Insulin solution for peroral intake
FIELD: medicine, pharmaceutics.
SUBSTANCE: the present insulin solution for peroral intake should be applied for treating patients with diabetes mellitus. The suggested insulin solution consists of water and insulin, additionally, it contains sodium chloride at the following ratio of components, weight%: insulin 0.005-0.02, sodium chloride 0.5-1.0, water - up to 100.0. The innovation provides decreased glucose level in blood of animals in case of peroral intake of the solution up to 40% at insulin dosages being about 10 U/kg animal body weight.
EFFECT: higher efficiency.
12 ex, 1 tbl
The invention relates to medicine, namely to a solution of insulin for oral administration, which is used for the treatment of patients with diabetes mellitus.
Diabetes mellitus is one of the most common serious diseases, based on an absolute or relative lack of the pancreatic hormone insulin.
Insulin (insulin from the outside) and is the only traditional method of treatment of disease (especially for patients with insulin-dependent diabetes mellitus - IDDM), allowing to compensate for the deficiency of insulin in the body. The most common method of insulin administration is subcutaneous injection. This method is inconvenient, injure the psyche of patients (especially children), causes physical and mental suffering, but most importantly, can itself exacerbate the pathology of the disease. The latter is due to the fact that after subcutaneous injection of insulin normal concentration of glucose in the blood is achieved through systematic hyperinsulinemia peripheral tissues, while the liver (the main place of activity of endogenously produced in the body, insulin) lack of insulin.
The only way to prevent complications is inevitable concomitant injection of insulin therapy is to achieve a complete simulation of the natural markrecapture hormone in vivo and to simulate the physiological difference in the level of insulin in the portal and peripheral blood circulation systems. And from this point of view, oral (through the mouth) route of insulin delivery, at which it is absorbed through the intestinal-hepatic path, the most favorable.
The main obstacle to the oral route of administration of insulin is the low stability of the hormone to the action of proteolytic enzymes of the gastrointestinal tract that leads to the destruction of insulin during its passage from the mouth to the small intestine.
In recent decades there have been many attempts to create an oral form of insulin, however, still failed to develop an effective drug that can compete on its therapeutic effect with insulin, administered by injection.
A known solution of insulin for oral administration, consisting of insulin and water [WO 96/36352, PCT/CA/00305, AND 61 R 38/28, 1996]. The solution additionally contains a substance that accelerates the absorption of insulin in the small intestine, as well as inhibitors of proteolytic enzymes of the small intestine, preventing the destruction of the insulin.
The disadvantage of this solution is the impossibility of direct use for oral administration of insulin. Since the solution does not contain compounds that prevent hydrolysis of insulin in the stomach, before orally administered solution animate CC is completed with a sodium bicarbonate solution, which neutralizes the acidic environment of the stomach. Although the physiological action of the solution is rather high (oral rat 10 units of insulin in the composition of the solution containing 0.02 wt.% insulin causes a decrease in the concentration of glucose in the blood of animals 70-80%), the need to fully neutralize the acidic environment of the stomach sodium bicarbonate before the introduction of the solution makes it completely unsuitable for practical application.
The closest in technical essence and the achieved results to the claimed solution is a solution of insulin for oral administration, consisting of insulin and water in the following ratio of components: water to 99.6 wt.%, insulin 0.4 wt.% [M.Saffran, B.Pansky, G.C.Budd, F.E.Williams, Insulin and the gastrointestinal tract, Journal of Controlled Release, 1997, V.46, p.89-98].
The disadvantage of this method is the low efficiency of insulin. When using this solution instead of drinking water, that is, when a rat hundred mg of insulin, the glucose concentration in the blood of rats is reduced by 40-60%, but a large number of concentrated solution of insulin has a negative effect on the digestive process. After introduction of the solution animals lose weight, and in their digestive tract find a large amount of undigested food.
The aim of the invention is to increase the effektivnosti of insulin action.
The solution of the set goal is achieved by the fact that the solution of insulin for oral administration, consisting of water and insulin further comprises sodium chloride is in the following ratio of components:
insulin - 0,005-0,02 wt.%,
sodium chloride is 0.5 to 1.0 wt.%,
water up to 100 wt.%.
Example 1. In the water dissolve the sodium chloride to achieve a concentration of 0.9 wt.% and insulin to achieve a concentration of 0.01 wt.%. 10 ml of the obtained solution containing 1 mg (25 units) of insulin orally administered to the rabbit. Insulin dose of 9.7 units/kg of body weight of the rabbit. Then after 30, 60, 90 and 120 minutes measure the concentration of glucose in the blood, which is taken from the ear of the rat. The results are shown in the table.
Examples 2-8. The solutions prepared in example 1. The composition of the solutions and the results of their tests are given in the table.
Examples 9-11 (control). The solutions prepared in example 1. The composition of the solutions and the results of their tests are given in the table.
Example 12 (control). Rabbit injected subcutaneously with 3 ml of insulin with a concentration of 0.02 wt.%. The insulin dose is 5 units/kg weight of the animal. The results are given in the table.
It is seen that the use of dilute solutions of insulin claimed composition reduces the level of glucose in the blood of animals by oral administration of the solution to 40% at doses of insulin 10 units/to the weight of the animal. A similar decrease in the level of glucose in the blood after subcutaneous injection of a solution of insulin is achieved at a dose of only 2 times lower (example 12K). Increasing the concentration of a solution of insulin by oral administration leads to less efficient use of insulin (examples 9K and 10K). The decrease in the concentration of a solution of insulin while maintaining the dose of insulin is impractical, as it requires the introduction of large quantities, but does not improve the efficiency of insulin. Dose reduction of insulin (example 11K) does not provide sufficient reduction of glucose by oral administration of a solution. In the prototype, the reduction of the glucose level of 40% is achieved by oral administration to animals of a solution of insulin in doses of more than 1000, which in principle is dangerous and never, apparently, will not be approved for use.
|# example||Con-tion of NaCl, wt.%||Con-tion of insulin, wt.%||The insulin dose, units/kg||The concentration of glucose in the blood of rabbits, mg/100 ml|
|12K, subcutaneous injection||0,9||0,02||5,1||97||58||51||53||60|
|*the time after injection, min|
A solution of insulin for oral administration, consisting of insulin, and water, characterized in that it further contains sodium chloride is in the following ratio, wt.%:
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to novel lactam compounds of the formula (I) or their pharmaceutically acceptable salts wherein A means phenyl, thienyl, pyridyl, pyrimidinyl, pyrazinyl; R2, R3 and R4 can be similar or different and mean independently of one another hydrogen atom (H), halogen atom, -OH, (C1-C6)-alkyl, (C1-C6)-alkoxy-group, -NH2, -NO2, -CF3, phenyl that can comprise substitute(s), benzyloxy-group that can comprise substitute(s), pnehylvinyl, and one among R2, R3 and R4 means -CF3-O- and others mean H; B means phenyl that can comprises substitute(s), monocyclic aliphatic (C3-C8)-ring, dihydropyrane ring; -X- and -Y- xan be similar or different and they mean independently -O-, -NH-, -NR5-, -S-; Z means -CH2-, -NH-; W means -NR1-, -CR8R9- wherein R1 means H; R8 and R9 are similar or different and mean H; wherein R5 represents a linear alkyl group that can comprise substitute(s), (C1-C8)-linear or branched alkoxycarbonyl group, acyl group chosen from formyl group, acyl group comprising (C1-C6)-alkyl, (C1-C6)-alkenyl or (C1-C6)-alkynyl group that can comprise substitute(s), carbamoyl group comprising (C1-C6)-alkyl group at nitrogen atom that can comprise substitutes, sulfonyl group comprising (C1-C6)-alkyl group at sulfur atom that can comprise substitute(s); each among a, b and c represents position of carbon atom under condition that: (i) substitute(s) is chosen from the group comprising halogen atom, -OH, (C1-C6)-alkyl, mercapto-group, (C1-C6)-alkoxy-group, -NO2, -COOH, -CF3, phenyl, -NH2, (C1-C8)-linear or branched alkoxycarbonyl group, (C1-C8)-linear or branched acyl group, (C1-C8)-linear or branched acyloxy-group; (ii) when B represents benzene ring, each among -X- and -Y- represents -NH-, -Z- represents -CH2- and -W- represents -NH- then R2, R3 and R4 can not mean phenyl group, 4-bromophenyl group, 4-hydroxyphenyl group, 4-methoxyphenyl group, 2-hydroxyphenyl group, 3,4-dimethoxyphenyl group or 3-methoxy-4-hydroxyphenyl group. Compounds of the formula (I) show the enhanced capacity for transport of sugar and can be used in pharmaceutical compositions for prophylaxis and/or treatment of diabetes mellitus and diabetic nephropathy.
EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.
19 cl, 21 tbl, 54 ex
FIELD: chemistry of heterocyclic organic compounds, medicine.
SUBSTANCE: invention relates to a novel heterocyclic derivative of the formula (I'): , wherein R1 represents hydrogen atom or (C1-C6)-alkyl; R2 represents-CO-C(R4)=C(R4)-R5 wherein R4 represents hydrogen atom; R5 represents (C2-C8)-alkenyl; R3 represents hydrogen atom or (C1-C4)-alkyl; X represents oxygen atom or sulfur atom; R20 represents phenyl substituted with unsubstituted (C1-C6)-alkyl, (C1-C6)-alkyl substituted with fluorine atom, (C1-C4)-alkoxy-group, phenyl-(C1-C4)-alkoxy-group, hydroxyl group, halogen atom, nitro-group, unsubstituted amino-group or amino-group substituted with (C1-C4)-alkyl; n means a whole number from 1 to 4, or to its pharmaceutically acceptable salt. Also, invention relates to heterocyclic derivative of the formula (I): , wherein R1 represents hydrogen atom or (C1-C6)-alkyl; R2 represents -CO-C(R4)=C(R4)-R5 wherein R4 represents hydrogen atom; R represents (C4-C8)-alkyl or (C2-C8)-alkenyl or -CO-C≡C-R6 wherein R6 represents (C1-C8)-alkyl; R3 represents hydrogen atom or (C1-C4)-alkyl; X represents oxygen atom or sulfur atom; n means a whole number from 1 to 4, or its pharmaceutically acceptable salt. Compounds of the formulas (I') and (I) are effective as a hypoglycemic agent, hypolipidemic agent, agent improving resistance to insulin, therapeutic agent in treatment of diabetes mellitus, therapeutic agent in treatment of diabetes mellitus complications, agents enhancing tolerance to glucose, anti-arteriosclerotic agent, agents against obesity or agent for X syndrome.
EFFECT: valuable medicinal properties of derivatives.
14 cl, 2 tbl, 56 ex
FIELD: organic chemistry, biochemistry, medicine, pharmacy.
SUBSTANCE: invention relates to novel condensed cyclopropylpyrrolidines of the formula: wherein x means 0 or 1 and y means 0 or 1 under condition that x means 1 when y means 0, and x means 0 when y means 1; and wherein n means 0 or 1; X means hydrogen atom (H) of group -CN; R1, R2, R3 and R4 are similar or different and chosen independently from H, (C1-C10)-alkyl, (C2-C12)-alkenyl, saturated (C3-C10)-cycloalkyl, saturated (C3-C10)-cycloalkyl-(C1-C10)-alkyl, saturated (C3-C10)-bicycloalkyl, saturated (C3-C10)-tricycloalkyl, hydroxyl-(C1-C10)-alkyl-saturated (C3-C10)-cycloalkyl, (C1-C10)-alkylthio-(C1-C10)-alkyl, (C6-C10)-aryl-(C1-C10)-alkylthio-(C1-C10)-alkyl, (C6-C10)-aryl-(C1-C10)-alkyl, 5- or 6-membered heteroaryl comprising one nitrogen atom (N) or one oxygen atom (O), 5- or 6-membered heteroaryl comprising one atom N condensed with (C6-C10)-aryl ring, 5- or 6-membered heteroaryl comprising one atom N or one atom O, (C1-C10)-alkyl, cycloheteroalkyl that represents (C5-C8)-saturated ring comprising one heteroatom, such as N or O; if necessary, all compounds comprise 1, 2, 3, 4 or 5 groups of substitutes at corresponding carbon atom chosen from halogen atom, (C1-C10)-alkyl, (C2-C12)-alkenyl, hydroxy-group, hydroxy-(C1-C10)-alkyl or cyano-group; R1 and R4 can form in common, if necessary, the group -(CR5R6)m- wherein m means 2-6, and R5 and R6 are similar or different and chosen independently from hydroxy-group, H or (C1-C10)-alkyl including all their stereoisomers; and their pharmaceutically acceptable salt, or prodrug esters and all their stereoisomers. These compound inhibit activity of dipeptidyl peptidase IV that allows their using in pharmaceutical compositions used in treatment of diabetes mellitus of type-2.
EFFECT: valuable medicinal properties of compounds.
20 cl, 6 tbl, 113 ex
FIELD: medicine, pharmaceuticals, in particular compositions for treatment of insulin-independent II type diabetus mellitus.
SUBSTANCE: claimed composition represents single solid dosed pharmaceutical for oral administration and contains effective dose of metformin and glibenclamide, wherein said glibenclamide contains powdery particles with specific surface of 1.7-2.2 m2/g. Also disclosed are method for treatment of insulin-independent diabetes or hyperglycemia; method for providing and enhancing of glibenclamide bioavailability in human body (variants).
EFFECT: composition with increased glibenclamide bioavailability.
68 cl, 3 ex, 7 tbl, 3 dwg
FIELD: organic chemistry.
SUBSTANCE: invention relates to new polymorphous crystalline forms of 5-[4-[2-[N-methyl-N-(2-pyridyl)-amino]-ethoxy]-benzyl]-thiazolidine-2,4-dione maleate of formula and stereomers thereof.
EFFECT: polymorphous crystalline forms of high stability.
12 cl, 1 tbl, 13 dwg, 5 ex
FIELD: medicine, in particular methods (variants) for prophylaxis and treatment of disorders associated with abnormal lipid carbohydrate metabolism or circulatory disturbances associated therewith in mammalian.
SUBSTANCE: claimed methods includes administration of pioglytazone or pharmaceutically acceptable salt thereof in combination with at least one member selected from group containing alpha-glucosidase inhibitor, aldose reductase inhibitor, biguanide, statin derivative, squalene, fibrate compound, enhancer of low density lipoprotein catabolism and inhibitor of angiotensine converting enzyme to mammalian. Alternatively method includes administration of pioglytazone or pharmaceutically acceptable salt thereof in combination with enhancer of insulin secretion and/or insulin preparation.
EFFECT: synergic effect in relation to lowering of glucose levels in blood, body mass losses, with decreased amount of side effects.
13 cl, 8 tbl
SUBSTANCE: the present innovation deals with obtaining preparations for treating diabetes mellitus based upon medicinal plants. The suggested antidiabetic species contains the folds of kidney beans fruits, goat's rue grass (Galega officinalis), Leonorus grass, leaves of common nettle and leaves of green tea at equal ratios. The suggested innovation could be presented as phyto-tea in filter-packs per 2.0 g. At applying the present species blood level of sugar is decreased, and in case of light form of diabetes mellitus - it is normalized that enables to decrease the dosages of antidiabetic preparations.
EFFECT: higher efficiency of application.
2 ex, 2 tbl
FIELD: medicine, pharmacy.
SUBSTANCE: invention proposes a hydrophilic pharmaceutical composition with hypoglycemic effect comprising nateglinide crystals of B-type as an active component. The composition has edge angle to water surface 111 degrees or less. This edge angle is created by addition at least one hydrophilic substance to the composition chosen from groups comprising of hydrophilic polymers, surfactants, sugars and sugar-alcohols. Invention provides easy method for preparing the composition, its high solubility and rather rapid release of nateglinide.
EFFECT: improved and valuable properties of pharmaceutical composition.
13 cl, 8 dwg, 4 tbl, 6 ex
FIELD: medicine, endocrinology.
SUBSTANCE: invention proposes a medicinal agent for reducing the blood sugar content after food intake and representing a compound included in meglytinides and, if necessary, a pharmaceutically acceptable carrier. Nateglynide is the preferable compound. The complication associated with diabetes mellitus is chosen among nephropathy, retinopathy, neuropathy and angiopathy. At least one agent chosen among antihypertensive agent, vasodilating agent and antihyperlipidemic agent can be used with agent used simultaneously for reducing the blood content after food intake. Invention provides realization of indicated prescription.
EFFECT: valuable medicinal properties of drugs.
15 cl, 2 dwg, 5 ex
FIELD: organic chemistry, medicine, endocrinology.
SUBSTANCE: invention relates to improved methods for modulation of diabetes mellitus type II in mammal and modulation of resistance to insulin. Methods involve administration to indicated mammal needing in this treatment of (-)-stereoisomer of compound of the formula (I): wherein R is chosen from group including hydroxy-, lower araloxy-, d-(lower)-alkylamino-(lower)-alkoxy-, (lower)-alkylamido-(lower)-alkoxy-, benzamido-(lower)-alkoxy-, ureido-(lower)-alkoxy-, N'-(lower)-alkyl-ureido-(lower)-alkoxy-, carbamoyl-(lower)-alkoxy-, halophenoxy-substituted lower alkoxy-, carbamoyl-substituted phenoxy-group; or R represents hydrolysable ester group; each X represents independently halogen atom; or its pharmaceutically acceptable salt wherein (-)-stereoisomer doesn't comprise conceptually (+)-stereoisomer. Also, invention relates to pharmaceutical compositions comprising (-)-stereoisomer of compound of the formula (I) and wherein compositions show significantly reduced inhibitory effect on activity of cytochrome P-450 2C9 as compared with racemic composition having 0% enantiomeric excess of (-)-stereoisomer.
EFFECT: valuable medicinal properties of compound and pharmaceutical composition, improved preparing methods.
59 cl, 21 dwg, 8 tbl, 18 ex
SUBSTANCE: the present innovation deals with the technique to prepare 10%-calcium gluconate solution for injections including dissolving the substance, filtration, pouring and sterilizing; moreover, the substance should be pre-mixed at about 10-30° C with aqueous solution of hydrogen peroxide at concentration ranged 0.00015-0.15% to be kept for about 4-24 h; the mixture should be dissolved in water at 70-90° C to be heated up to 100 C, not more and kept at pressure (0.5±0.02) MPa for 20 min, not less, then solution should be poured into the ampoules and sterilized with flowing steam at 100 C, not more for 1 h, not more. The innovation enables to obtain a stable and noncaramelizing and noncrystalizing solution of calcium gluconate.
EFFECT: higher efficiency.
3 ex, 3 tbl
SUBSTANCE: the present innovation deals with new compositions in the form of a single-stage gel that contains minoxidyl, a thickening agent and a pharmaceutically acceptable solvent. The composition contains 3-8 weight% minoxidyl. Noncarbometric thickening agent is not a heterobiopolysaccharide or cellulose derivative. Carbometric thickening agent being tolerant to a solvent is not a carbometer of Carbopol 934P type. Minoxidyl is practically solubilized in the composition. It is, also, described the method for preparing minoxidyl-containing composition. Also, the present innovation deals with the ways of treating or preventing alopecia in patients, moreover, these methods deal with local application of these compositions at the site of alopecia according to the innovation suggested. Thus, it is possible to obtain a single-phase composition by its consistence of moderate viscosity that could be obtained upon conventionally applied equipment.
EFFECT: higher efficiency of application.
83 cl, 8 ex
FIELD: pharmaceutical industry.
SUBSTANCE: invention relates to aqueous autoclaving composition for parantheral administration useful in treatment of pathological heart conditions. Claimed composition contains methyl-3-[4-(2-hydroxy-3-isopropylamino)propoxy]-phenylpropionate hydrochloride (esmolol hydrochloride), buffer agent and osmotic controlling agent. Composition has pH between 4.5 and 5.5. Also disclosed is method for production of abovementioned esmolol hydrochloride composition including step of composition autoclaving in sealed container for time sufficient to sterilize the composition. After autoclaving composition is stable for at least 24 months.
EFFECT: composition of prolonged storage time.
11 cl, 3 ex
FIELD: pharmaceutical industry, in particular cyprofloxacine solution.
SUBSTANCE: claimed solution contains cyprofloxacine hydrochloride, sodium salt of ethylenediamine-N,N,N1,N1-tetraacetic acid, α-hydroxypropionic acid, sodium chloride, water for injections.
EFFECT: drug of increased biological availability without side effects.
FIELD: pharmaceuticals, in particular topical drugs for treatment of skin and mucous membrane disorders.
SUBSTANCE: invention relates to metronidazole aqueous solution for production of pharmaceutical composition having physical stability for at least one week at 5°C and metronidazole concentration of 0.75 %. Said solution contains combination of agents enhancing solubility, wherein one agent represents cyclodextrin, such as beta-cyclodextrin, and another one represents compound differ from cyclodextrin. Methods of production and therapeutic application of abovementioned solutions also are described.
EFFECT: physically stable metronidazole aqueous solutions containing minimized amount of cyclodextrins.
48 cl, 6 tbl, 5 ex
FIELD: medicine, in particular ophthalmology.
SUBSTANCE: claimed composition contains antibiotic or mixture thereof, carnozine, topical anesthetic of shortcut action or mixture thereof, topical anesthetic of prolonged action or mixture thereof, steroidal anti-inflammatory agent and viscoelastic in specific component ratio (mass %).
EFFECT: decreased number of infective complications after surgical operations, accelerated rehabilitation period.
SUBSTANCE: solution has extract produced from cattle prostate and a carbohydrate.
EFFECT: no toxic effects; storage stability.
2 cl, 1 tbl
FIELD: pharmaceutical industry, in particular phospholipid-based pharmaceutical composition hawing hepatoprotective and metabolism normalizing activity in form of tablets, pellets, capsules, injection solutions, etc.
SUBSTANCE: claimed composition contains both plant and animal origin phospholipid, essential amino acid such as methionine and threonine, and filler at total phospholipid and amino acid content of 15-80 % in mass ratio of 2:1.
EFFECT: effective pharmaceutical composition having excellent hepatoprotective and lipid, protein, and carbohydrate metabolism normalizing activity.
12 cl, 26 tbl, 98 ex
SUBSTANCE: method involves acidifying and/or alkalinized by buffering and/or controlling pH to provide nicotine tmax in arterial subject blood in short time after introduction. Aerosol atomizing is preferentially done into oral cavity for following distribution in lungs. Method for preparing the composition, system for achieving smoking desire reduction and/or satisfaction feeling without smoking is also suggested.
EFFECT: enhanced effectiveness in introducing nicotine via lungs; avoided harmful actions caused by smoking.
FIELD: medicine; medical engineering.
SUBSTANCE: preparation comprises carrier treated with electromagnetic field. The carrier is a substance selected from a group composed of pharmaceutically permissible powder or pill substrate having crystalline substance in the amount of at least 23% by mass, physiologic fluid or liquid crystals. The carrier is treated with electromagnetic field using frequencies of 0.01-9.0 kHz, 10.0-100.0 kHz or 0.5-10.0 MHz during 0.5-60 min. Method involves producing a preparation comprising carrier being a substance selected from a group composed of pharmaceutically permissible powder or pill substrate having crystalline substance in the amount of at least 23% by mass, physiologic fluid or liquid crystals. The carrier is treated with electromagnetic field of abovementioned frequency during 0.5-60 min. Optimum treatment time is selected depending on carrier nature.
EFFECT: stable properties during one year; enhanced effectiveness in agricultural production processes; encouraging future application in medicine.
13 cl, 2 tbl
SUBSTANCE: a solid pharmaceutical composition contains therapeutically efficient quantity of peptide as a pharmacological active substance, crospovidone or povidone, and an agent that favors peptide's introduction. A peptide is being calcitonin, salmon's calcitonin preferably. The above-mentioned agent is being 5-CNAC (N-(5-chlorsalicyloyl)-8-aminocaprylic acid), preferably, disodium salt 5-CNAC. The composition suggested provides high biological availability of peptides, such, for example, as calcitonin.
EFFECT: higher efficiency of application.
9 cl, 5 ex, 4 tbl