213 results about "Basal bolus" patented technology

Conjugate compounds of formula (A):wherein:R2 iswhere R36a and R36b are independently selected from H, F, C1-4 saturated alkyl, C2-3 alkenyl, which alkyl and alkenyl groups are optionally substituted by a group selected from C1-4 alkyl amido and C1-4 alkyl ester or, when one of R36a and R36b is H, the other is selected from nitrile and a C1-4 alkyl ester;R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR′, NO2, Me3Sn and halo;R7 is independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR′, NO2, Me3Sn and halo;Y is selected from formulae A1, A2, A3, A4, A5 and A6:L is a linker connected to a cell binding agent;CBA is the cell binding agent;n is an integer selected in the range of 0 to 48;RA4 is a C1-6 alkylene group;either(a) R10 is H, and R11 is OH, ORA, where RA is C1-4 alkyl; or(b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or(c) R10 is H and R11 is OSOzM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation;R and R′ are each independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups, and optionally in relation to the group NRR′, R and R′ together with the nitrogen atom to which they are attached form an optionally substituted 4-, 5-, 6- or 7-membered heterocyclic ring;wherein R16, R17, R19, R20, R21 and R22 are as defined for R6, R7, R9, R10, R11 and R2 respectively;wherein Z is CH or N;wherein T and T′ are independently selected from a single bond or a C1-9 alkylene, which chain may be interrupted by one or more heteroatoms e.g. O, S, N(H), NMe, provided that the number of atoms in the shortest chain of atoms between X and X′ is 3 to 12 atoms; andX and X′ are independently selected from O, S and N(H).

Compounds which are 1-(2'-aminoacyl)-2-cyanopyrrolidine derivatives according to general formula (1) are DP-IV inhibitors for treatment of impaired glucose tolerance or type 2 diabetes; wherein A is selected from groups (2,3 and 4); X is selected from aminoacyl groups corresponding to the natural amino acids, acyl groups R3CO, groups R4COOC(R5)(R6)OCO, methoxycarbonyl, ethoxycarbonyl and benzyloxycarbonyl; R1 is selected from H, C1-C6 alkyl residues, (CH2)aNHW1, (CH2)bCOW2, (CH2)cOW3, CH(Me)OW4, (CH2)d-C6H4-W5 and (CH2)eSW6, where a is 2-5, b is 1-4, c is 1-2, d is 1-2, e is 1-3, W1 is COW6, CO2W6 or SO2W6, W2 is OH, NH2, OW6 or NHW6, W3 is H or W6, W4 is H or W6, W5 is H, OH or OMe, and W6 is C1-C6 alkyl, optionally substituted phenyl, optionally substituted heteroaryl or benzyl and R2 is selected from H and (CH2)n-C5H3N-Y, where n is 2-4 and Y is H, F, Cl, NO2 or CN, or R1 and R2 together are -(CH2)p-where p is 3 or 4; R3 is selected from H, C1-C6 alkyl and phenyl; R4 is selected from H, C1-C6 alkyl, benzyl and optionally substitued phenyl; R5 and R6 are each independently selected from H and C<highlight>

A 5-membered heteroaromatic ring compound represented by the formula [I]wherein V is CH or N; W is S or O; R1 and R2 are each H etc.; X is —N(R4)—, —O—, —S—, —SO2—N(R5)—, —CO—N(R7)— etc.; L is wherein R20, R21, R22 and R25 are each H etc.; E is aryl or heteroaromatic ring group; R is —COOH etc.; B is aryl etc.; R3 is H etc.; Y is —C(R13)(R14)—N(R12)—C(R13)(R14)—O—, —N(R11)—, —O— etc.; A is alkylene; and Z is aryl etc., a prodrug thereof and a pharmaceutically acceptable salt thereof. The compound [I] has a superior protein tyrosine phosphatase 1B inhibitory activity and is useful as a therapeutic agent for diabetes, diabetic complications, hyperlipidemia, obesity and the like.

An automated method and system of diabetes control. The method includes establishing a blood glucose target for an insulin user, measuring an existing blood glucose level for the insulin user, and inputting the existing blood glucose level into a computer processor formed to execute an algorithm designed to calculate a corrective amount of insulin to be administered intravenously in an integrated basal-bolus manner to the insulin user if the existing blood glucose level exceeds the blood glucose target. The algorithm is based on a plurality of factors that contribute to a non-linear glucose response. The method further includes automatically delivering the corrective amount of insulin to the insulin user, and further repeating the measuring, inputting, and delivering steps one or more times to maintain the insulin user within the blood glucose target range.

The present invention provides novel carboxylic acid derivatives useful as an insulin sensitizer, a salt thereof or a hydrate of them, and a medicament comprising the derivative as the active ingredient. Specifically, it provides a carboxylic acid derivative represented by the following formula: (wherein L represents a single bond, or a C1 to C6 alkylene group, a C2 to C6 alkenylene group or a C2 to C6 alkynylene group, each of which may have one or more substituent groups; M represents a single bond, or a C1 to C6 alkylene group, a C2 to C6 alkenylene group or a C2 to C6 alkynylene group, each of which may have one or more substituent groups; T represents a single bond, or a C1 to C3 alkylene group, a C2 to C3 alkenylene group or a C2 to C3 alkynylene group, each of which may have one or more substituent groups; W represents a carboxyl group; X represents a single bond, an oxygen atom, or a group represented by the various substituent groups including -NR<X1>CQ<1>O- (wherein Q<1 >represents an oxygen atom or a sulfur atom; R<X1 >represents a hydrogen atom, a cyano group, a formyl group, or various groups including a C1 to C6 alkyl group and a C1 to C6 hydroxyalkyl group, each of which may have one or more substituent groups), ONR<X1>CQ<1>-, -NR<X1>CQ<1>-, -CQ<1>NR<X1>-, -NR<X1a>CQ<1>NR<X1b>-, -Q<2>SO2- and -SO2Q<2>-; Y represents a 5 to 14-membered aromatic group which may have one or more substituent groups and one or more hetero atoms, or a C3 to C7 alicyclic hydrocarbon group; and the rings Z and U may be the same as or different from each other and each represents a 5 to 14-membered aromatic group which may have 1 to 4 substituent groups and one or more hetero atoms, and the ring may be partially saturated.), a salt thereof, an ester thereof or a hydrate of them.

The present invention pertains to certain imidazo[4,5-b]pyridin-2-one and oxazolo[4,5 b]pyridin-2-one compounds and analogs thereof, which, inter alia, inhibit RAF (e.g., B RAF) activity, inhibit cell proliferation, treat cancer, etc., and more particularly to compounds of the formulae: wherein: J is independently —O— or —NRN1−; RN1, if present, is independently —H or a substituent; RN2 is independently —H or a substituent; Y is independently —CH═ or —N═; Q is independently —(CH2)j-M-(CH2)k— wherein: j is independently 0, 1 or 2; k is independently 0, 1, or 2; j+k is 0, 1, or 2; M is independently O—, —S—, —NH—, —NMe-, or —CH2—; each of RP1, RP2, RP5, and RP4 is independently —H or a substituent; and additionally RP1 and RP2 taken together may be CH═CH—CH═CH—; and additionally RP1 and RP5 taken together may be CH═CH—CH═CH—; L is independently: a linker group formed by a chain of 2, 3, or 4 linker moieties; each linker moiety is independently CH2—, —NRN—, —C(═X)—, or —S(═O)2—; either: exactly one linker moiety is —NRN—, or: exactly two linker moieties are —NRN—; either: exactly one linker moiety is —C(═X)—, and no linker moiety is —S(═O)2—, or: exactly one linker moiety is —S(═O)2—, and no linker moiety is —C(═X)—; no two adjacent linker moieties are —NRN—; X is independently ═O or ═S; each RN is independently —H or a substituent; A is independently: C6-14carboaryl, C5-14heteroaryl, C3-12carbocyclic, C3-12heterocyclic; and is independently unsubstituted or substituted; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, N-oxides, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit RAF (e.g., B-RAF) activity, to inhibit receptor tyrosine kinase (RTK) activity, to inhibit cell proliferation, and in the treatment of diseases and conditions that are ameliorated by the inhibition of RAF, RTK, etc., proliferative conditions such as cancer (e.g., colorectal cancer, melanoma), etc.

The present invention provides fused heterocyclic derivatives represented by the following general formula (I) or pharmaceutically acceptable salts thereof, or prodrugs thereof, which exhibit an inhibitory activity in human SGLT and are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, postprandial hyperglycemia, impaired glucose tolerance, diabetic complications or obesity, in the formula R1 to R4 represent H, OH, an amino group, etc.; R5 and R6 represent H, OH, a halogen atom, an option ally substituted alkyl group, etc.; Q represents alkylene, alkenylene, etc.; ring A represents an aryl group or a heteroaryl group; the following ring (R1) represents a group represented by the following ring (R2); G represents a group represented by the following general formula (G-1) or (G-2) (E1 represents H, F or OH; and E represents H, F, a methyl group, etc.), and pharmaceutical compositions comprising the same, and pharmaceutical uses thereof.

The present invention relates to compounds of general formula I,wherein the groups (Het)Ar and R1 are defined as in claim 1, which have valuable pharmacological properties, in particular bind to the GPR40 receptor and modulate its activity. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular diabetes type 2.

The present invention provides a novel carboxylic acid compound, a salt thereof or a hydrate of them useful as an insulin sensitizer, and a medicament comprising the compound as an active ingredient. That is, the present invention provides a carboxylic acid compound represented by the following formula, a salt thereof, an ester thereof or a hydrate of them. Wherein R<1 >represents a hydrogen atom, hydroxyl group, halogen, carboxyl group, or a C1-6 alkyl group etc., each of which may have one or more substituents; L represents a single bond, or a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group, each of which may have one or more substituents; M represents a single bond, or a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group, each of which may have one or more substituents; T represents a single bond, or a C1-3 alkylene group, a C2-3 alkenylene group or a C2-3 alkynylene group, each of which may have one or more substituents; W represents a carboxyl group; represents a single bond etc.; X represents a single bond, oxygen atom, a group represented by -NR<X1>CQ<1>O- (wherein Q<1 >represents an oxygen atom or sulfur atom; and R<X1 >represents a hydrogen atom, formyl group, or a C1-6 alkyl group etc., each of which may have one or more substituents), -OCQ<1>NR<X1>- (wherein Q<1 >and R<X1 >are as defined above), -CQ<1>NR<X1>O- (wherein Q<1 >and R<X1 >are as defined above), ONR<X1>CQ<1>- (wherein Q<1 >and R<X1 >are as defined above), -Q<2>SO2- (wherein Q<2 >is an oxygen atom or -NR<X10>- (wherein R<X10 >represents a hydrogen atom, formyl group, or a C1-6 alkyl group etc., each of which may have one or more substituents)) or -SO2Q<2>- (wherein Q<2 >is as defined above), (wherein, provided that R<X2 >and R<X3>, and / or R<X4 >and R<X5 >may together form a ring, Q<3 >and Q<4 >are the same as or different from each other and each represents an oxygen atom, (O)S(O) or NR<X10 >< /

Agents useful for the treatment of various metabolic disorders, such as insulin resistance syndrome, diabetes, hyper-lipidemia, fatty liver disease, cachexia, obesity, atherosclerosis and arteriosclerosis are disclosed. Formula (I) wherein n is 1 or 2; m is 2 or 3; q is 0 or 1; t is 0 or 1; R2 is alkyl having from 1 to 3 carbon atoms; R3 is hydrogen, halo, alkyl having from 1 to 3 atoms, or alkoxy having from 1 to 3 carbon atoms; A is phenyl, unsubstituted or substituted by 1 or 2 groups selected from: halo, alkyl having 1 or 2 carbon atoms, perfluoromethyl, alkoxy having 1 or 2 carbon atoms, and perfluoromethoxy; or cycloalkyl having from 3 to 6 ring carbon atoms wherein the cycloalkyl is unsubstituted or one or two ring carbons are independently mono-substituted by methyl or ethyl; or a 5 or 6 membered heteroaromatic ring having 1 or 2 ring heteroatoms selected from N, S and O and the heteroaromatic ring is covalently bound to the remainder of the compound of formula I by a ring carbon; and R1 is hydrogen or alkyl having 1 or 2 carbon atoms. Alternatively, when R1 is hydrogen, the biologically active agent can be a pharmaceutically acceptable salt of the compound of Formula (I)

The invention relates to a method for preparing a prostaglandin E1 lipid microsphere injection of a charging non-homogeneous phase (comprising a water phase, an oil / water interfacial film phase and an oil phase) dispersion system, of which the surface of the lipid microsphere can be charged with positive electricity or negative electricity. The prostaglandin E1 is alprostadil, of which the chemical structure comprises a basic skeleton of 20-carbon fatty acid with a 5-carbon ring and two side chains, wherein one side chain is provided with a hydrophilic carboxylic acid group, so that the prostaglandin E1 has the characteristic of light surface activity action. By utilizing the characteristic, and according to the formula and the preparation process provided in the invention, the prostaglandin E1 has an unique drug-carrying mode in a solution of lipid microsphere with the non-homogeneous phase dispersion system, and the prepared lipid microsphere injection is fundamentally different from an alprostadil injection(Kaishi, and is prepared by adopting the technology of the Japanese business corporation LTT Bio-Pharma Co., Ltd. already sold in markets, and the difference lies in that the drug-carrying mode is completely different, the content of degradation products in the preparation such as impurities is more than 50 percent lower than that of in the Kaishi, so that the prostaglandin E1 lipid microsphere injection and the alprostadil injection are fundamentally different. The invention relates to a method for preparing the prostaglandin E1 lipid microsphere injection and the drug-carrying characteristics thereof in a three-phase system; in the formula, 0.0001 to 0.1 weight portion of prostaglandin E1 is used as a drug, the prostaglandin E1 is added with auxiliary materials for medical purpose to prepare the prostaglandin E1 lipid microsphere injection, and the auxiliary materials for medical purpose comprises the following materials in portion by weight: 5 to 20.

The present invention provides nitrogen-containing fused cyclic derivatives represented by the following general formula or pharmaceutically acceptable salts thereof, or prodrugs thereof, which exhibit an excellent inhibitory activity in human SGLT and are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, postprandial hyperglycemia, impaired glucose tolerance, diabetic complications or obesity, in the formula one of R1 and R4 represents a group represented by the following general formula (S) (in which R5 and R6 represent H, OH, a halogen atom, etc.; Q represents an alkylene group etc.; and ring A represents an aryl group etc.), and the other represents H, OH, an amino group, etc.; R2 and R3 represent H, OH, an amino group, a halogen atom, and an optionally substituted alkyl group, etc.; A1 represents O, S, etc.; A2 represents CH or N; G represents a group represented by the following general formula (G-1) or (G-2) (E1 represents H, F or OH; and E2 represents H, F, a methyl group, etc.), and pharmaceutical compositions comprising the same, and pharmaceutical uses thereof.

A closed-loop insulin delivery system is described. More particularly, the presently disclosed insulin delivery system can comprise glucose-responsive vesicles that release insulin in response to hypoxia triggered by enzymatic reduction of glucose. In addition or as an alternative to insulin, the delivery system can release other diabetes treatment agents, such as non-insulin-based diabetes treatment agents. The vesicles can be prepared from a hypoxia sensitive polymer, such as a hypoxia-sensitive hyaluronic acid (HS-HA). The HS-HA can comprise hydrophobic groups that can be reduced in hypoxicenvironments to form hydrophilic groups. The vesicles can be loaded into microneedles and microneedle array patches for use in the treatment of diabetes or to otherwise regulate blood glucose levelsin subjects in need of such treatment.

The present invention is related to a single-chain insulin comprising the B- and the A-chain of human insulin or analogues thereof connected by a connecting peptide having from 3-35 amino acid residues, wherein the single-chain insulin comprises at least one PEG group attached to at least one lysine residue in the single-chain insulin molecule and / or to the B1 N terminal amino acid residue. The PEGylated single-chain insulins may comprise up to 4 PEG groups which may be the same or different.

A conjugate consisting of insulin-like growth factor binding protein 4 (IGFBP-4) and one or two polyethylene glycol) group(s), said polyethylene glycol) group(s) having an overall molecular weight of from about 30 to about 40 kDa is disclosed. This conjugate is useful for the treatment of cancer.

A fully manually powered infusion device provides both basal and bolus delivery of a liquid medicament to a patient. In some embodiments, the device includes a main reservoir that supplies the liquid medicament, an outlet port that delivers the liquid medicament to the patient, a basal dispenser that delivers a substantially constant flow of the liquid medicament to the outlet port, and a manually actuated bolus pump that delivers a bolus dose of the liquid medicament from the main reservoir to the outlet when actuated. The basal medicament supply delivers a volume of the liquid medicament from the main reservoir to the basal dispenser consonant with each actuation of the bolus pump.

The present invention relates to a crosslinkable composition crosslinkable by Real Michael Addition (RMA) reaction comprising a component with at least 2 activated unsaturated groups (hereafter referred to as the RMA acceptor groups) and a component with at least 2 acidic protons C-H in activated methylene or methine groups (hereafter referred to as the RMA donor groups) which components can react to form a crosslinked network. The composition comprises: f. Component(s) A having at least 2 acidic C-H donor groups in activated methylene or methine and having a pKa(A) between 10.5 and 14; g. Component(s) B having at least 2 activated unsaturated acceptor groups, wherein a molar ratio R of acceptor groups to donor groups is between 3:1 to 1:6 and which component(s) B react with component(s) A by Real Michael Addition (RMA) to form a crosslinked network; h. basic component(s) C being a salt of a basic anion X- from an acidic X-H group containing compound wherein X is N, P, O, S or C: iv. in an amount xc between 0.001 and 1 meq / (gr of components A, B, C, D), v. anion X- being a Michael Addition donor reactable with component B and vi. anion X- is characterized by a pKa(C) of the corresponding acid X-H of more than two units lower than the pKa(A) of the majority component A and being lower than 10.5; i. optional component(s) D comprising one or more acidic X'-H groups wherein X' is N, P, O, S or C: v. X' being a same or different group as group X in component C, vi. the X'- anion being a Michael Addition donor reactable with component B, vii. the pKa(D) of the X'-H group in component D being more than two units lower than pKa(A) of the majority component A and being lower than 10.5, viii. the equivalent ratio Rd / c of acidic X'-H groups in component D over basic anion X- in component C is between 1% and 5000%.

The invention relates to a novel chemical synthesis method of brominated PTP1B inhibitor and the application thereof in the medicine for curing type 2 diabetes, wherein the brominated PTP1B inhibitor has a chemical structural formula as follows: wherein a group connected with 2,2' and the number 3, 3' carbon of benzene ring is bromine atom; 4,4' and the number 5, 5' carbon of the benzene ring are connected with methoxyl; and the PTP1B inhibitor has a chemical name in English: Bis-(2,3-dibromo-4,5-dimethoxy-phenyl)-methane. The compound can enhance the sensibility of insulin receptor by restricting the activity of protein tyrosine phospholipase 1B and has favorable curing effect for type 2 diabetes in insulin resistance types.

The present invention relates to compounds of general formula I,wherein the groups R1, R2 and m are defined as in claim 1, which have valuable pharmacological properties, in particular bind to the GPR40 receptor and modulate its activity. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular diabetes type 2.

The invention provides a kaurene diterpene derivative shown as a general formula (I) and replaced by different groups at loci C-11, C-15, C-16 and C-19, a medicinal composition taking the kaurene diterpene derivative as an active ingredient, preparation methods thereof, and an application of the kaurene diterpene derivative to preparation of a type 1 11beta-hydroxysteroid dehydrogenase (11beta-HSD1) inhibitor. The invention further provides an application of a compound shown as a general formula (I) to preparation of a medicament for treating diabetes and relevant metabolic diseases (hypertension, obesity, senile dementia and the like).

The invention discloses a C3N4-Mt-SO3H composite material as well as preparation and application thereof. The C3N4-Mt-SO3H composite material is characterized in that carbon nitride is intercalated among montmorillonite layers, and sulfonic acid groups are grafted to the surfaces of montmorillonite. The preparation method of the C3N4-Mt-SO3H composite material is low in cost, simple to operate, and basically free from environmental pollution. The application of the C3N4-Mt-SO3H composite material used as a catalyst in hydrolysis hydrogenation preparation of sorbitol according to a cellulose-pot method is characterized in that the catalyst is capable of synchronously catalyzing cellulose to hydrolyze to obtain glucose and hydro-conversing glucose into sorbitol; moreover, the catalyst is recyclable.

A compound, which has a melanin-concentrating hormone antagonistic action and useful as an agent for preventing or treating obesity, and which is represented by the formula: wherein Ar is a cyclic group optionally having substituent(s); X is a bond or a spacer having a main chain of 1 to 6 atoms; R1 and R2 are the same or different and each is a hydrogen atom or a hydrocarbon group optionally having substituent(s), or R1 and R2 may form, together with the adjacent nitrogen atom, a nitrogen-containing heterocycle optionally having substituent(s); Y is a divalent hydrocarbon group optionally having substituent(s) (except CO); R3 is a hydrogen atom or a hydrocarbon group optionally having substituent(s); and ring A and ring B may further have substituents, and when ring B further has a substituent, the substituent may be linked to R1 to form a ring, or a salt thereof, or a prodrug thereof, is provided.

Compounds of formula (I), or pharmaceutically acceptable derivatives thereof, wherein: R1 represents H, C1-6-alkyl, C1-6alkyloxy, C3-8cycloalkyl, or halo; R2 represents H, C1-6alkyl (optionally substituted by R3), phenyl (optionally substituted by CN), or Het; R3 represents OH, CN, Het, —R4—C1-6alkyl, or CONR5R6; R4 represents —CO2—, or —O—; R5 and R6 independently represent H, C1-6alkyl (optionally substituted by OR7) or C3-8cycloalkyl; R7 represents H or C1-6alkyl; Het represents a five or six membered aromatic heterocyclic group containing (i) from one to four nitrogen heteroatom(s) or (ii) one or two nitrogen heteroatom(s) and one oxygen or one sulphur heteroatom or (iii) one or two oxygen or sulphur heteroatom(s), said heterocyclic group being optionally substituted by one or more groups selected from CN and C1-6 alkyl; R8 represents C1-6alkyl, C1-6alkyloxy, C3-8cycloalkyl, or halo; R9 and R10 independently represent H, C1-6alkyl, C1-6alkyloxy, CN, CF3 or halo; may be useful for treating endometriosis, uterine fibroids (leiomyomata), menorrhagia, adenomyosis, primary and secondary dysmenorrhoea (including symptoms of dyspareunia, dyschexia and chronic pelvic pain), or chronic pelvic pain syndrome.