A method for the treatment of pituitary adenomas
(57) Abstract:The invention relates to medicine and can be used in the treatment of pituitary adenomas. The method includes remote gamma-therapy, medical therapy with dopamine agonists and measurement of prolactin in the blood PR1 to conduct remote gamma-therapy and AC2 after conducting remote gamma-therapy, when values of PR1 is less than 1000 MCAD/l prescribed oral administration of the dopamine agonist 6 months after completion of remote gamma-therapy at 5.0 mg only once in the second half of the day for 18 months, when the value of R1 in the range of 1,000-2,000 MCAD/l prescribed for administration of dopamine agonist at 5.0 mg per day since remote gamma-therapy and within 2-3 years after its completion, and when PR1 more than 2000 MCAD/l designate the reception of a dopamine agonist on 5.0-7.5 mg two or three times a day until the start of the remote gamma-therapy and until the normalization of AC2. The method allows to define clearly the time of reception of dopamine agonist, depending on its initial indicator that allows you to improve the comfort of the patient's life, to exclude the risk of complications unreasonably high doses of the drug and reduce likely retina relates to medicine and can be used in the treatment and observation of patients, which as the primary treatment was applied remote gamma-therapy.There are several directions in the treatment of pituitary adenomas associated with hyperprolactinemia or without it, some of which recommend the use of as a method of treatment or medicamental method, or remote gamma-therapy (Archer DF of Current concepts and treatment of hyperprolatinemia" Obst. Gynecol. Clin. N. A. - 1987, v. l4, N 4, p. 979-998).The disadvantages of these methods include the use of each of them independently, which does not allow you to individually adjust the treatment of pituitary adenomas, and consequently to predict the effectiveness of treatment.Closest to the present invention is a method for the treatment of pituitary adenomas, including remote gamma-therapy, medical therapy with dopamine agonists (A. Grosman et. al. Treatment of prolactinomas with megavoltage radioterapy. - Br. Med. J., 1984, v. 288, 6424 N, p. 1105-1109). The dopamine agonist appointed, either simultaneously with radiation therapy, or after its completion for a minimum of five years or more. This produces periodic cancellation of a dopamine agonist to clarify the degree of reduction of the level of prolactin in the blood.Disadvantages of the proposed method of yavlyayushimisya the level of prolactin in the blood before remote gamma-therapy and the date of the meeting.The problem posed by the authors, is to remedy these disadvantages by improving the efficiency of the control of the concentration of prolactin in the blood within the established empirically terms depending on its initial level. Reception of dopamine agonist helps maintain normal levels of prolactin in the blood until the disappearance of the causes of hyperprolactinemia due to a remote gamma-therapy.For this purpose, the method of treatment of pituitary adenomas, including remote gamma-therapy, medical therapy with dopamine agonists, proposed to measure the content of prolactin in the blood PR1 to conduct remote gamma-therapy and after the remote gamma-therapy AC2, and when values of PR1 is less than 1000 MCAD/l to assign oral administration of the dopamine agonist 6 months after completion of distance gamma-therapy at 5.0 mg only once in the second half of the day for 18 months, when the value of R1 in the range of 1,000-2,000 MCAD/l to assign the reception of dopamine agonist at 5.0 mg per day since remote gamma-therapy, and within 2-3 years after its completion, and when PR1 more than 2000 MCAD/l to assign the reception of a dopamine agonist on 5.0-7.5 mg two or three times a day since the course is IEMA of dopamine agonist, depending on its initial index, allows you to improve the comfort of life of the patient, to reduce the material cost of treatment, to exclude the risk of complications unreasonably high doses of the recommended drug and reduce the risk of hormone homeostasis when reducing the specified dosage.The method is as follows.The patient with suspected pituitary adenoma is an x-ray region of the Turkish saddle. When you confirm the diagnosis and determine the content of prolactin in the blood and subsequently used as the main criterion affecting the scheme oral administration of dopamine agonists.If the initial level of PR1 prolactin does not exceed 1000 MCAD/l, the first is the rate of remote gamma-therapy with two or three fields in the standard mode, dose fractionation to a total dose of 60 Gy. 6 months after completion of treatment just before a sharp increase in the concentration of prolactin in the blood, caused by radiation damage to the blood vessels gipotalyamo-pituitary region, prescribe oral administration of the dopamine agonist (parlodel) at a dose of 5.0 mg daily during the second half of the day during the 18 months which comes back the development of damage to vessels, caught in the radiation zone, and the content of prolactin NP2 in the blood is returned to the original level.If the initial level of PR1 prolactin from 1000 to 2000 MCAD/l, there will be a slow but steady decline in the blood to normal after AC2 remote gamma-therapy, as shown by numerous studies, 2-3 years after treatment. To normalize hormonal imbalance due to its high content of prolactin in the blood, during the whole course of remote gamma-therapy since its beginning and in anticipation of the implementation of therapeutic potential treatment within 2-3 years after its completion prescribed for administration of dopamine agonist at 5 mg orally in the afternoon. Cancellation it is not produced during the above period.In patients with baseline levels of prolactin PR1 not above 1500 MCAD/l, cancel parlodel only 3 years after the end of treatment will not lead to recurrence of hyperprolactinemia, while rejecting parlodel possible only after 3 years after remote gamma-therapy in those levels of prolactin in the blood have more than 1500 and less than 2000 MCAD/L.If the original content of prolactin PR1 in the shelter of the Les graduation is only possible by assigning a higher dose of parlodel, take two or three doses per day. As a rule, the daily dose of parlodel in this case is 7,56 10 mg, administered since remote gamma-therapy and continues after at least 5 years. Determination of the level of prolactin in patients receiving parlodel optional and can only be performed to confirm the adequacy of the treatment. After this period it is recommended that control the abolition of the dopamine agonist to establish the degree of reduction of prolactin NP2 in the blood, caused by irradiation. If control study level of prolactin in the blood reveals its high content parlodel appointed again to the same dose.Example 1.Patient P. , 1940, R., x-ray examination revealed a pituitary adenoma. The study of hormones in the blood showed the presence of prolactin in the blood level PR1=500 MCAD/L. patients received a course of distance gamma-therapy up to 60 Gy. - Control study level of this indicator within 5 months after completion of treatment showed only minor fluctuations. After 6 months a marked increase in the content of prolactin in the blood. The tendency to increase in the blood of this index had months of the initial level by 50%. Further, the content of prolactin in the blood slowly began to decline and did not differ from baseline through 24 months after completion of treatment.Thus, the absence of the treatment program the purpose of the dopamine agonist resulted in permanent hyperprolactinemia resulting in hormonal homeostasis in the body.Example 2.Patient M., 1945 R., was admitted with a diagnosis of acromegaly, initial level of prolactin in the blood was PR1=675 MCAD/HP course was held remote gamma-therapy about pituitary adenomas, and 6 months after its completion scheduled parlodel one time oral dose of 5 mg in the second half of the day for 18 months. After 24 months after the end remote gamma-therapy receiving parlodel was discontinued. Control study of the content of prolactin NP2 blood conducted in this patient every three months, showed no deviation values of this index from its initial level.Example 3.Patient K., 1949 R., enrolled in the radiology Department with the diagnosis of pituitary adenoma. In the study of hormones in the blood revealed high concentrations of prolactin level PR1=1360 MCAD/L. Since the DHT Bosnia exposure normalization of prolactin levels AC2. The patient continued taking parlodel in the same dose after irradiation for 2 years, after which parlodel was cancelled. Further monitoring of this indicator during the 5 years allowed us to verify that it is stable and does not differ from the norm.Example 4.Patient C., 1941, p., a course of radiotherapy to 60 Gy over prolactinoma pituitary. Before treatment PR1=3245 MCAD/L. Since the beginning of the irradiation, the patient received oral parlodel 5 mg 3 times a day. Receiving parlodel on the above scheme was continued after completion of DHT. 6 months after completion of treatment, while parlodel, identified the prolactin blood AC2 to confirm the adequacy of treatment by parlodelum. Over the next 4.5 years, the patient continued to take parlodel as previously described. Removal of the drug and determine the degree of reduction of prolactin in the blood after DHT conducted 5 years after its completion. As indicated a significant decline in blood, but he remained above normal, the patient was recommended to continue taking parlodel dose, half what it was initially assigned. Normalization of prolactin levels in the blood fixed aemy method allows you to control the number of patients which the treatment of DHT on adenoma of the pituitary gland, hormonal imbalance, available at the beginning of treatment or arising after its completion, which in turn increases the comfort of the life of this category of patients. A method for the treatment of pituitary adenomas, including remote gamma-therapy, medical therapy with dopamine agonists, characterized in that it further measure the content prolactin blood PR1 to conduct remote gamma-therapy and after the remote gamma-therapy AC2, when values of PR1 is less than 1000 MCAD/l prescribed oral administration of agonito dopamine after 6 months. after completion of remote gamma-therapy for 18 months. at 5.0 mg once in the afternoon, when the value of R1 in the range of 1000 - 2000 MCAD/l appoint a dopamine agonist at 5.0 mg per day since remote gamma-therapy and for 2 to 3 years after its completion, when PR1 more than 2000 MCAD/l designate the reception of a dopamine agonist on 5.0 - 7.5 mg two or three times a day since the beginning of the remote gamma-therapy and until the normalization of AC2.
FIELD: medicine, pharmacology, pharmacy, medicinal biochemistry.
SUBSTANCE: invention proposes a pharmaceutical composition that comprises, in particular, N-(1-octyl-5-carboxymethyl-dimethylindolin-7-yl)-2,2-dimethylpropaneamid or its pharmacologically acceptable salts as inhibitor of enzyme ACAT and inhibitor of HMG-CoA-reductase that represents pravastatin, lovastatin, simvaststin, fluvastatin, rivastatin, atorvastatin, rosuvastatin or pitavastatin used as active component of the composition. The combination of active substances shows the expressed synergistic effect. Invention provides enhancing activity of the composition in clinical applying.
EFFECT: valuable medicinal properties of composition.
71 cl, 2 tbl, 3 ex
FIELD: organic chemistry, pharmaceutical composition.
SUBSTANCE: new isoindoline-1-on-glucokinase activators of general formula I , as well as pharmaceutically acceptable salts or N-oxide thereof are disclosed. In formula A is phenyl optionally substituted with one or two halogen or one (law alkyl)sulfonyl group, or nitro group; R1 is C3-C9cycloalkyl; R2 is optionally monosubstituted five- or six-membered heterocyclic ring bonded via carbon atom in cycle to amino group, wherein five- or six-membered heteroaromatic ring contains one or two heteroatoms selected form sulfur, oxygen or nitrogen, one of which is nitrogen atom adjacent to carbon atom bonded to said amino group; said cycle is monocyclic or condensed with phenyl via two carbon atoms in cycle; said monosubstituted with halogen or law alkyl heteroaromatic ring has monosubstituted carbon atom in cycle which in not adjacent to carbon atom bonded to amino group; * is asymmetric carbon atom. Claimed compounds have glucokinase inhibitor activity and useful in pharmaceutical composition for treatment of type II diabetes.
EFFECT: new isoindoline-1-on-glucokinase activators useful in treatment of type II diabetes.
23 cl, 3 dwg, 43 ex
FIELD: drugs, medicine.
SUBSTANCE: invention relates to application of 1-methylindolyl-3-thioacetic acid tris-(2-hydroxyethyl)ammonia salt, which is known hypolipidemic agent, as immunosuppressor. Present invention ales it possible to produce pharmaceuticals for transplanted organ and tissue rejection prophylaxis or treatment of various immune-associated diseases.
EFFECT: new drug for transplant rejection prophylaxis or treatment of immune-associated diseases.
3 tbl, 3 ex
FIELD: organic chemistry, medicine, pharmaceutical chemistry.
SUBSTANCE: invention relates to new compound - 1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethylaminomethyl-5-hydroxy-6-bromoindole mesylate and its hydrates. Indicated mesylate salt exceeds other 1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethylaminomethyl-5-hydroxy-6-bromoindole salts by its antiviral activity and can be used in different medicinal formulations. Invention expands assortment of agents used for treatment of viral infection. New antiviral agent shows high effectiveness treatment and low toxicity.
EFFECT: enhanced and valuable medicinal properties of agent and composition.
3 cl, 6 tbl, 9 ex
FIELD: organic chemistry, biochemistry.
SUBSTANCE: invention relates to new substituted indoles of the formula (I): and/or stereoisometic form of compound of the formula (I) and/or physiologically acceptable salt of compound of the formula (I) wherein R3 means residue of the formula (II): wherein D means -C(O)-; R7 means hydrogen atom (H) or -(C1-C4)-alkyl; R8 means (a) typical residue of amino acid among the group: phenylalanine or homophenylalanine wherein phenyl residue is unsubstituted or substituted with halogen atom; or (b) -(C1-C4)-alkyl wherein alkyl is a linear or branched and (b) 1) mono- or multi-substituted independently of one another with pyrrole residue wherein this residue is unsubstituted or substituted with halogen atom; (b) 2) mono- or bi-substituted independently with residue -S(O)x-R10 wherein x = 0, 1 or 2, or (b) 3) mono- or bi-substituted independently of one another -N(R10)2 wherein R10 means (a) hydrogen atom (H); (b) means -(C1-C6)-alkyl wherein alkyl is unsubstituted or substituted with halogen atom from 1 to 3 times; (c) phenyl wherein phenyl is substituted or substituted with halogen atom from 1 to 3 times; in the case (R10)2 residues R10 have values independently of one another (a), (b), (c); Z means (a) residue of heterocycles group comprising benzothiadizine, pyrrole, pyridine, pyrimidine, pyrazine, imidazole, pyrazole, oxazole, isoxazole, thiazole, isothiazole, tetrazole, oxadiazolone, triazole being heterocycles are unsubstituted or substituted with -NH2=, =O, alkoxycarbonyl or aminocarbonyl from 1 to 3 times, or (b) means -C(O)-R11 wherein R11 means 1. -O-R10 or 2. -N(R10)2; R9 means (a) hydrogen atom (H); (b) means (C1-C6)-alkyl wherein alkyl is unbranched or branched and substituted with phenyl or =O independently of one another from 1 to 3 times; (c) phenyl wherein phenyl is unsubstituted or substituted with halogen atom; R1, R2 and R4 mean hydrogen atom (H); R5 means hydrogen atom (H); R6 means (a) phenyl wherein phenyl is unsubstituted or substituted with -NH2; (b) pyridine, or (c) pyrimidine being pyridine or pyrimidine is unsubstituted or substituted with groups -NH2, -NH-CH3. Compounds of the formula (I) are specific inhibitors of IkB kinase.
EFFECT: valuable biochemical properties of compounds.
3 cl, 3 tbl, 29 ex