TR201613662A1 - PHARMACEUTICAL FORMULATIONS - Google Patents

Abstract

The present invention includes; primary and secondary adrenal insufficiency, acute adrenocortical insufficiency, congenital adrenal hyperplasia, cancer-associated hypercalcemia, nonsupurative thyroiditis, rheumatoid arthritis, psoriatic arthritis (including juvenile rheumatoid arthritis), ankylosing spondylitis, acute gout arthritis, post-traumatic non-osteovritos , acute / subacute bursitis and epicondylitis, systemic lupus erythematosus, systemic dermatomyositis and acute rheumatoid carditis, pemphigus, erythema multiform (Stevens-Johnson syndrome) exfoliative dermatitis, bull dermatitis herpetiformis, severe psoriasis, seborrheic dermatitis and mycosis fungoides, herpes zoster iritis, iridocyclitis chorioretinitis, diffuse posterior uveitis and choroiditis, optic neuritis, sympathetic ophthalmia, anterior segment inflammation, allergic conjunctivitis, allergic corneal marginal ulcer and keratitis, bronchial asthma, contact dermatitis, atopic dermatitis, serum disease, seasonal or long-term allergic rhinitis. , excessive drug sensitivity, rtikeriyel transfusion reactions and acute non-infectious laryngeal edema, symptomatic sarcoidosis, berilliosis, untreatable Löffler's syndrome, aspiration pneumonitis and required anti-fulminant with treatment of tuberculosis or disseminated pulmonary tuberculosis, acquired (autoimmune) hemolytic anemia, secondary thrombocytopenia in adults, erythroblastopenia and monotherapy of the appropriate anti-inflammatory and immunosuppressive glucocorticoid group for use in the symptomatic and / or prophylactic and / or therapeutic treatment of congenital hypoplastic anemia, multiple sclerosis, ulcerative colitis and regional enteritis; and / or the pharmaceutical composition (s) wherein this active ingredient is used as a combined treatment with other suitable active agent (s).

Description

DESCRIPTION PHARMACEUTICAL FORMULATIONS The present invention; primary and secondary adrenal insufficiency, acute adrenocortical insufficiency, congenital adrenal hyperplasia, cancer-related hypercalcemia, nonsuppurative thyroiditis, rheumatoid arthritis, psoriatic arthritis (including juvenile rheumatoid arthritis), ankylosing spondylitis, acute gouty arthritis, post-traumatic osteoarthritis, acute non-specific tendosynovitis, acute/subacute bursitis and epicondylitis, systemic lupus erythematosus, systemic dermatomyositis and acute rheumatoid carditis, pemphigus, erythema multiforme (Stevens-Johnson syndrome) exfoliative dermatitis, bullous dermatitis herpetiformis, severe psoriasis, seborrheic dermatitis and mycosis fungoides, herpes zoster ophthalmicus, iritis, iridocyclitis chorioretinitis, diffuse posterior uveitis and choroiditis, optic neuritis, sympathetic ophthalmia, anterior segment inflammation, allergic conjunctivitis, allergic corneal marginal ulcer and keratitis, bronchial asthma, contact dermatitis, atopic dermatitis, serum sickness, seasonal or perennial allergic rhinitis, drug hypersensitivity, urticarial transition reactions and acute non-infectious laryngeal edema, symptomatic sarcoidosis, berylliosis, incurable Löffler syndrome, aspiration pneumonia and necessary anti- Fulminated or disseminated pulmonary tuberculosis with tuberculosis therapy, acquired (autoimmune) hemolytic anemia, secondary thrombocytopenia in adults, erythroblastopenia, congenital hypoplastic anemia, multiple sclerosis, ulcerative colitis and regional enteritis for use in the symptomatic and/or prophylactic and/or therapeutic treatment Suitable for glucocorticoids with anti-inflammatory and immunosuppressive properties active ingredient and/or pharmaceutically acceptable derivatives as monotherapy alone used alone and/or in combination with other suitable active agent/s relates to the pharmaceutical composition(s) for which it is used as a treatment.

The present invention is in the glucocorticoid group with anti-inflammatory and immunosuppressive properties. taking Prednisolone (11ß)-11,17,21-Trihydroxypregna-1,4-diene-3,20-dione (Formula 1) and/or alone as monotherapy, for which there are pharmaceutically acceptable derivatives used and/or as a combined treatment of this active substance with other suitable agent/s relates to the pharmaceutical composition(s) for which it is used.

Formula I: In addition, the invention includes the use of Prednisolone and/or its pharmaceutically acceptable derivatives. It is used alone as monotherapy or when this active substance is combined with other suitable agent/s. Oral and/or parenteral administration of pharmaceutical composition(s) used as combination therapy formulations suitable for administration and prophylactic and/or symptomatic and/or It also includes therapeutic uses. PRIOR ART (KNOWN STATE OF THE ART) Inflammation and immune responses when glucocorticoids are given at pharmacological doses. are natural hormones that prevent or suppress it. Mechanisms of action at the molecular level When examined, free glucocorticoids rapidly transcend the cell membrane and enter the cytoplasm. They appear to bind with high affinity to their specific receptors. This binding modifies transcription and in the final stage the effects expected from the steroid It provides protein synthesis, which ensures its emergence.

Glucocorticoids play an important role in glucose metabolism. Gluconeogenesis in the liver and stimulates glycogenolysis. It reveals the hormones involved in gluconeogenesis, Insulin resistance inhibits glucose reuptake from cells. As a result of these effects blood sugar also increases. Glucocorticoids also affect fat metabolism. protein in muscles Inhibits synthesis and proteinolysis. It also affects bone and mineral metabolism. (Orth DN, Kovacs WJ, DeBold CR. The adrenal cortex. In Williams Textbook of Eiidocrinology.Ed by Wilson ,ID, Foster DW. Philadelphia: WB Saunders Company, 1992;489-53l)i Glucocorticoids mainly stimulate carbohydrate and protein breakdown, They are important regulators of inflammatory responses. They raise blood pressure, from the gut They reduce calcium absorption. Due to its anti-inflammatory and immunosuppressive properties rheumatoid arthritis (RA), inflammatory bowel disease, multiple sclerosis, psoriasis and eczema They are used in the treatment of many diseases such as It has very important cardiovascular, metabolic, immunological and homeostatic functions.

Synthetic glucocorticoids have anti-inflammatory effects and due to these effects, It is used in the treatment of auto-immune diseases such as rheumatoid arthritis. Synthetic The most commonly used glucocorticoids are prednisone and cortisone. Long-term they cause osteoporosis (Taniura, Okinaga, Takami; Glucocorticoid- induced osteoporosis; Biomedecine & Pharmacotherapy Volume 58, Issue 9, November 2004, Pages 500-504) is considered.

Corticosteroids, mainly anti-inflammatory, immunosuppressive and antiproliferative show a triple effect. In the treatment of skin diseases caused by bacteria and fungi steroids, antibacterial and antifungal agents (or appropriate doses of these) There are many treatment modalities such as combinations.

Active substances used in appropriate treatments as corticosteroids, betamethasone, clobetasol, mometasone, anisinonide, halsiiioiiid, desoxymethasone, halomethasone, triaincinolone, fluocinolone, prednicarbate, hydrocortisone, prednisolone, desonide, hydrocortisone, dexamethasone, hydrocortisone, beclamethasone, clobetasone, diflucortolone, Ilumethasone, Ilucortolone, fluticasone, Ilunizolid, budesonide, Iluocinonide and/or pharmaceutical may be selected from among its acceptable derivatives.

Topical steroids, such as corticosteroids, are often used to treat eye infections, especially palpebral or bulbar conjunctiva, cornea, and anterior part of the eyeball responding to steroid therapy It is used in the treatment of inflammatory diseases. General therapeutic applications of steroids among allergic conjunctiva, Acne rosacea, superficial punctate keratitis, superficial iritis and cyclites can be counted. Steroids are also used to prevent foreign body penetration, thermal or chemical for the relief of inflammation in cases of corneal damage caused by burns they are used.

Prednisolone and its derivatives are used as anti-inflammatory or immunosuppressive drugs. synthetic glucocorticoids. Prednisolone, prednisone activated in the liver form and is sometimes used in liver patients. The active ingredient selected from among the corticosteroids is found as a solid particle and many Suspension formulation including auxiliary and active ingredients is mentioned. liquid formulation containing prednisolone is mentioned.

DESCRIPTION OF THE INVENTION The present invention; primary and secondary adrenal insufficiency, acute adrenocortical insufficiency, congenital adrenal hyperplasia, cancer-related hypercalcemia, nonsuppurative thyroiditis, rheumatoid arthritis, including uvenile rheumatoid arthritis) psoriatic arthritis, ankylosing spondylitis, acute gouty arthritis, post-traumatic osteoarthritis, acute non-specific tendosynovitis, acute/subacute bursitis and epicoidylitis, systemic lupus erythematosus, systemic dermatomyositis and acute rheumatoid carditis, pemphigus, erythema multiforme (Stevens-Johnson syndrome) exfoliative dermatitis, bullous dermatitis herpetiformis, severe psoriasis, seborrheic dermatitis and mycosis fungoides, herpes zoster ophthalmicus, iritis, iridocyclitis chorioretinitis, diffuse posterior uveitis and choroiditis, optic neuritis, sympathetic ophthalmia, anterior segment inflammation, allergic conjunctivitis, allergic corneal marginal ulcer and keratitis, bronchial asthma, contact dermatitis, atopic dermatitis, serum sickness, seasonal or perennial allergic rhinitis, drug hypersensitivity, urticarial transfusion reactions and acute non-infectious laryngeal edema, symptomatic sarcoidosis, berylliosis, incurable Löffler syndrome, aspiration pneumonia and necessary anti- Fulminated or disseminated pulmonary tuberculosis with tuberculosis therapy, acquired (autoimmune) hemolytic anemia, secondary thrombocytopenia in adults, erythroblastopenia, congenital hypoplastic anemia, multiple sclerosis, ulcerative colitis and regional enteritis for use in the symptomatic and/or prophylactic and/or therapeutic treatment Suitable for glucocorticoids with anti-inflammatory and immunosuppressive properties of the active substance and/or its pharmaceutically acceptable derivatives as monotherapy used alone and/or in combination with other suitable active agent/s relates to the pharmaceutical composition(s) for which it is used as a treatment.

Another aspect of the present invention is; anti-inflammatory for oral and/or parenteral use and/or appropriate active substance in the glucocorticoid group with immunosuppressive properties where pharmaceutically acceptable derivatives are used alone as monotherapy and/or as a combined treatment of this active substance with other suitable active agent/s. relates to the preparation of the pharmaceutical composition(s) for which it is used.

In the glucocorticoid group with anti-inflammatory and immunosuppressive properties used in the invention Although the appropriate active ingredient is not limited to these; prednisone, prednisolone, methylprednisolone, desonide, fluprednisolone, difluprednate, fluperolone, dexamethasone, betamethasone, clobetasol, clobetasone, diflorazone, halomethasone, ulobetasol, beclomethasone, paramethasone, alclomethasone, fluchlorolone acetonide, flumethasone, fluprednidenj hydrocortisone, thixocortol, budesonide and/or pharmaceutically acceptable derivatives as inethylprednisolone and/or methylprednisolone sodium succinate. is selected.

In the invention, the term "pharmaceutically acceptable derivatives" is defined as pharmaceutically acceptable. Suitable salts, esters, solvates, hydrates, complexes, polymorphs, enantiomers, prodrugs, acid addition salts, analogs, isomers, racemates, amides, enantiomer salts, basic salts, conjugates, tautomers, anhydrates, anhydrides, bases, one or more of acids, ethers, crystalline and amorphous forms or free forms is expressed.

Pharmaceutical composition/s prepared for oral administration in solid or liquid dosage forms it could be. These dosage forms are; tablet (uncoated, chewable, mouth soluble, dispersible, water dispersible, film coated, single layer, double layer, intestinal opening coated, mini tablet, controlled release, sustained release, immediate release, extended release, delayed release, modified release, buccal), capsule (hard, soft, enteric coated, film coated, controlled release, sustained release, immediate release, extended release, delayed release release, modified release), powder, granule, caplet, disc, mouth soluble film, bulk powder (multi dosed), pellet, sachet, water-dispersible powder, water-dispersible granule, effervescent tablet, effervescent granule, effervescent powder, microcapsule, dental tablets, pilula, syrup, solution, as a dosage form such as suspension, elixir, drops, position, emulsion, or spray. can be formulated.

In the present invention, tablet(s) prepared for oral use have one or more coatings. may contain.

coated tablets; The active ingredient is usually in the core, partially in the core and It is prepared in the form of formulas containing partially coating or only coating.

Coating materials must be physiologically harmless and incompatible with the active substance. should not be.

Coating types ; sugar coating, film coating and intestinal soluble (enteric) coating can be counted as

Sugar-coated tablets are compressed tablets having a coating consisting of sugar. are tablets. The coating may be colored and may have an offensive taste or coating of active substances with odor and sensitive to oxidation It is extremely useful in terms of protecting materials.

Film-coated tablets are a thin film applied using a water-soluble material. Compressed tablets coated with a layer or film. In line with this, the movie Maker A range of polymeric materials can be used with properties Film coatings, sugar Although it has the same general properties as the coatings, it is necessary for the coating process. It brings with it the important additional advantage of significantly reducing the time.

Purposes of Coating; o Protection of the active substance against light, oxygen and moisture o Masking off the offending odor and taste of the active ingredient o Correction of the aesthetic appearance of the tablet 0 Obtaining colored tablets with very little dyestuff o Increasing the easy swallowing of the tablet by the patient 0 Increased mechanical strength during production, packaging and transportation - Protection of the active substance against digestive secretions 0 Avoidance of side effects, eg stomach irritation o Facilitating the identification of the drug, thus ensuring safety in drug use. increase o Increasing the stability of the active ingredient o Editing of controlled release characteristics can be counted as

The pharmaceutical formulation of the invention may contain one or more layers. Sufficient therapeutic control the release of the drug in order to ensure the effect and minimize the side effects. alternating, controlled, extended, continuous, immediate or a delayed-release pharmaceutical formulated with one or more of the dosage forms can be done.

In delayed release systems, the release of the active substance from the system is in a certain region. is happening. It is generally used for enteric coated tablets.

To increase the stability of the enteric coating formulation, to prevent acid-induced degradation. It is expressed as the substance or substance mixture used for These enteric coatings Before it starts to decompose, it resists stomach acid and also It provides a slow drug release in the upper part of the small intestine or in the upper part of the small intestine.

Direct compression, wet or dry granulation in the preparation of tablet(s) of the invention applicable.

Direct compression of the powdered material without disturbing the physical structure of the material. It is obtained by compression. Widely used as a direct compaction tool The excipient studied in this way is microcrystalline cellulose (Avicel, FMC).

Many techniques are used in the preparation of dosage forms. one of them granulation method. Granulation; as the growth of fine dust particles is defined. Granulation for pharmaceutical purposes; a preparation for tableting This is the stage of filling hard gelatin capsules or granules as a final product. It is also applied for the purpose of being placed in a package.

The purpose of the granulation is to give the unit drug % of the particles of the powder substance participating in the mixture. is to create a unit of weight that will be equivalent to the quantities. Pharmaceutical powder mixes (active substance or auxiliary substances) in a unit by preventing their separation. It is necessary to ensure that they remain in a homogeneous form, this is achieved by granulation. possible.

The methods to be chosen in granulation can be classified in 3 main categories: wet granulation, dry granulation and other granulation methods.

Age Granulation: In the wet granulation method, high speed fluidized bed granulation, spray drying and extrusion pelletizing methods are used. Mourning In granulation, the active ingredient and the binder (solution) are mixed for a certain period of time. sieved and dried in a fluidized bed dryer. This dried mixture is the other filling. It is mixed with the ingredients until it reaches a certain homogeneity. My wife's last 3-5 slider is added in minutes. Samples are taken from the final mixture obtained and sent to the laboratory. It is sent for tablet compression or for the desired pharmaceutical form according to the laboratory result. stages can be passed.

Age granulation methods: 1. Age granulation method (Classical method) 2. Granulation by fluidized bed method 3. Granulation by Spray-Drying method 4. Microgranulation method . Extrusion-Spheronization method 6. Method of preparing granules with high-level mixers The wet granulation process is as follows: - Grinding the active ingredient (if necessary), - Mixing with powder substances, ° Ensuring curing of the particles of the powder mixture with the addition of binder, (This The process is called granulation.) - Screening of agglomerated particles as wet, - Drying of the sifted powder mixture is common in the drying process using bed dryers, - Dry grinding after drying, - Homogenizing in double conical or V type mixers - Adding lubricant to this resulting mixture and mixing for another 5 minutes, (This the mixture is called the tinal product) - It is the transition to tablet pressing or the stages for the desired pharmaceutical form.

Dry Granulation: In the dry granulation method, pre-compression and inter-roll compression methods are used. In sand granulation, it is usually 1/3 of the lubricant is mixed with other powder mixtures. This is because dust gets into the cylinders. prevents it from sticking. The remainder of the lubricant is added to the mix after dry granulation. and stirred for 3-5 minutes. Samples are taken from the final mixture formed after the mixture and It is sent to the laboratory for various tests. According to the laboratory results, tablet compression or The steps can be passed for the desired pharmaceutical form.

capsules; gelatin, cellulose esters, polyvinyl alcohol etc. for single dose drug administration. They are containers made of one of the materials. Doses, solid and partial substances into capsules, Liquid drugs that do not dissolve the capsule can be placed. Capsules are generally divided into two; rigid/two-piece capsules and soft capsules.

Hard capsules consist of two parts: the container and the lid part. Bitter taste, swallowed capsules of difficult, air-perishable powders and drugs that are required to be rapidly absorbed. provided in. The main ingredient of hard gelatin capsules is a macromolecular It consists of high-value gelatin, which is a protein. Hard gelatin capsules gelatin, gum arabic, It is prepared from a mixture of paint and water with special techniques and special machines. hard capsules It is prepared by dipping method. The principle of this method is made of stainless steel on the surface of these rods by immersing them in the melted capsule wall solution. is the formation of the capsule wall film. Gelatin, dyes, preservatives and water, hard They are the substances that make up the gelatin capsule wall.

Hard capsules can be filled in powder, granule, pellet, tablet, liquid, and semi-solid forms.

There are two basic requirements for any formulation filled into capsules. The formulation must be filled in the correct dose and the active substance is released from the capsule for the treatment of the patient. should be released in sufficient quantity. For the preparation of hard gelatin capsule formulations active ingredient, fillers, flow-improving agents, glidants, anti-friction inhibitors, lubricants, dispersants, surfactants are used.

Soft capsules: single gelatin prepared with mixtures of glycerin, sorbitol, gum arabic and water. They are round, elliptical and tube-shaped capsules consisting of pieces. Required items After being placed, they are closed to not open. Soft capsules, gelatin of liquid1 content It is prepared by enclosing it with the capsule wall. They are more flexible than hard capsules.

Soft capsules are round, oval, oblong (oblong stick) or tubular they may be. They consist of one piece. Soft gelatin capsules are usually included in solution or Liquid drug forms in suspension form are filled. However, semi-solids and powders are also can be filled. Production of soft capsules, insoluble substances, low-dose active substances, highly active compounds, oxygen sensitive substances, bad taste suitable for materials. In the production of soft gelatin capsules, the capsule wall a successive sequence of preparation, filling of the material and closure of the capsule. consists of the name.

Pharmaceutical composition(s) prepared for parenteral administration, ampoule, vial, infusion or It can be in dosage forms containing lyophilized powder.

Parenteral injection is intraperitoneal, intravenous, infusion, intramuscular, subcutaneous, or can be administered intradermally.

The pharmaceutical formulation prepared in the present invention; pharmaceutically acceptable In addition to suitable active substances, binder, dispersant, filler, buffering agent, surfactant, lubricant, glidant, diluent, preservative agent, flavoring agent, sweetening agent, viscosity increasing agent, antifoaming agent, solubility increasing agent, antistatic agent, wetting agent, pH adjusting agent, colorant agent, coating agent, solvent, softening agent, emulsifier, carrier, permeability substance, antioxidant, chelating agent, alkalizing agent, photoprotective agent, thickener agent, isotonia adjusting agent, gelling agent, microbial preservative, hardener agent, sivag, release controlling agent, plasticizer, antiadherent, film-forming agent, opacifier agent, wetting agent, granulation solvent and stabilizer. describes a composition that may contain one or more selected excipients.

The term "binding agent" in the invention; keeping the ingredients together, tablets, pellets or ensuring that the granules are formulated with the required mechanical strength and low active dosage. expressed as substances or mixtures of substances used to give volume to units of is being done. As a binding agent; pregelatinized corn starch, pregelatinized starch, hydroxypropyl starch, gelatin, microcrystalline cellulose, cellulose, gums, polyvinyl pyrrolidone, polymethacrylates, sodium carboxymethyl cellulose, starch, paraffins, stearic acid, gums, methyl cellulose, ethyl cellulose, polyethyleneglycol, magnesium aluminum silicate, carboxy methylcellulose, hydroxy propylcellulose, hydroxy ethylcellulose, propylene glycol, polyoxyethylene- polypropylene copolymer, polyethylene ester, polyethylene sorbitan ester, polyethylene oxide, polysaccharides, polaxamers, alginic acids, collagen, albumin, crospovidone, povidone, Copovidone, maltodextrin, hypromellose or mixtures of these can be used.

In the invention, the term "dispersant" means that the dosage form can be easily and quickly dissolved in water. It is expressed as substances that allow it to disperse. As a dispersant; agar agar, calcium carbonate, sodium carbonate, alginic acid, potato starch, corn starch, wheat Starches such as starch, pregelatinized starch, sodium starch glycolate, microcrystalline cellulose, cross-linked polyvinyl pyrrolidone, sodium alginate, hydroxypropyl cellulose, cross bound hydroxypropyl cellulose, croscarmellose sodium, clay, ion exchange resin, crospovidone, xylitol, D-sorbitol, D-mannitol, lactose, sucrose, urea, high molecular weight polymers, povidone, alginic acid, xanthan gum, colloidal silicon dioxide or their mixes can be used.

The term "filler" in the invention; practical, patient for the production of tablets or capsules as a substance or a mixture of substances used to be in a suitable size for its use is expressed. As a filler; talc, lactose, sucrose, dextrin, mannitol, lactilol, lactitol, xylitol, sorbitol, isomalt, microcrystalline cellulose, powdered cellulose, dextrose, dextrate, pregelatinized starch, modified starch, corn starch, lactose anhydrous, lactose monohydrate, dibasic calcium phosphate, silicic acid, kaolin, hydroxy propyl methylcellulose, tribasic calcium phosphate, polyhydric alcohols or cellulose ethers, calcium hydrogen phosphate dihydrate, calcium sulfate trihydrate, cellulose calcium sulfate, calcium sulfate dihydrate, maltodextrin, calcium carbonate, kaolin, sodium hydroxide or their mixtures can be used.

In the invention, the term "buffering agent" is used to regulate the acidity and basicity of the composition. referred to as items. As a buffering agent; citric acid anhydrous, sodium citrate dihydrate, sodium phosphate, sodium dihydrogen phosphate, potassium citrate, phosphoric acid, ammonium hydroxide, citric acid, diisopropanolamine, sodium carbonate, sodium silicate, disodium orthophosphate, calcium carbonate, magnesium carbonate, magnesium hydroxide, magnesium aluminate, diethanol amine, sodium alginate, ethylenediamine, meglumine, hydrochloric acid, lactic acid, sodium citrate, sodium hydroxide, triethanolamine, trolamine, sodium benzoate, sodium hydrogen carbonate or their mixtures can be used.

In the invention, the term "surfactant" is applied when dissolved in water or an aqueous solution. It refers to the chemical compound that affects the voltage. As a surfactant polysorbates, sodiumlauryl sulfate, sodium stearyl fumarate, non-ionic polyoxyethylene polyoxypropylene co-polymer, hexadecyl trimethyl ammonium bromide, alkyl polyethylene oxide, poloxamers, octyl glucoside, sugar esters and glycerides of fatty acids, dodecyl betaine, dodecyl dimethylamine oxide, polyoxyl stearate, sodium stearate, polyethylene glycols, L-leucine, alkyl benzene sulfonate, fatty acids, quaternary ammonium compounds or mixtures thereof can be used.

"Lubricant" in the invention is the flow of a powder mixture that reduces or inhibits friction. It is expressed as agent or agent mixtures that improve its properties. lubricant aspect; talc, calcium stearate, magnesium stearate, aluminum stearate, polyethylene glycol, tristearin, stearic acid, sodium lauryl sulfate, magnesium lauryl sulfate, colloidal silicon dioxide, stearic acid, sodium stearyl fumarate, polyoxyethylene glycol, oleic acid, tripalmityl, potassium oleate, hydrogenated vegetable oils, leucine, alanine, glycine, caprylic acid, glyceryl behenate, glyceryl palmitostearate, sodium benzoate, sodium acetate, fumaric acid, zinc stearate, zinc oleate, zinc palmitate, paraffins, fatty alcohols or their mixtures can be used.

The term "glidant" in the invention; Tablet pressing immediately allows the flow of material into the matrix space. It is expressed as a substance with extra small particles and low density that facilitates it.

As a glidant; talc, magnesium stearate, hydrogenated vegetable oil, calcium stearate, stearic acid, colloidal silicon dioxide, sodium stearylfumate, polyoxyethyleneglycol, leucine, sodium benzoate, sodium chloride, sodium acetate, sodium fumarate, silica, colloidal anhydrous silica, polyethyleneglycol, cellulose derivatives, starch or their mixtures can be used.

The term "diluent" in the invention; practical, patient for the production of tablets or capsules as a substance or a mixture of substances used to be in a suitable size for its use is expressed. As a diluent; lactose, maltose, sucrose, dextrin, mannitol, lactylol, xylitol, sorbitol, isomalt, microcrystalline cellulose, dextrose, dextrate, pregelatinized starch, modified starch, corn starch, lactose anhydrous, lactose monohydrate, dibasic calcium phosphate, hydroxy propyl methylcellulose, tribasic calcium phosphate, polyhydric alcohols or cellulose ethers, calcium hydrogen phosphate dihydrate, calcium sulfate trihydrate, calcium sulfate dihydrate, maltodextrin, calcium carbonate, kaolin, sodium hydroxide or their mixes can be used.

The term "preservative" in the invention; water and water-soluble, oil and fat-soluble substances It is expressed as substances that provide protection against microorganisms.

2-phenoxyethanol, sodium benzoate, benzoic acid, benzyl alcohol, ethylenediaminetetraacetic acid, sodium methyl parahydroxy benzoate, sodium propyl para hydroxy benzoate, sorbic acid, potassium sorbate, benzetonium chloride, chlorocresol, benzalkonium chloride, butyl paraben, methyl paraben, propyl paraben, ethyl paraben, butyl hydroxy anisole (BHA), butyl hydroxy toluene (BHT), calcium acetate, citric acid, disodium edetate, glycerin, propyl gallate, sodium bisulfite, sodium citrate, sodium metabisulfite, boric acid, sorbic acid, sodium propionate, propylene glycol or their mixtures can be used.

In the invention, the term "flavoring agent" is defined as substances used to add flavoring to the mixture. is being done. As a flavoring agent; natural aroma oils (peppermint oil, wintergreen oil, parsley oil, orange oil, grape, citrus, grapefruit, lemon oil, etc.), orange flavor, banana flavor, peach flavor, grapefruit flavor, lemon flavor, apple flavor, strawberry flavor, vanilla flavor, mint flavor, tutti-furitti flavor, raspberry flavor, menthol, menthane, anethole, cinnamon, methyl salicylate, eucalyptal, sage, blackberry, citrus fruits or mixtures of these can be used.

As a "flavoring agent" in the invention; sodium saccharin, sucrose, D-glucose, galactose, xylose, maltose, maltodextrin, maltol, erythritol, lactitol, isomalt, isomaltol, corn syrup, D- tryptophan, glycyrrhizic acid, monoammonium glycyrrhizinate, fructose, maltitol, dextrose, sucrose, xylitol, sorbitol, mannitol, lactose, aspartame, acesulfame potassium, neohesperidin dihydrochalcone, sucralose, sodium cyclamate or their mixtures can be used.

In the invention, the term "viscosity increasing agent" means that it increases the thickness of the liquid and causes it to flow slowly. It is expressed as an agent or agent mixtures that provide Viscosity increasing agent aspect; xanthan gum, guar gum, acacia, povidone, alginic acid, ethylcellulose, gelatin, hydroxyethyl cellulose, hydroxypropyl cellulose, cetyl alcohol, polyvinyl pyrrolidone, hydroxy propyl methyl cellulose, polydextrose, carrageenan, methyl cellulose, sucrose, sorbitol, xylitol, hydroxypropyl methylcellulose, polyvinyl alcohol, ketaryl alcohol, colloidal silicon dioxide or mixtures of these can be used.

In the invention, the term "antifoaming agent" refers to the initiation of the foaming reaction while the product is stored. as substances that stabilize the product against the water in the existing system by preventing is expressed. As antifoaming agent; simethicone emulsion, dimethylsiloxane, silicone oil, monosodium carbonate, anhydrous trimagnesium dicitrate or mixtures thereof can be used. Antifoaming agent directly into effervescent granulated or external phase tablet It can be mixed with other excipients in powder form or made into both effervescent granules and tablets. It can be added to the excipient mixture by portioning.

As a solubilizing agent in the invention; sodium caseinate, polysorbate, methacrylic acid copolymer or mixtures thereof can be used.

The term "antistatic agent" in the invention; to reduce or eliminate static electricity in the content It is expressed as the substance or substance mixture used. The aforementioned antistatic as an agent; long Chain aliphatic aines and amides, quaternary ammonium salts, phosphoric acid esters, polyethylene glycol esters, polyols, mono and diglyceride, fatty acid esters or mixtures of these can be used.

In the invention, the term "wetting agent" is readily available in the dispersion medium of hydrophobic drugs. It is expressed as substances used to help dispersal. slacker as stubborn; sodium lauryl sulfate, sodium docusate, polysorbates, sorbitan monolaurate, 0kt0xinol-9, nonoxynol-10, poloxamers, sodium carboxyinethyl cellulose, bentonite, benzalkonium chloride, tetradecyltrimethyl ammonium bromide, cetylpyridinium chloride, glyceryl monostearate, macrogol cetostearyl ether, sorbitan tristearate, aluminium magnesium silicate or mixtures of these can be used.

In the invention, the term "pH adjusting agent" is used to regulate the acidity and basicity of the composition. referred to as items. As a pH adjusting agent; citric acid anhydrous, sodium citrate dihydrate, sodium phosphate, sodium dihydrogen phosphate, potassium citrate, phosphoric acid, ammonium hydroxide, citric acid, diisopropanolamine, sodium carbonate, sodium silicate, disodium orthophosphate, calcium carbonate, magnesium carbonate, magnesium hydroxide, magnesium aluminate, diethanol amine, sodium alginate, ethylenediamine, meglumine, hydrochloric acid, lactic acid, sodium citrate, sodium hydroxide, sodium chloride, triethanolamine, trolamine, sodium benzoate, sodium hydrogen carbonate or their mixtures can be used.

In the invention, the term "coloring agent" is a pleasant-looking and intermediate between the two formulations. They are expressed as substances that provide optical discrimination. Colorant as substances, but not limited to, yellow iron oxide, red iron oxide such as iron oxide pigments, ß-carotene, red beet powder, chlorophyll, tartrazine, yellow orange, quinoline yellow, erythrosine, titanium dioxide pigments, caramel, sunset yellow or mixtures of these can be used.

In the invention, the term "coating agent" describes the formulation content by moisture in the air. to protect against degradation and to facilitate swallowing unpleasant-tasting forms. It is expressed as the substance or substance mixture used. Coating agent aspect; methyl cellulose, hydroxyethylcellulose, hydroxybutylcellulose, hydroxypropylmethylcellulose, ethyl cellulose, hydroxymethyl cellulose, hydroxypropylcellulose, carboxymethylethylcellulose, sodium carboxymethyl amylopectin, polyvinyl acetate phthalate, polyoxyethylene glycol, polyvinyl alcohol (opadry varieties), polyviryl acetal diethyl aminoacetate, aminoalkyl methacrylate copolymer, methacrylic acid copolymer, hydroxypropyl methyl cellulose acetate, dioxy methyl cellulose succinate, carboxy methyl ethyl cellulose, polyacrylic acids, methacrylic acid copolymers, methyl acrylate, ethylacrylate, methylmethacrylate, ethylmethacrylate, acrylic and methacrylic acid esters, hypromellose, hypromellose phthalate, hypromellose acetate succinate, hydroxymethyl cellulose succinate acetate, cellulose butyrate phthalate, cellulose hydrogen phthalate, cellulose propyanate phthalate, cellulose acetate phthalate, hydroxypropylmeth[cellulose phthalate, cellulose acetate trimellitate, gelatin, celak, castor oil, chitosan, alginic acid, Irish moss, galactomanones, tragacanth, Indian glue, gum arabic, guar gum, xanthan gum or their mixtures can be used. Such as purified water, ethyl alcohol, methyl alcohol, isopropyl alcohol, butyl alcohol as a solvent. alcohols, acetone, diacetone, polyols, polyethers, esters, alkyl ketones, methylene chloride, methyl acetate, ethyl acetate, isopropyl acetate, castor oil, ethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol monoethyl ether, dimethyl sulfoxide, dimethyl formamide, tetrahydrofuran or mixtures thereof may be used.

The term "softening agent" in the invention; water by forming a thin film on the skin It is expressed as substances that prevent it from flying. Vaseline as an emollient, solid petrolatum, liquid paraffin, sorbitol, glycerin, hydrocarbons, lanolin, waxes, fatty acids, cetyl alcohol, octyldodecanol, caprylic/capric triglyceride, cetyl stearyl alcohol, cocoa butter, diisopropyl adipate, glycerine, polyhydric alcohols and polyether derivatives, polyhydric alcohol esters, glyceryl monooleate, glyceryl stearate, linoleic acid, oleic acid, polypropylene glycol-1S stearyl ether (PPG-1S stearyl ether), polyethylene glycol, polyoxyethylene glycol fatty alcohol ethers, polyoxypropylene stearyl ether, propylene glycol stearate, stearic acid, stearyl alcohol, phospholipids, lecithin, steorols, cholesterol, cholesterol fatty acid esters and amides, urea, glyceryl monostearate, isopropyl iniristate, isopropyl palinitate, ketostearyl alcohol, diinethicone, mineral oils, white solid paraffin, cetearyl alcohol or their mixtures can be used. Moreover herbal emollient such as castor oil, coconut oil, olive oil and vegetable waxes agents can also be used.

In the invention, the term "emulsifier" means a homogeneous mixture between two immiscible liquid phases. are expressed as substances that provide dispersion. Polyethylene glycol as emulsifier stearate, polysorbate, polyglyceryl oleate, polyoxyethylene lauryl ether, ethoxylated lanolin, stearyl alcohol, cetostearyl alcohol, macrogol cetostearyl, glyceryl monostearate, cetyl alcohol, polyoxyethylene lauryl alcohol, polyoxy ethylene sorbitan monostearate, polyoxyethylene stearate, sorbitan monostearate, propylene glycol stearate, aluminum starch octenylsuccinate, ammonium hydroxide, a white wax, a synthetic wax, carbomer, cetearyl alcohol, cyclomethicone, diglycerides, dimethicone, disodium monooleamido sulfosuccinate, pentaerythritol, glycerides, glyceryl monooleate, glyceryl stearate, lanolin, hydrogenated magnesium stearate, mineral oil, monoglycerides, polyethylene glycol, polyethylene glycol distearate, polyethylene glycol inonocetyl ether, polyethylene glycol monostearate, polyoxyethylene glycol, polyoxyl cetostearyl ether, polyoxyl stearate, simethicone, sorbitan inonolaurate, sorbitan monooleate, sorbitan inonopalinitate, sorbitan palinitate, stearic acid, trietailiolainii or sodium lauryl sulfates or their mixtures can be used.

In the invention, propylene glycol, purified water, castor oil, diisopropyl adipate, ethoxylated alcohol, fatty alcohol citrate, glycerine, hexylene glycol, isopropyl alcohol, isopropyl myristate, isopropyl palmitate, mineral oil, phosphoric acid, polyethylene terephthalate glycol, polyethylene glycol, polyethylene glycol moiiostearate, polyoxyl ketostearyl ether, polyoxypropylene stearyl ether, polysorbate, octyldodecanol, propylene carbonate, saturated fatty acid triglycerides, benzoic acid, ethanol or mixtures thereof may be used.

In the invention, the term "permeabilizing agent" refers to a substance that facilitates the penetration of saliva and thus creating a hydrophilic network that contributes to better dispersion of the tablet. referred to as items. Precipitated silicas as permeation agent, inaltodextrins, β-cyclodextrins or mixtures thereof can be used.

In the invention, the term “antioxidant” prevents oxidation caused by free radicals, are substances that have the ability to capture and stabilize free radicals. is being done. As an antioxidant; tocopherol (vitamin E), ascorbic acid (vitamin C), A vitamin, vitamins such as vitamin K, carotenoids, carotenes (eg oi-carotene, ß- carotene, lycopene, lutein, zeaxanthin), minerals (Se, Zn), butyl hydroxy anisole (BHA), butyl hydroxy toluene (BHT), ethylgalate, propylgalate, dodecylgalate, taurine, organosulfur compounds (allium, allyl sulfide, indoles), low molecular weight antioxidants (GSH-Px, uric acid) or mixtures of these can be used.

EDTA (ethylene diamine tetraacetic acid), disodium EDTA as chelating agent in the invention (disodium ethylene diamiii tetraacetic acid) or calcium EDTA (calcium ethylene diamine) tetraacetic acid) or mixtures thereof can be used.

As an alkalizing agent in the invention; sodium carbonate, sodium hydrogen carbonate, sodium hydroxide, sodium silicate, primary amines, secondary amines, tertiary amines, cyclic amines, calcium glycerophosphate, calcium gluconate, calcium acetate, N,N° dibenzylethylenediamine, diethanolamine, ethylenediamine, meglumine, disodium hydrogen orthophosphate, sodium aluminate, calcium carbonate, calcium hydroxide, magnesium carbonate, magnesium hydroxide, magnesium sulfate, monosodium glutamate, polakrillin sodium, sodium alginate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, magnesium acetate, magnesium silicate, magnesium aluminate, magnesium oxide or mixtures of these can be used.

As a photoprotective agent in the invention; iron oxide derivatives, metal oxides, titanium oxide or mixtures of these can be used.

In the invention, the term "thickening agent" refers to the resistance of formulations to various pressures and forces. are expressed as substances used for strengthening. thickening agent aspect; cetyl alcohol, aluminum stearate, dimethicone, cetearyl alcohol, stearyl alcohol, gum arabic, gum tragacanth, alginate, carrageenan, xanthan gum, guar gum, cetostearyl alcohol, cetyl esters wax, dextrin, glyceryl monostearate, hydroxypropyl cellulose, kaolin, polyethylene white petrolatum, propylene glycol stearate, starch, wax, white wax, bentonite, beeswax, white beeswax, synthetic wax, paraffin, white solid paraffin, white soft paraffin, solid Vaseline, pectin, carbomer, polyvinylpyrrolidone or their mixtures can be used.

In the invention, the term "isotonia adjusting agent" means the same osmotic pressure as the standard reference substance. referred to as substances. As the aforementioned isotonia adjusting agent; sodium chloride, mannitol, sorbitol, boric acid, potassium nitrate, glucose or their mixes can be used.

In the invention, carbopol, carbomer, hydroxy propylmethylcellulose, methylcellulose, sodium carboxymethylcellulose, polyacrylate polymers or their mixes can be used.

In the invention, the term "microbial preservative" protects against microbial activity. referred to as items. As the aforementioned microbial preservative; sodium benzoate, sodium methyl para hydroxybenzoate, sodium propyl para hydroxybenzoate, benzalkonium chloride, boric acid, sorbic acid, ethanol or their mixtures can be used.

In the invention, “hardening agent; The term means formulations against various pressures and forces. are expressed as substances used for strengthening. As a hardening agent; cetyl alcohol, aluminum stearate, dimethicone, cetearyl alcohol, stearyl alcohol, gum arabic, tragacanth gum, alginate, carrageenan, xanthan gum, guar gum, cetostearyl alcohol, cetyl esters wax, dextrin, glyceryl monostearate, hydroxypropyl cellulose, kaolin, polyethylene white petrolatum, propylene glycol stearate, starch, wax, white wax, bentonite, beeswax, white beeswax, synthetic wax, paraffin, white solid paraffin, solid petrolatum, pectin, carbomer, polyvinylpyrrolidone or mixtures thereof can be used.

As sivag in the invention; macrogol derivatives, petrolatum, wax modified vaseline, liquid petrolatum, white petrolatum, lanolin or lanolin derivatives, castor oil, coconut oil, olive oil, vegetable oils such as cottonseed oil, polyethylene glycol, paraffin, anhydrous, white soft paraffin or their mixtures can be used, As "release controlling agent" in the invention; polyvinyl acetate phthalate, polyethylene glycol-polyvinyl alcohol copolymer, polyacrylic acid derivatives, polysaccharide derivatives, methacrylate polymer, polymethacrylate, ethyl methacrylate copolymer, methacrylic acid-methylmethacrylate copolymer, methacrylic acid-ethyl acrylate copolymer, polylactic acid, polylactic acid copolymer, polyvinylpyrrolidone, polyvinylalcohol, glyceride, polyethylene oxide, glyceryl behenate, methacrylic acid copolymer, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose acetate, carboxy methyl ethyl cellulose, sodium carboxy methyl cellulose, ethyl cellulose, methyl acrylate, ethylacrylate, methylmethacrylate, ethylmethacrylate, acrylic and methacrylic acid esters, sodium alginate, hypromellose phthalate, hypromellose acetate succinate, cellulose butyrate phthalate, cellulose hydrogen phthalate, cellulose propyanate phthalate, cellulose acetate phthalate, cellulose acetate Trimelitate, gelatin, celak, xanthan gum or mixtures of these can be used.

In the invention, the term "plasticizer" is used to increase the flexibility of the coating, reduce the risk of film breakage. It is expressed as substances used to reduce the film and increase the adhesion of the film to the core. They must be compatible with the polymer and not be volatile.

As a plasticizer; polyethylene glycols (Macrogol), glycerin, propylene glycol, acetyl citrate, arnyl oleate, iniristyl acetate, butyl oleate, butyl stearate, triacetin, diethylphthalate, acetylated monoglycerides or mixtures thereof may be used.

In the invention, the term "antiadherent" refers to substances that prevent the formation of a rough tablet surface. is expressed. As an antiadherent; talc, colloidal silicon dioxide (Aerosil, Syloid, Cab-O-Sil), magnesium stearate, corn starch, magnesium trisilicate or their mixes can be used.

In the invention, the term "film-forming agent" refers to the use of a binder as a film, eg film or film. It is expressed as the necessary components to create it. As a film making agent; polyvinyl alcohol-partially hydrolyzed, methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, polyethylene glycol, polyethylene oxide, Macrogol, gelatin or their mixtures can be used.

In the invention, the term "opacifying agent" refers to the addition of the desired system to make it opaque. referred to as items. As an opacifying agent; titanium dioxide, calcium carbonate, zinc acetate, aluminum stearate, zinc stearate or mixtures thereof can be used.

The term "moisturizing agent" in the invention; the amount of moisture between the preparation and the air. are referred to as regulating and controlling substances. moisturizing agent aspect; glycerin, sorbitol, propylene glycol, urea, colloidal substances, liquid paraffin, petrolatum (petrolatum), liquid petrolatum, cellulose and cellulose-containing substances, gums (tragacanth), some electrolytes (Al velocities, mercury salts borax) or their mixtures can be used.

In the invention, purified water, ethyl alcohol, methyl alcohol, isopropyl as granulation solvent Alcohols such as alcohol, butyl alcohol, methylene chloride or their mixtures can be used.

The term "stabilizer" in the invention; prevents crystallization or phase separation when added referred to as items. Benzoic acid, edetic acid, salicylic acid as stabilizer, sorbic acid, sodium dehydroacetate, tocopherol, butyleninis hydroxyanisole, butylated hydroxytoluene, propylgallate, castor oil, oleyl alcohol, poloxamer and poloxamines (polyoxyethylene and polyoxypropylene block copolymer), xanthan gum, sorbitan oil ethoxylated esters of acids, polysorbates such as polysorbate 80 or Tween 80, ethoxylated mono- and diglycerides, ethoxylated lipids, ethoxylated fatty alcohols or fatty acids, diacetyl phosphate, phosphatidyl glycerol, saturated or unsaturated fatty acids, sodium cholate, sodium glycolate, sodium taurocholate, paraoxybenzoic acid, ethylene diamine tetraacetic acid (EDTA), diethylene triamine penta acetic acid or mixtures thereof can be used.

Appropriate active ingredient and/or pharmaceutically acceptable derivatives of the present invention. the amount of Prednisolone in pharmaceutical compositions containing; 0.1-800mg preferably 4ing, Sing and It is 16mg, depending on the individual needs of the patient and the assessment of the specialist. is being set.

The invention is mainly used for oral and/or parenteral use as anti-inflammatory and Prednizoloii and/or glucocorticoid group with immunosuppressive properties where pharmaceutically acceptable derivatives are used alone as monotherapy and/or as a combined treatment of this active substance with other suitable active agent/s. relates to the preparation of the pharmaceutical composition(s) for which it is used. Invention for oral administration The pharmaceutical composition(s) prepared should preferably be in the form of tablets and/or capsules. is fundamental. Another feature of the invention is pharmaceutical preparation for parenteral administration. its composition/s are in the form of ampoules. Thus obtained pharmaceutical formulation/s surprisingly very stable behavior in terms of physical and chemical stability has exhibited. In addition, to provide adequate therapeutic effect and to minimize side effects. They have been found to be surprisingly effective for

Claims (7)

REQUESTS . Pharmaceutical composition in which appropriate active ingredient and/or pharmaceutically acceptable derivatives from the anti-inflammatory and immunosuppressive glucocorticoid group for oral and/or parenteral use are used alone as monotherapy and/or this active substance is used in combination with other appropriate active agent/s It is related to the preparation of /s. It is a pharmaceutical composition/s as in claim 1 and its feature is; The appropriate active substance in the glucocorticoid group with anti-inflammatory and immunosuppressive properties is prednisone, prednisolone, methylprednisolone, desonide, fluprednisolone, difluprednat, fluperolone, dexamethasone, betamethasone, clobetasol, clobetazone, hal, clobetasolone, fluobetasolone, fluobetasolone, fluomethasone, fluobetasolone, fluomethasone, fluomethasone is selected from fluprednia, hydrocortisone, thixocortol, budesonide and/or pharmaceutically acceptable derivatives. . It is the pharmaceutical composition/s as in the request. Its feature is; The appropriate active ingredient in the glucocorticoid group with anti-inflammatory and immunosuppressive properties is preferably inethylprednisolone and/or methylprednisolone sodium succinate. . It is a pharmaceutical composition/s as in claim 1 and its feature is; tablet (uncoated, chewable, orally soluble, dispersible, water-dispersible, film-coated, single-layer, bi-layer, intestinal release coated, mini-tablet, controlled-release, sustained-release, immediate-release, extended-release, delayed-release, modified-release, buccal ), capsule (hard, soft, enteric-coated, film-coated, controlled-release, sustained-release, immediate-release, extended-release, delayed-release, modified-release), powder, granule, caplet, disc, oral soluble film, bulk powder (multidose) ), pellet, sachet, water-dispersible powder, water-dispersible granule, effervescent tablet, effervescent granule, effervescent powder, microcapsule, dental tablets, pilula, syrup, solution, suspension, elixir, drops, position, emulsion, spray, ampoule, vial, comprising one or more pharmaceutical dosage forms selected from infusion or lyophilized powder. . It is a pharmaceutical composition/s as in claim 1 and its feature is; The pharmaceutical composition(s) prepared for oral use is preferably in the form of tablets and/or capsules. . It is a pharmaceutical composition/s as in claim 11 and its feature is; The pharmaceutical composition(s) prepared for parenteral administration is preferably in ampoule form. 7. It is a pharmaceutical composition/s according to any of the above claims and its feature is; The amount of prednisolone in pharmaceutical compositions containing prednisolone and/or its pharmaceutically acceptable derivatives is 0.1-800mg. It is a pharmaceutical composition/s according to any of the above claims and its feature is; primary and secondary adrenal insufficiency, acute adrenocortical insufficiency, congenital adrenal hyperplasia, cancer-related hypercalcemia, nonsuppurative thyroiditis, rheumatoid arthritis, psoriatic arthritis (including juvenile rheumatoid arthritis), ankylosing spondylitis, acute gouty arthritis, post-traumatic osteoarthritis, acute non-traumatic osteoarthritis tendosynovitis, acute/subacute bursitis and epicondylitis, systemic lupus erythematosus, systemic dermatomyositis and acute rheumatoid carditis, pemphigus, erytheina multiform (Stevens-Johnson syndrome) exfoliative dermatitis, bullous derrnatitis herpetifoimis, severe psoriasis and ophthalmic dermatitis, seborrheic dermatitis , iritis, iridocyclitis chorioretinitis, diffuse posterior uveitis and choroiditis, optic neuritis, sympathetic ophthalmia, anterior segment inflammation, allergic conjunctivitis, allergic cornea] marginal ulcer and keratitis, bronchial asthma, contact dermatitis, atopic dermatitis, serum sickness, seasonal or perennial allergic rhinitis, hypersensitivity to drugs, urticarial transfusion ion reactions and acute non-infectious laryngeal edema, symptomatic sarcoidosis, berylliosis, incurable Löffler syndrome, aspiration pneumonia and fulminated or disseminated pulmonary tuberculosis with necessary anti-tuberculosis therapy, acquired (autoimmune) hemolytic anemia, erythrocytopenia, secondary thrombocytopenia in erythrocytes It is indicated for the symptomatic and/or prophylactic and/or therapeutic treatment of congenital hypoplastic anemia, multiple sclerosis, ulcerative colitis and regional enteritis.