192 results about "Basal bolus" patented technology

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.

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 —NR^N1−; R^N1, if present, is independently —H or a substituent; R^N2 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 R^P1, R^P2, R^P5, and R^P4 is independently —H or a substituent; and additionally R^P1 and R^P2 taken together may be CH═CH—CH═CH—; and additionally R^P1 and R^P5 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—, —NR^N—, —C(═X)—, or —S(═O)₂—; either: exactly one linker moiety is —NR^N—, or: exactly two linker moieties are —NR^N—; 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 —NR^N—; X is independently ═O or ═S; each R^N is independently —H or a substituent; A is independently: C_6-14carboaryl, C_5-14heteroaryl, C_3-12carbocyclic, C_3-12heterocyclic; 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 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 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 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.

Isoxazoles of formula (A) or (B) are inhibitors of HSP90 activity, and useful for treatment of, for example cancers: (A), (B) wherein R₁, is a group of formula (IA): —Ar¹-(Alk¹)p-(Z)_r-(Alk²)_s-Q, wherein in any compatible combination Ar¹ is an optionally substituted aryl or heteroaryl radical, Alk¹ and Alk² are optionally substituted divalent C₁-C₆ alkylene or C₂-C₆ alkenylene radicals, p, r and s are independently 0 or 1, Z is -0-, —S—, —(C═O)—, —(C═S)—, —SO₂—, —C(═O)O—, —C(═O)NR^A—, —C(═S)NR^A—, —SO₂NR^A—, —NR^AC(═O)—, —NR^ASO₂— or —NR^A— wherein R^A is hydrogen or C₁-C₆ alkyl, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R₂ is (i) a group of formula (IA) above or (ii) a carboxamide radical; or (iii) a non aromatic carbocyclic or heterocyclic ring wherein a ring carbon is optionally substituted, and/or a ring nitrogen is optionally substituted by a group of formula -(Alk¹)p-(Z)_r-(Alk²)_s-Q wherein Q, Alk¹, Alk², Z, p, r and s are as defined above in relation to group (IA); and R₃ is hydrogen, optionally substituted cycloalkyl, cycloalkenyl, C₁-C₆ alkyl, C₁-C₆ alkenyl, or C₁-C₆ alkynyl; or a carboxyl, carboxamide, or carboxyl ester group.

The present invention discloses 5-membered heteroaryl ring compounds represented by formula [I], their prodrugs and pharmaceutically acceptable salts thereof, 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 (see formula I, see formula II), where R20, R21 , R22 and R25 are each H, etc.; E is aryl or heteroaryl 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 an alkylene group; and Z is an aryl group, etc. Compound [I] has superior protein tyrosine phosphatase 1B inhibitory activity and is useful as a therapeutic agent for diabetes, diabetic complications, hyperlipidemia, obesity and the like.

A C-phenyl 1-thioglucitol compound represented by the formula (I), a pharmaceutically acceptable salt thereof, or a hydrate of the compound or the pharmaceutically acceptable salt. (I) wherein X represents a hydrogen atom or a C1-6 alkyl group; Y represents a C1-6 alkylene group or -O-(CH2)n- (n represents an integer ranging from 1 to 5); and Z represents -CONHR or -NHCONHR (provided that, when Z represents -NHCONHR, n is not 1), where R represents a C1-6 alkyl group substituted by 1 to 3 groups independently selected from a hydroxyl group and -CONH2; and R represents a hydrogen atom or a C1-6 alkyl group substituted by 1 to 3 groups independently selected from a hydroxyl group and -CONH2. The compound, the salt or the solvate can inhibit the SGLT1 activity to prevent the absorption of glucose or the like, or can inhibit both the SGLT1 activity and the SGLT2 activity to prevent the absorption of glucose or the like and excrete a urine sugar, and is therefore useful as a prophylactic or therapeutic agent for diabetes.

The invention provides a glucose-sensitive self-regulated insulin release micro-gel carrier and a preparation method thereof. The preparation method of the glucose-sensitive self-regulated insulin release carrier comprises the following steps: performing free radical polymerization on three monomers namely 3-acryloyl aminophenylboronic acid, hydrophilic RGD polypeptide containing ethenyl functional groups and N-isopropylacrylamide to obtain a glucose-sensitive nano gel, and then combining the glucose-sensitive nano gel with insulin to obtain a medicine-loaded micro-gel. According to the glucose-sensitive self-regulated insulin release micro-gel carrier provided by the invention, the release of insulin can be automatically 'opened and closed' according to the changes of glucose concentrations at human body temperature.