriological cure stood at the head amounted to 78%. The combined treatment cream mometasone furoate 0.1 wt.% and fusidic acid 2 wt.% according to the present invention provides a fast, best efficiency and safe portability.

The composition according to the present invention were evaluated for efficacy, safety and tolerability of the combined cream halobetasol propionate of 0.05 wt.% and fusidic acid 2 wt.%, Example 4 in comparison with the cream of halobetasol propionate of 0.05 wt.% Halbate®sold by Glenmark Pharmaceutical Ltd. in India, to prevent secondary bacterial infections in patients with non-infected dermatoses.

A prospective, randomized, multicenter, open study was performed on 25 patients, male and female (post-menopausal age, undergone surgical sterilization, or use a reliable method of contraception) at the age from 12 to 65 years. The duration of the study was 3 weeks, including a 2-week period of active treatment, preceded by a 1-week washout phase. The selected patients were clinically diagnosed non-infected dermatoses. Exclusion criteria patients were pregnancy and lactation, serious skin diseases, pigmentation disorders and extensive scarring in the affected areas, hypersensitivity to halobetasol Il is clobetasol or salicylic acid or base ointment, state of impaired immunity, patients with common infections, patients who participated in studies of new drugs in the last 6 months, patients with severe heart disease, liver, kidney or brain vessels, a malignant tumor, chronic uncontrolled systemic diseases, such as diabetes, hypertension, asthma, collagen, etc. or other serious medical conditions.

Plan research
Action/observationScreeningVisit IVisit IIVisit III
visit (Day 7)(origin/Day 0)(Day 6-7)(Day 13-14)
Demographic dataX
The patient's history and medical examinationX
Cree is ' series include/exclude X
Informed consentX
ClinicalXXXX
score
Laboratory and other studiesX
The introduction of an investigational medicationXXX
Side effectsXXX
The compliance of patients treatmentXX
General assessment of effectivenessXX
Bacteriological examinationXX

Screening visit:

Recorded demographic data and medical history of the patients, and conducted a brief medical examination. Patients were recruited on the basis of the criteria of inclusion and exclusion. Received written informed consent from selected patients. During this visit conducted clinical assessment before the examination, laboratory studies, chest x-ray and ECG. Patients underwent a 1-week washout period, after which he began the study treatment.

The estimated parameters of clinical effectiveness:

The present study was designed to observe clinical signs and symptoms such as peeling, erythema, pruritus, induration/swelling, pain, exudation/scum formation, and the amount of signs/symptoms. Additionally watched the severity of the lesions, discharge from the lesions, the results of bacteriological tests and the results of bacteriological tests in the including Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus spp Enterobacteriaceae.

Investigational treatment

Patients received combined cream halobetasol propionate of 0.05 wt.% and fusidic acid 2 wt.% or cream halobetasol propionate of 0.05 wt.% in accordance with a random distribution by applying onto the affected area twice a day in a thin layer, with careful and complete rubbing, and each application separated by intervals of about 12 hours.

Full General assessment of effectiveness

At the end of the study performed a full evaluation of the effectiveness of the drug as a researcher and patient.

The overall score therapist included the following parameters:

ScoreScore
1complete recovery (100% remission of signs and symptoms)
2excellent (90-99% improvement)
3good (75-89% improvement)
4moderate (50-74% improvement)
5weak (30-49% improvement)
6no improvement (0-29%)
7worse than (<0%)
General assessment of the patient
ScoreScore
1much better
2somewhat better
3as well
4worse
5much worse

The compliance of patients to treatment was assessed at visits II, III and IV by direct questioning of the patients.

The results of the study:

Collected research data to assess the effectiveness of the combined cream halobetasol propionate of 0.05 wt.% and fusidic acid 2 wt.%, Example 4 of the present invention, compared with the cream of halobetasol propionate of 0.05 wt.%, Halbate®to prevent secondary bacterial infections in patients with non-infected dermatoses, and analyzed the resulting data using nonparametric criterion. All criteria were bilateral, took a significance level of p<0,05.

Table 1A shows that, after treatment, the average score peeling with the single patients, receiving a combined cream halobetasol and fusidic acid, Example 4, was 80.5%, which was significantly higher compared with 60.3% of the patients treated with the cream of halobetasol, Halbate®. After treatment, the average score for erythema in patients receiving combined cream halobetasol and fusidic acid, Example 4, dropped to 83.5%, which was significantly higher compared with 60.8% of patients treated cream halobetasol, Halbate®. After treatment, the average score of itching in patients receiving combined cream halobetasol and fusidic acid, Example 4, decreased by $ 78.2%, which was significantly higher compared with 53.4% in patients treated with the cream of halobetasol, Halbate®. After treatment, the average score of the seal/edema in patients receiving combined cream halobetasol and fusidic acid, Example 4, decreased $ 82.9%, which was significantly higher compared with 46.2% of patients treated cream halobetasol, Halbate®. After treatment, the average score for pain in patients receiving combined cream halobetasol and fusidic acid, Example 4, decreased 80.1%, which was significantly higher compared to 57.2% in patients treated cream halobetasol. After treatment, the average score for exudation in patients receiving combined cream halobetasol and fusidic acid, the example 4, decreased by 73.2 per cent, which was significantly higher compared to 55.6% of patients treated cream halobetasol, Halbate®. After treatment, the average score by the sum of the signs and symptoms in patients receiving combined cream halobetasol and fusidic acid, Example 4, decreased by 80.9 per cent, which was significantly higher compared to 55.9% in patients treated with the cream of halobetasol, Halbate®.

Table 2A:
The results of changes in the severity of lesions for combined cream halobetasol and fusidic acid (Example 4 of the present invention) compared with cream halobetasol propionate of 0.05 wt.%, Halbate®to prevent secondary bacterial infections in patients with non-infected dermatoses
Table 2AChanges in severity of lesions between the two groups
Example 4Halbate®
weightorigin (N=28) No.%day 6-7 (N=28) No.%day 13-14 (N=28), No.%origin (N=27), No.%day 13-14 (N=27) No.%
light04 (14,2)08 (28,6)*22(78,7)05 (18,6)06 (22,2)10 (37,0)
moderate12 (42,9)13 (46,4)04 (14,2)11 (40.7 in)12 (44,5)11 (40,8)
heavy12 (42,9)07 (25,0)02 (07,1)11 (40.7 in)09 (33,3)06 (22,2)

At the end of treatment in patients receiving combined cream halobetasol and fusidic acid, Example 4 of the present invention, to 78.7% of the total number of cases was observed lesions of mild severity, which was significantly higher compared to 37,0% in patients treated with the cream of halobetasol, Halbate®.

Table 3A:
Results changes in discharge from the lesions for combined cream globe is Azola and fusidic acid (Example 4 of the present invention) compared with cream halobetasol propionate of 0.05 wt.%, Halbate®to prevent secondary bacterial infections in patients with non-infected dermatoses
Table 3AChanges in discharge from the lesions in the two groups
Example 4Halbate®
Type detachableorigin (N=28) No.%day 6-7 (N=28) No.%day 13-14 (N=28), No.%origin (N=27) No.%day 6-7 (N=27) No.%day 13-14 (N=27), No.%
no23 (82,2)24 (85,7)*22 (78,5)23 (to 85.2)13 (48,2)*06 (22,2)
serous05 (17,8)04 (14,3)04 (14,3)04 (14,8)06 (22,2)10 (37,0)
purulent00 (00)00 (00)*01 (03,6)6 (22,2)*08 (29,7)
mucopurulent00 (00)00 (00)01 (03,6)00 (00)02 (7,4)03 (11,1)
The Chi-square
*P<0,05 significant

The results show that patients treated with combined cream halobetasol propionate of 0.05 wt.%, and fusidic acid 2 wt.%, Example 4 in comparison with patients treated with the cream of halobetasol propionate 0.05%, the Halbate®there was a significant decrease (p<0,05) as average scores on symptoms/signs, and overall scores after 1 week, and significantly lasted for two weeks (p<0,05). In both groups at the beginning of the countdown was not observed discharge purulent or Muco-purulent type. After treatment of purulent or Muco-purulent discharge in patients receiving combined cream halobetasol propionate of 0.05 wt.% and fusidic acid 2 wt.% was observed in 7.2% of the total number of cases, which was significantly lower compared to 40.8% of patients treated with the cream of halobetasol propionate 0.05%, the Halbate®(p<0.05). In both g is uppah at the beginning of 89,2-92,5% of the total number of cases has been a significant growth of bacteria, and between groups there was no significant difference. Normal selected bacteria in both groups were Staphylococcus aureus. At the end of treatment in patients receiving combined cream halobetasol propionate of 0.05 wt.% and fusidic acid 2 wt.%, Example 4, only 7.2% of the total number of cases there was a significant increase that was significantly much lower compared to 55.6% of patients treated Halbate®(p<0,05). When the overall assessment of the effectiveness of treatment by a physician in patients receiving combined cream halobetasol propionate of 0.05 wt.% and fusidic acid 2 wt.%, Example 4, in 78.6% of the total number of cases there was a complete cure by the sum of the signs and symptoms that were significantly higher compared with 26.0% of patients receiving Halbate®(p<0,05). When the overall assessment of the effectiveness of treatment of patients in the group of patients treated with combined cream halobetasol propionate of 0.05 wt.% and fusidic acid 2 wt.%, Example 4, in 78.6% of the total number of cases showed significant improvement, which was significantly higher compared with 25.9% in the group treated Halbate®(p<0,05).

The composition according to the present invention were evaluated for efficacy, safety and tolerability of the combined cream halobetasol of 0.05 wt.% and fusidic acid 2 wt.%, Example 4, in the treatment of patients infected with the medicine is. A prospective, randomized, single center, open study was conducted in one centre in 25 patients, male and female (post-menopausal age, undergone surgical sterilization, or use a reliable method of contraception) at the age from 12 to 65 years, with clinically diagnosed infected dermatoses with secondary bacterial infections, confirmed by laboratory evaluation (staining Gram and seeding). Patients who meet the selection criteria after you receive the informed consent, were prescribed treatment with combined cream halobetasol propionate of 0.05 wt.% and fusidic acid 2 wt.%, Example 4 local daily every 12 hours for 2 weeks. The duration of the study was 3 weeks, including a 2-week period of active treatment, preceded by a 1-week washout phase. Performance parameters included changes in average scores on desquamation, erythema, itching/stinging, induration/swelling, pain, exudate/formation of crust, total score of the signs/symptoms, severity of lesions, discharge from the lesions, complete the overall evaluation of the effectiveness of therapist/patient, and monitoring the resulting over time of treatment side effects. Research data was gathered and analyzed the results using nonparametric critter who I am. All criteria were bilateral, took a significance level of p<0,05.

Table 4A:
The results of the evaluation of clinical symptoms for a combined cream halobetasol propionate of 0.05 wt.% and fusidic acid 2 wt.%, Example 4, in the treatment of patients with infected dermatoses
Table 4AThe average total score
ReadingsThe effect on the peelingEffect on erythemaEffect on itching
Duration in daysExample 4% changeExample 4% changeExample 4% change
origin2,39±0,692,44±0,792,30±0,90
6-729,3*1,19±0,7051,2*1,22±0,6446,9
13-14*0,33±0,4886,2*0,28±0,5088,5*0,49±0,5378,7
ReadingsThe effect on the seal/swellingEffect on painEffect on exudation
Duration in daysExample 4% changeExample 4% changeExample 4% change
origin2,13±0,752,33±0,831,61±0,74
6-7*1,12±0,6647,41,21±0,6748,1 *0,85±0,49to 47.2
13-14*0,51±0,5976,1*0,42±0,6081,9*0,36±0,4877,6
On sign-rank criterion of Wilcoxon signed
*P<0,05) from baseline significant

In the present study the average score for the amount of symptoms was 13,20 to the origin. After treatment for 6 to 7 days shows a significant reduction in the average score, i.e. 44,8%. After 13-14 days fall in the average score amounted to 81.9% from the start.

Table 5A:
The results of changes in the severity of lesions for combined cream halobetasol propionate of 0.05 wt.% and fusidic acid 2 wt.%, Example 4, in the treatment of patients with infected dermatoses
Table 5A: results of changes in the severity of lesions
WeightOrigin (N=28), No.%Day 6-7 (N=28), No.%Day 13-14 (N=28), No.%
light05 17,9*09 32,1*23 82,1
moderate10 35,7*46,5 1303 10,8
heavy13 46,406 21,402 07,1
The Chi-square
*P<0,05 significant

Table 5A shows that at the beginning of 53,6% of all cases in the study were observed lesions from mild to moderate severity. After treatment for 6-7 days in 78,6% of all cases there was mild or moderate severity of lesions, which represented a significant change, and the difference was significant. After treatment in 82.1% of the cases were observed mild lesions, which has been a significant difference from the start.

Table 6A:
Results changes in discharge from the lesions for combined cream halobetasol propionate of 0.05 wt.% and fusidic acid 2 wt.%, Example 4, in the treatment of patients with infected dermatoses
Table 6A: results of changing discharge from lesions
Type detachableday 3 (N=28), No. %day 6-7 (N=28), No.%day 13-14 (N=28), No.%
no07 25,0*19 67,9
serous06 21,411 39,305 17,9
purulent15 53,6*07 25,002 07,1
mucopurulent07 25,0*03 10,702 07,1
The Chi-square
*P<0,05 significant

Table 6A shows that at the beginning of 78,6% of all cases in the study were observed discharge from the lesions purulent or Muco-purulent type. After treatment for 6 to 7 days only 35.7% of all cases observed the same type of discharge from the lesions that were statistically significantly different from the origin. After treatment after treatment according to Example 4 in 67.9% of cases the Department is jaimoe was absent, and 17.9% were observed serous discharge.

The results showed that in the case of combined treatment cream halobetasol propionate of 0.05 wt.% and fusidic acid 2 wt.%, Example 4, there was a significant decrease (p<0,05) as average scores on signs/symptoms, and total scores after 1 week, and significantly lasted for two weeks (p<0.05) in the treatment of patients with infected dermatoses. At the beginning of 82.1 per cent of the total number of cases has been a significant growth of bacteria. Of them at 46.4% detected Staphylococcus aureus, 1.4% Streptococcus spp and 7.1% of Proteus spp. After treatment, the growth was only observed in 10.7% of cases, which is considerably lower than at the beginning of the countdown. There was a significant decrease (89.3 per cent) of bacterial growth compared to the beginning point (P<0,05). It is proved that a combination cream halobetasol propionate of 0.05 wt.% and fusidic acid 2 wt.% according to the present invention was effective in 100% of cases, with 92.9% of the cases shown marked improvement or complete recovery of symptoms, and the remaining 7.1% of cases are also shown modest improvement. Only 6.7% of the total number of cases observed side effects. Of them in each individual case there was a burning sensation, irritation, and dryness of the skin. In both cases, which disappeared in the course of treatment, was observed mild or reasonable price which I severity of side effects. It is proved that a combination cream halobetasol propionate of 0.05 wt.% and fusidic acid 2 wt.% according to the present invention was effective in 100% of cases, with 92.9% of the cases shown marked improvement or complete recovery of symptoms, and the remaining 7.1% of cases are also shown modest improvement.

The results obtained are superior to the results obtained Javier PR et al 1986 (Ref: Javier PR, Ortiz M, Torralba L, Montinola FL, ML Ke, R. Canete Fusidic acid/betamethasone in infected dermatoses-a double-blind comparison with neomycin/betamethasone. Br J Clin Pract. 1986; 40:235-8), with a fixed dose combination of cream betamethasone 0.1 wt.% and fusidic acid 2 wt.%, where effectiveness was evident in 85% of cases. In the study of halobetasol propionate of 0.05 wt.% Kantor et al 1991 (Ref: Kantor I, Cook PR, Cullen SI, et al. Double-blind bilateral paired comparison of 0.05% halobetasol propionate cream and its vehicle in patients with chronic atopic dermatitis and other eczematous dermatoses. J Am Acad Dermatol 1991 Dec; 25 (6 Pt2): 1184-6), in patients with atopic dermatitis and other eczematous dermatoses, shows excellent or good clinical improvement in 87% of cases. It has also been proven that a combination cream halobetasol propionate of 0.05 wt.% and fusidic acid 2 wt.% according to the present invention effectively eliminates bacterial organisms in 89,3% of cases. Found that the results obtained are superior to the results obtained Hjorth N, et al 1985 (Ref: Hjorth N, Schmidt H, Thomsen K.. Fusidic acid plus betamethasone in infected or potentially infected ezema. Pharmatherapeutica. 1985; 4:126-31), where bacteriological cure was 67% and Javier PR et al 1986, where bacteriological cure was 78%.

Therapy combined cream halobetasol propionate of 0.05 wt.%, and fusidic acid 2 wt.% according to the present invention provides a fast, best efficiency and safe portability.

It should be understood that in the embodiments, described herein, can be made different changes. Therefore, the above description should not be construed as limiting, but merely as illustrations of the preferred options for implementation. For example, the functions described above and implemented as the best course of action according to the present invention, is shown for illustrative purposes only. The person skilled in the art can use other layout and ways without going beyond the scope and essence of the present invention.

1. Pharmaceutical composition for topical application containing guideway acid in the range from 1 wt.% up to 5 wt.% and mometasone furoate in the range from 0.05 wt.% up to 2 wt.% and pharmaceutically acceptable carrier for use in the treatment or prevention of inflammatory dermatosis associated with secondary bacterial infection in a patient.

2. Pharmaceutical composition for topical application at p., characterized in that the said composition comprises 2 wt.% fusidic acid, 0.1 wt.% mometasone furoate, with the specified dermatosis is a infected eczema.

3. Pharmaceutical composition for topical application according to claim 1, characterized in that the mass ratio of mometasone furoate to fusidic acid is in the range from 1:2.5 to 1:20.

4. Pharmaceutical composition for topical application according to claim 1, characterized in that the mass ratio of mometasone furoate to fusidic acid is in the range from 1:10 to 1:20.

5. Pharmaceutical composition for topical application containing guideway acid in the range from 1 wt.% up to 5 wt.% and halobetasol propionate in the range from 0.01 wt.% up to 2 wt.% and pharmaceutically acceptable carrier for use in the treatment or prevention of inflammatory dermatosis associated with secondary bacterial infection in a patient.

6. Pharmaceutical composition for topical application according to claim 5, characterized in that the said composition comprises 2 wt.% fusidic acid is 0.05 wt.% halobetasol propionate, and the specified composition is used to prevent secondary bacterial infection in uninfected skin and/or treating sensitive to steroids infected dermatosis in a patient.

7. Pharmaceutical HDMI is required for local use according to claim 5, characterized in that the mass ratio of halobetasol propionate to fusidic acid is in the range from 1:2.5 to 1:100.

8. Pharmaceutical composition for topical application according to claim 7, characterized in that the mass ratio of halobetasol propionate to fusidic acid is in the range from 1:30 to 1:50.

9. A method of treating or preventing an infected eczema, including secondarily infected dermatitis, allergic contact dermatitis, atopic dermatitis and psoriasis, the patient, and the method includes the local application of the indicated patient a pharmaceutical composition according to any one of claims 1 to 4.

10. The way to prevent a secondary bacterial infection in patients with uninfected skin, and this method includes the local application of the indicated patient a pharmaceutical composition according to any one of pp.5-8.

11. A method of treating sensitive to steroids infected dermatosis, including secondarily infected contact dermatitis, allergic contact dermatitis, atopic dermatitis and psoriasis, the patient, and the method includes the local application of the indicated patient a pharmaceutical composition according to any one of pp.5-8.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds of formula (I) and its pharmaceutically acceptable salts possessing dihydroorotate dehydrogenase inhibitory ability, to a based pharmaceutical composition, to application thereof in preparing a drug compound and to a combined preparation containing the presented compounds and the other active compound (I) in effective amounts wherein both groups G1 mean CRC, G2 mean a nitrogen atom or group CRd, of the groups G3 and G4 mean a nitrogen atom and the other one means group CH, M means a hydrogen atom or a pharmaceutically acceptable cation, while R1, R2, Ra, Rb, Rc and Rd have the values specified in the patent claim.

EFFECT: preparing pharmaceutically acceptable salts possessing dihydroorotate dehydrogenase inhibitory ability.

25 cl, 115 ex, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to method of obtaining said salts, to pharmaceutical composition, containing said salts, and to application of salt for preparation of medication for treatment, prevention or relief of one or several symptoms of disease, mediated by CRTH2, associated with eosinophils, basophils, where disease is selected from asthma, allergic asthma, asthma of physical effort, allergic rhinitis, atopic dermatitis, contact hypersensitivity and hyper IgE syndrome.

EFFECT: invention relates to novel pharmaceutically acceptable salts, containing pharmaceutically acceptable amine, selected from ethylenediamine, piperazine, benzathine or choline and {4,6-bis(dimethylamino)-2-(4-(4-(trifluoromethyl)benzamido)benzyl)pyrimidin-5yl}acetic acid.

43 cl, 21 dwg, 4 tbl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel crystalline forms I, II and amorphous form of {4,6-bis(dimethylamino)-2-(4-(4-(trifluoromethyl)benzamido)benzyl)pyrimidin-5-yl}acetic acid.

EFFECT: invention relates to pharmaceutical composition, containing crystalline form I of compound and to application of crystalline form I for treatment, prevention or relief of one or more symptoms of disease, mediated by CRTH2, associated with eosinophils, basophils, where disease is selected from asthma, allergic asthma, asthma, induced by physical effort, allergic rhinitis, perennial allergic rhinitis, seasonal allergic rhinitis, atopic dermatitis, contact hypersensitivity.

16 cl, 11 dwg, 8 tbl,11 ex

FIELD: medicine.

SUBSTANCE: what is described is a composition for topical application which contains a continuous phase and at least one disperse phase with said composition containing at least one polyaphron dispersion, at least one vitamin D or vitamin D analogue.

EFFECT: composition is characterised by better skin penetration or better stability.

27 cl, 3 dwg, 17 ex

FIELD: medicine.

SUBSTANCE: method of treating psoriasis. The invention refers to medicine, specifically to dermatology, and may be used for treating the patients suffering psoriasis. That is ensured by conducting detoxification, hyposensitising therapy, prescribing antihistamine preparations, vitamins, cytostatics, physiotherapeutic therapy, ointment applications. The conducted therapy is combined with additionally prescribed oral 40% alcoholate (1:10) containing herbal phytoecdysteroids in mass fractions 50 drops 3 times a day 15 minutes before meal daily for 30 days: Rhaponticum carthamoides roots and rhinzomes - 3, pot marigold blossom - 1, wild camomile blossom - 1.

EFFECT: method enabled considerably improved therapeutic effect in the patients due to evident immunomodulating, adaptogenic, sedative and anti-inflammatory effects of herbal phytoecdysteroids.

2 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to dermatology and can be applied for external treatment of psoriatic onychodystrophy. For this purpose mixture of gel tisol and ointment daivonex is applied on nidus of affection in ratio 1:2 with following keeping under adhesive plaster during 8-10 h two times per day. Course of treatment constitutes not less than 14 days.

EFFECT: method ensures reduction of treatment terms and duration of remission and obtaining high therapeutic effect.

1 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to chemical-pharmaceutical industry, and concerns preparing an agent for treating various dermatopathies: psoriasis, eczema, atopic dermatitis, ulcers incl. trophic and other diseases accompanied by inflammation or skin flaking. According to the first version, the composition contains ethoxylated alcohol, glycerol monostearate, higher fatty alcohols C16-C18 and cocoglycerides, as well as glycerol, olive oil and water. According to the other versions, it contains naphthalan oil or pentoxifylline or urea. All the versions provide a liposomal form of the composition improving healing, soothing and trophic effects.

EFFECT: composition is hypoallergic, easy-to-use.

12 cl, 8 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new benzimidazole derivatives of general formula (I) or to its pharmacologically acceptable salts wherein R1 represents a C6-aryl group which can be substituted by 1-3 groups optionally specified in a group of substitutes (a), or a heterocyclic group which represents pyridyl, dihydrobenzofuranyl, 1,3-benzodioxolyl, tetrahydropyranyl, tetrahydrofuranyl which can be substituted by 1-3 groups optionally specified in a group of substitutes (a), R2 represents a C1-C6 alkyl group, R3 represents a C6-aryl group which can be substituted by 1-2 groups optionally specified in a group of substitutes (a), Q represents a group represented by formula =CH-, or a nitrogen atom and a group of substitutes (a) represents a group consisting of a halogen atom, a C1-C6 alkyl group, a C1-C6 halogenated alkyl group, a carboxyl group, a C2-C7 alkylcarbonyl group, a C2-C7 alkoxycarbonyl group, a C1-C6 alkoxy group, a C1-C6 halogenated alkoxy group, an amino group, a 4-morpholinyl group and a di-C1-C6 alkyl)amino group. Also, the invention refers to a pharmaceutical composition based on a compound of formula (I), to a PPARγ activator/modulator based on the compound of formula (I), to using the compound of formula (I), to a method of reducing blood glucose, to a method of activating PPARγ, a method of treating and/or preventing said pathological conditions.

EFFECT: there are produced new benzimidazole derivatives showing PPARγ modulatory activity.

41 cl, 2 dwg, 6 tbl, 76 ex

FIELD: chemistry.

SUBSTANCE: invention describes a novel useful vitamin D3 derivative, which has excellent vitamin D3 activity, and has relatively low action on system calcium metabolism compared to other traditional vitamin D3 derivatives. The invention includes a 9,10-secopregnane derivative of general formula [1] and a pharmaceutical composition containing said derivative as an active ingredient. [Formula 1]

.

In general formula [1], the next part of the structure between position 16 and position 17 denotes a single bond or a double bond. Y denotes a single bond, alkylene, alkenylene or phenylene; R1 and R2 are identical or different and each denotes hydrogen, alkyl or cycloalkyl; or R1 and R2, taken together with an adjacent carbon atom, form a cycloalkyl; R3 denotes hydrogen or methyl; Z denotes hydrogen, hydroxy or -NR11R12, where R11 and R12 assume values given in the claim.

EFFECT: obtaining a useful D3 derivative.

14 cl, 73 ex, 8 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel diarylamine-containing compounds of formula (I) or formula (4b), pharmaceutically acceptable salts thereof, which have c-kit inhibiting properties. In formulae (I) and (4b), each R1 independently denotes H, -C(O)OH and -L1-C1-6alkyl, where L1 denotes -O- or -C(O)O-, or any two neighbouring R1 groups can together form a 5-6-member heterocyclic ring containing a nitrogen atom or an oxygen atom as a heteroatom, a 6-member heterocyclic ring with one or two nitrogen atom s as heteroatoms, optionally substituted with a C1-4alkyl, and R5 denotes hydrogen or C1-C6alkyl; values of radicals Ar and Q are given in the claim. The invention also relates to a pharmaceutical composition containing said compounds, and a method of treating diseases whose development is promoted by c-kit receptor activity.

EFFECT: more effective use of the compounds.

17 cl, 3 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmacology and represents a drug preparation for treating respiratory diseases for simultaneous, sequential or separate inhalation introduction containing crystalline monteleukast in the form of an acid and mometasone.

EFFECT: invention provides extended range of the combined drug preparations for treating respiratory diseases in the form of inhalation.

7 cl, 5 ex, 17 tbl, 1 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel estratrien-triazoles of general formula (I), which are useful in therapy, especially in treating and/or preventing steroid hormone dependent disorders, preferably steroid hormone dependent diseases or disorders requiring the inhibition of 17β-hydroxysteroid dehydrogenase (17β-HSD) such as 17β-HSD type 1, type 2 or type 3 enzyme.

EFFECT: improved method.

21 cl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to homogenous pharmaceutical composition for treatment of inflammatory disorders, which contains mixture of steroid anti-inflammatory or anti-histamine active ingredient in pharmaceutically acceptable water carrier with liposome. As steroid anti-inflammatory ingredient used is budesonide or fluticasone or their pharmaceutically acceptable salt, and antihistamine preparation is represented by azelastine or its pharmaceutically acceptable salt, concentration of active ingredient in water carrier is, in fact, equal inside and outside liposomic structures and varies ±20% when concentration of active ingredient inside and outside liposomic structures is compared. Polar lipid is swellable in water and represents phospholipid or glycosphingolipid. Invention also relates to method of composition obtaining, which lies in joint mixing of polar lipid, water phase and said active ingredient and mixture homogenising. Invention also relates to method of treating inflammatory disorders, including introduction of claimed composition to individuum, suffering from or sensitive to said disorders.

EFFECT: invention ensures reduction of irritation, for instance, in case of nasal introduction of composition.

52 cl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention describes compounds applicable for treating or relieving a neurodegenerative disorder. There are also described methods of treating or relieving said disorders with said method involving the introduction a compound according to the present invention or a composition containing said compound in a patient.

EFFECT: method may be applicable for treating or relieving eg Alzheimer's disease.

21 cl, 9 ex, 22 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to substituted extratriene derivatives of general formula (values of radicals are given in the claim), useful in therapy, especially for treating and/or preventing steroid hormone-dependent disorders which require inhibition of 17β-hydroxysteroid dehydrogenase (17-HSD) enzyme type 1, type 2 and/or type 3, as well as salts thereof, pharmaceutical preparations containing said compounds, as well as methods of producing said compounds.

EFFECT: improved method.

41 cl, 98 ex

FIELD: medicine.

SUBSTANCE: invention refers to pharmaceutical industry, particularly a composition for preventing or treating peripheral neuropathy. The pharmaceutical composition for preventing or treating peripheral neuropathy containing a therapeutically effective amount of a compound presented by formula 1, or its salt and a pharmaceutically acceptable carrier: [Formula 1]

wherein R is a hydrogen atom, alkyl group C1-C4 or saccharide. A food composition for preventing or treating peripheral neuropathy containing the compound presented by formula 1, or its salt as an active ingredient.

EFFECT: compositions described above for preventing or treating peripheral neuropathy.

6 cl, 9 dwg, 1 tbl, 15 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: as a first active agent a pharmaceutical composition contains drospirenone in the amount equal to a daily dose when administering the composition and making 2 to 4 mg, and as a second active agent - ethinylestradiol in the amount equal to a daily dose and making 0.01 mg to 0.05 mg, together with one or more pharmaceutically acceptable carriers or additives. Drospirenone as a part of the pharmaceutical composition has a particle surface area more than 10000 cm2/g. Preferentially, drospirenone is fine-grained or sprayed from a drospirenone solution by inert carrier particles. The preparation contains a number of separately packed and individually taken daily dosage units in a single package used for oral administration for at least 21 days running with said daily dosage units containing a combination of drospirenone and ethinylestradiol. The preparation may additionally contain 7 and less daily dosage units containing no active agent, or containing ethinylestradiol only.

EFFECT: combination of drospirenone and ethinylestradiol provides reliable contraceptive activity ensured by the use of a maximum dose of drospirenone which causes no side effects, particularly, excess diuresis.

29 cl, 5 dwg

FIELD: medicine.

SUBSTANCE: invention also describes methods of treatment or reduction of such malfunctions severity, including introduction into patient's organism of compound according to claimed invention or composition, which contains it.

EFFECT: method is useful for treatment or reduction of difficulty, for example, Alzheimer's disease.

20 cl, 2 ex, 22 dwg

FIELD: chemistry.

SUBSTANCE: invention describes novel 18-methyl-19-norandrost-4-ene 17,17-spiroethers of general formula 1 in which Z denotes an oxygen atom, R4 denotes a hydrogen atom, a chlorine atom, R6 and/or R7 can have an α or β configuration, and R6 and R7 independently denote a hydrogen atom or straight or branched alkyl group containing 1-4 or 3-4 carbon atoms, or a straight or branched alkenyl group containing 2-4 or 3-4 carbon atoms, or a saturated cycloalkyl group containing 3-5 carbon atoms, or together denote a methylene group or a double bond.

EFFECT: novel compounds have progestational activity and antimineralocorticoid activity.

2 cl, 20 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to neonatology, and can be used for prevention of development of severe forms of bronchopulmonary dysplasia (BPD) in preterm newborn babies. For this purpose, in child of 3-4 days old presence of at least two of five criteria is detected: 1) gestation age <32 weeks, 2) performing artificial lung ventilation (ALV) for not less than 3 days or application of respiratory support with positive pressure in respiratory ways through nasal catheters, 3) dependence on oxygen in concentration more than 21% for not less than 3 days, 4) presence of symptoms of respiratory failure (RF) for more than 3 days, 5) X-ray changes in form of interstitial edema, nodose-reticular network, increased pneumatisation, homogenous shadows without hyperinflation. In case if at least two of said criteria are present, nebuliser treatment with budesonide is administered; if child had symptoms of moderate severe or severe RF, simultaneously inhalations with berodual or atrovent are carried out; in case of impossibility to disconnect child from ALV apparatus, aminofylline is added. On the 14-th day of life repeated examination is performed. From 14 to 28 day of life inhalations with budesonide are continued, in case of RF is absent; in case of RF of I-III degree - inhalations with budesonide with addition of berodual or atrovent, in case of impossibility to disconnect child from ALV apparatus, dexamethasone is applied.

EFFECT: invention contributes to efficient prevention of development of severe BPD in children of risk group due to differentiated administration of drug therapy.

1 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine and concerns a pharmaceutical composition containing cholest-4-en-3-one oxime and oil specified in sesame oil, olive oil, soya oil, cottonseed oil or mixed medium-chain triglycerides (ESTASAN®, MYGLIOL®) or mixed oils, preferentially sesame oil, olive oil and soya oil, more preferentially sesame oil.

EFFECT: invention ensures chemical stability of the dosage form, higher concentration of the solubilised active ingredients, higher biological availability of the active ingredient.

6 cl, 4 ex

Up!