Abstract: The present invention is directed to a macrocapsule for encapsulating microcapsules containing biologically active material, such as living cells or free living cells, to make the system more biocompatible by decreasing the surface area and surface roughness of microencapsulated biological materials; increasing mechanical stability of microencapsulated biological materials; enhancing cytoprotectivity by increasing diffusion distance of encapsulated biological material from cytotoxins secreted in vivo; providing retrievability of microencapsulated material; and providing a system of sustained release of the cellular products. The method for producing such a macrocapsule containing the microcapsules is also disclosed.

Abstract: A process for the long term modification and regulation of lipid and carbohydrate metabolism--generally to reduce obesity, insulin resistance, and hyperinsulinemia or hyperglycemia, or both (these are the hallmarks of noninsulin dependent, or Type II diabetes)--by administration (i.e., by oral, sublingual or parenternal administration) to a vertebrate, animal or human, of a dopamine agonist, e.g., bromocriptine. Administration of the bromocriptine is made over a limited period at a time of day dependent on the normal circadian rhythm of insulin resistant and insulin sensitive members of a similar species. Insulin resistance, and hyperinsulinemia and hyperglycemia, or both, can be controlled in humans on a long term basis by such treatment inasmuch as the short term daily administration resets hormonal timing in the neural centers of the brain to produce long term effects.

Abstract: This invention describes methods of treating or preventing diabetes in obese type II diabetic patients. Specifically, methods of treating obese type II diabetics with varying levels of endogenous circulating leptin are claimed.

Abstract: The present invention relates to human insulin derivatives having a protracted profile of action in which the A21 and B3 amino acid residues are, independently, any amino acid residue which can be coded for by the genetic code except Lys, Arg and Cys; Phe.sup.B1 may be deleted; the B30 amino acid residue is (a) a non-codable, lipophilic amino acid having from 10 to 24 carbon atoms in which case an acyl group of a carboxylic acid with up to 5 carbon atoms is bound to the E-amino group of Lys.sup.B29 ; (b) any amino acid residue which can be coded by the genetic code except Lys, Arg and Cys, in which case a lipophilic substituent is bound to the E-amino group of Lys.sup.B29 ; or (c) deleted, in which case a lipophilic substituent is bound to the E-amino group of LyS.sup.B29 ; and any Zn.sup.2+ complexes thereof; provided that when the B30 amino acid residue is Thr or Ala, the A21 and B3 amino acid residues are both Asn and Phe.sup.B1 is present, then the insulin derivative is a Zn.sup.2 + complex.

Abstract: The coordinated therapeutic use of L-carnitine, lower alkanoyl L-carnitines or the pharmacologically acceptable salts thereof with resveratrol, resveratrol derivatives or resveratrol-containing natural products is disclosed for producing a medicament for the prophylaxis and treatment of cardiovascular disorders, peripheral vascular diseases and peripheral diabetic neuropathy.

Abstract: Fluorine-containing benzoylguanidines of the formula I ##STR1## in which R.sup.1, R.sup.2 and R.sup.3 have the meanings indicated, and their physiologically acceptable salts, have antiarrhythmic properties and act as inhibitors of the cellular Na.sup.+ /H.sup.+ antiporter, for example.

Abstract: A method of lowering plasma levels of Lp(a) or inhibiting the generation of apo(a) in a human by administering an effective amount of a compound of the formula: ##STR1## wherein n is 0, 1 or 2:R.sup.1 is hydrogen, alkyl, alkanoyl, cycloalkanoyl, (alkoxy)alkanoyl, aroyl, aryloxycarbonyl;R.sup.2 is hydrogen, hydroxy, halo, alkoxy, alkanoyloxy, cycloalkanoyloxy, (alkoxy)alkanoyloxy, aroyloxy, aryloxycarbonyloxy;R.sup.3 is pyrrolidinyl or piperidinyl;or a pharmaceutically acceptable salt thereof;and a pharmaceutically acceptable excipient, is disclosed.

Abstract: The invention is a method and composition for treating diabetes using an extract derived from Heracleum lanatum and a species of Populus.

Abstract: There is disclosed compounds and pharmaceutical compositions that are a resolved R or S (preferably R) enantiomer of an .omega.-1 alcohol of a straight chain alkyl (C.sub.5-8) substituted at the 1-position of 3,7-disubstituted xanthine. The inventive compounds are effective in modulating cellular response to external or in situ primary stimuli, as well as to specific modes of administration of such compounds in effective amounts.

Abstract: A method for prophylaxis or treatment of diabetes, which comprises administering to a patient with diabetes an effective amount of a dihydrochalcone derivative of the formula ?I!: ##STR1## wherein Ar is an aryl group, R.sup.1 is hydrogen atom or an acyl group, R.sup.2 is a hydrogen atom, an acyl group or .alpha.-D-glucopyranosyl group, or R.sup.1 and R.sup.2 may combine together to form a substituted methylene group, R.sup.3 and R.sup.4 are each a hydrogen atom or an acyl group, OR.sup.5 is a protected or unprotected hydroxy group or a lower alkoxy group, or a pharmaceutically acceptable salt thereof.

Abstract: Alkyl-benzoylguanidines of the formula I ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 have the meanings given, and physiologically acceptable salts thereof show antiarrhythmic properties and act as inhibitors of the cellular Na.sup.+ /H.sup.+ antiporter.

Abstract: A process for the long term modification and regulation of lipid and glucose metabolism--generally to reduce obesity, insulin resistance, and hyperinsulinemia or hyperglycemia, or both (these being the hallmarks of noninsulin dependent, or Type II diabetes)--by administration to a vertebrate, animal or human, of a dopamine agonist and a prolactin stimulator. The dopamine agonist and prolactin stimulator are administered in daily dosages, respectively, at a time of day dependent on the normal circadian rhythm of fat and lean members of a similar species. Decreases in body fat deposits result by treatment of an obese species on a daily timed sequence based on circadian rhythms of the peak prolactin, or peak prolactin and peak glucocorticosteroid, blood level established for lean insulin sensitive members of a similar species.

Abstract: Compositions for trans-mucosal delivery, e.g. intranasal, include a lysophosphatidyl-glycerol compound as the adsorption enhancer. The preferred compounds for delivery are insulin and calcitonin.

Abstract: A method for preparation of biodegradable polymeric drug delivery devices using relatively low temperatures and non-aqueous solutions which is particularly useful with polyanhydrides, thermolabile drugs, and in forming multi-layered devices.In a first embodiment, the polymer is dissolved in a volatile organic solvent, the drug is dispersed or dissolved in the polymer solution, the mixture is suspended in an organic oil, and the organic solvent is extracted into the oil, creating microspheres. The preferred polymers are polyanhydrides since they are biodegradable and have been proven to be useful in vivo.In a second embodiment, the polymer is dissolved in organic solvent with or without the drug, and the mixture is suspended in glycerol. The suspension is frozen and the organic solvent slowly evaporated.

Abstract: A process for the long term modification and regulation of lipid and glucose metabolism--generally to reduce obesity, insulin resistance, and hyperinsulinemia or hyperglycemia, or both (these being the hallmarks of noninsulin dependent, or Type II diabetes)--by administration to a vertebrate, animal or human, of a dopamine agonist and a prolactin stimulator. The dopamine agonist and prolactin stimulator are administered in daily dosages, respectively, at a time of day dependent on the normal circadian rhythm of fat and lean members of a similar species. Decreases in body fat deposits result by treatment of an obese species on a daily timed sequence based on circadian rhythms of the peak prolactin, or peak prolactin and peak glucocorticosteroid, blood level established for lean insulin sensitive members of a similar species.

Abstract: In a preferred embodiment, drugs having pharmacological properties which are useful in the medicinal therapy of fibrotic disease for the reparation and prevention of fibrotic lesional tissues, such drugs including as active ingredient(s) one or more N-substituted 2-(1H) pyridone(s) and/or N-substituted 3-(1H) pyridones. The composition of this invention is novel as an anti-fibrotic drug, namely, as an agent for treating fibrosis. Any existing compounds have not been shown to be effective for the reparation and prevention of fibrotic lesions.

Abstract: Novel 1,4,5-substituted imidazole compounds and compositions for use in therapy as cytokine inhibitors.

Abstract: A process for the long term modification and regulation of lipid and glucose metabolism--generally to reduce obesity, insulin resistance, and hyperinsulinemia or hyperglycemia, or both (these being the hallmarks of noninsulin dependent, or Type II diabetes)--by administration to a vertebrate, animal or human, of a dopamine agonist and a prolactin stimulator. The dopamine agonist and prolactin stimulator are administered in daily dosages, respectively, at a time of day dependent on the normal circadian rhythm of fat and lean members of a similar species. Decreases in body fat deposits result by treatment of an obese species on a daily timed sequence based on circadian rhythms of the peak prolactin, or peak prolactin and peak glucocorticosteroid, blood level established for lean insulin sensitive members of a similar species.

Abstract: Antibody methods for blocking the effects of diabetes-associated peptide, or "amylin", a hormone found in the amyloid masses of Type 2 diabetics, are disclosed. This putative hormone has been discovered to function both to inhibit insulin secretion and to inhibit glycogen synthesis. Regulation is accomplished by blocking the binding of amylin or amylin agonists, including calcitonin gene related peptide (CGRP), or biologically active sub-peptides thereof. Inhibitors include antibodies directed to amylin and amylin agonist active sites. Other antagonists include anti-idiotype antibodies directed to antibodies directed to amylin.

Abstract: This invention relates to a method for modifying metabolism in a vertebrate animal which entails the administration of pantethine or cysteamine at a predetermined time daily. The method is useful in the treatment of hyperglycemia, glucose intolerance, insulin resistance, and hyperinsulinemia.

Abstract: Disclosed are methods for improving various aberrant metabolic indices in mammals including humans by administration of muscarinic (particularly M1) receptor antagonists alone or in combination with prolactin inhibiting compounds. Preferably the administration takes place at a predetermined time (or, if a combination of muscarinic receptor antagonist and prolactin inhibitor is used, at different predetermined times) during a 24-hour period when the administration is effective (or its effect more pronounced). The invention has application in the treatment of lipid and glucose metabolism disorders.

Abstract: A drug delivery composition for intranasal delivery comprises a plurality of bioadhesive microspheres and active drug associated with each microsphere, at least 90 wt % of the microspheres having a diameter in the range 0.1 .mu.m to 10 .mu.m. The microspheres may be of starch, gelatin, dextran, collagen or albumin. Suitable drags include peptides, such as insulin, and antigenic vaccine ingredients. The composition may additionally comprise an absorption enhancer. The microspheres are administered m the nasal cavity by a means such that the product of the square of the microsphere diameter and the flow rate is greater than 2000 .mu.m.sup.2.liters/min.

Abstract: Substituted sulfonimidamides, processes for their preparation, their use as a medicament or diagnostic, and medicament comprising themSulfonimidamides of the formula I ##STR1## in which at least one of the three substituents R(1), R(2) and R(3) is a benzoylguanidine, and in which the other substituents have the meanings indicated in the claims, are outstandingly suitable as medicaments having action on the cardiovascular system; that is as antiarrhythmic pharmaceuticals having a cardioprotective component as well as for treating ischemically induced damage; also in operative interventions, such as organ transplantation.

Abstract: Benzoylguanidines of the formula I ##STR1## wherein R.sup.1 and R.sup.2 have the meanings indicated herein, and their physiologically acceptable salts, show anti-arrhythmic properties and act as inhibitors of the cellular NA.sup.+ /H.sup.+ antiporter.

Abstract: Disclosed are methods for improving various aberrant metabolic indices in mammals including humans by administration of muscarinic (particularly M1) receptor antagonists alone or in combination with prolactin inhibiting compounds. Preferably the administration takes place at a predetermined time (or, if a combination of muscarinic receptor antagonist and prolactin inhibitor is used, at different predetermined times) during a 24-hour period when the administration is effective (or its effect more pronounced). The invention has application in the treatment of lipid and glucose metabolism disorders.

Abstract: Vasopressin analogues of formula (I) ##STR1## wherein X is (S)-2-amino-2-methyl-butanoic acid (CaMeAbu) or Valine (Val), Y is Thienylalanine (Thi) or Methionine (Met), Z is D-Phenylalanine (D-Phe) or D-Thienylalanine (Thi) or D-Tyrosine (D-Tyr), are disclosed. Pharmaceutical preparations comprising a vasopressin analogue of the invention as active ingredient are disclosed and exemplified by oral preparations, nasal preparations, and intravenous preparations. The vasopressin analogues of the invention are intended for use as a medicament, specially an antidiuretic agent. The antidiuretic agent is preferably used for the treatment of diabetes insipidus or enuresis.

Abstract: The invention relates to the use of R-(+)-.alpha.-lipoic acid, R-(-)-dihydrolipoic acid or their metabolites, salts, esters and amides for the synthesis of drugs for the treatment of diabetes mellitus of types I and II, compensated and decompensated insulin resistance and sequelae or late complications of diabetes mellitus, such as cataracts, polyneuropathy, nephropathy, as well as sequelae or late complications of insulin resistance. These drugs mentioned can also be used advantageously in combination with other antidiabetic drugs, particularly with insulin, and/or other additives or stabilizers or adjuvants, such as vitamin E, vitamin C, NADH, NADPH and ubiquinone.The invention furthermore relates to the use of R-(+)-.alpha.-lipoic acid, R-(-)-dihydrolipoic acid or their metabolites, as well as their salts, esters and amides for the preparation of drugs for the treatment of diseases with limited function of or a lowered content of the glucose transporters.

Abstract: Agonist analogues of amylin and related pharmaceutical compositions, and methods of treatment of diabetes and other insulin-requiring states, as well as methods of treatment of hypoglycemia, are provided.

Abstract: The subject invention pertains to methods of using 4-guanidinobutyramide, or a physiologically-acceptable salt thereof, in a mammal or human to improve blood circulation.

Abstract: Biodegradable, protein microspheres for in vivo release of a biologically active agent, as well as agricultural and environmental applications. The microspheres can be administered orally, intravenously, or subcutaneously for subsequent release. By selecting particular size ranges and the specific protein used to form the microsphere, it is possible to target the microspheres to a cell types such as macrophages, or to effect localized absorption of the microspheres to regions such as the mucosal membranes of the mouth, gastrointestinal tract, or urogenital areas. Larger forms of the microspheres can also be made using standard techniques of the desirable degradation properties.

Abstract: A pharmaceutical composition comprising a polydeoxyribonucleotide of random sequence formula is disclosed, andP.sub.v, (dAp).sub.w, (dGp).sub.x, (dTp).sub.y, (dCp).sub.zwhereinP.sub.v is 1-5 phosphoric radicals,(dAp).sub.w is 12-24 deoxyadenylic monomers,(dGp).sub.x is 10-20 deoxyguanylic monomers,(dTp).sub.y is 13-26 deoxythymidylic monomers, and(dCp).sub.z is 10-20 deoxycytidylic monomers;wherein the polydeoxyribonucleotide has:a homogenous anodic mobility in electrophoresis,an extinction coefficient E.sup.1%.sub.1 cm at 260.+-.1 nm=220.+-.10,an extinction coefficient E.sub.230 /E.sub.260 =0.45.+-.0.04,a molar extinction coefficient (referred to phosphorous), .epsilon.(P)=7750.+-.500,a rotary power ?.alpha.!.sup.20.degree..sub.D =53.degree..+-.6, anda reversible hyperchromicity as percent in native DNA h=15.+-.5, in combination with a pharmaceutically acceptable carrier or diluent. A method of treating or preventing a diabetic neuropathy using the polydeoxyribonucleotide is also shown.

Abstract: Novel terpenoid-type quinones which can be obtained from Pycnanthus spp., processes for obtaining the novel terpenoid-type quinones and methods for their use as hypoglycemic agents, for example, in the treatment of diabetes are described. In a preferred embodiment, the novel terpenoid-type quinones are obtained from the leaves and stems of Pycnanthus angolensis. As agents for the treatment of diabetes, the novel terpenoid quinones are useful for treating insulin-dependent (type I) and/or non-insulin-dependent (type II) diabetes.

Abstract: Therapeutic compositions comprising an effective amount of at least one carbonyl trapping agent alone or in combination with a therapeutically effective of a co-agent or medicament are disclosed. The compositions are used to treat a mammal suffering from a neurological disease characterized by covalent bond crosslinking between the nerve cells, other cellular structures and their intracellular and extracellular components, with disease induced carbonyl-containing aliphatic or aromatic hydrocarbons present in mammals.

Abstract: An oral dosage composition for intestinal delivery comprising (A) a biologically active ingredient; and (B) zonula occludens toxin, as well as a method for the use of the same.

Abstract: AICA riboside and prodrugs of AICA riboside are provided which lower blood glucose for the treatment of various pathologic conditions, including hypoglycemia, insulin deficiency, insulin resistance diabetes and Syndrome X. Prodrugs of AICA riboside provide AICA riboside in an orally bioavailable form. The use of adenosine kinase inhibition and ZMP enhancement for lowering blood glucose are also described.

Abstract: A method for encapsulating biological substances in biocompatible microcapsules is disclosed, the method comprising:(a) maintaining a coating-forming liquid film sheet transverse to a vertical plane, said sheet comprising an organic polymerizable monomer liquid,(b) causing droplets comprising biological substances in an aqueous medium to fall downwardly through said liquid film sheet to form microcapsules comprising cores of said droplets coated by said film,(c) permitting said microcapsules to fall downwardly from said liquid film sheet, and(d) polymerizing said liquid film coatings during descent of said microcapsules below said sheet to form a permeable polymer coating of a sufficient structural integrity so that said microcapsules are self-supporting.

Abstract: Orally or rectally administrable formulations of biologically active material comprise a water-in-oil microemulsion, wherein the hydrophilic phase of the microemulsion comprises the biologically active material and the hydrophobic phase comprises chylomicra or material capable of forming chylomicra in the intestinal mucosa after administration. The biologically active material may be any of a wide range of substances including insulin, calcitonin and somatotrophin or growth hormone. Formulations of the invention are particularly suitable for the oral administration of insulin in the treatment of diabetes.

Abstract: A synthetic insulin mimetic compound is disclosed. Small synthetic amines of disaccharides, such as 2-deoxy-2-amino-galactopyranosyl pinitol are shown to mimic the action of insulin and to modulate its action.

Abstract: Methods and pharmaceutical compositions for modifying the immune response of a mammal to a specific antigen are provided. The methods include treating an antigen presenting cell to enhance expression of a major histocompatibility complex molecule and reacting the treated antigen presenting cell with the antigen extracorporeally to form an antigen-associated antigen presenting cell.

Abstract: The invention covers a method of implanting a living donor cell into a host animal without inflammatory response or rejection of the donor cell by the host animal, by obtaining an uncoated particle of a biocompatible, temperature-independent gel that encapsulates the living donor cell, wherein the uncoated particle provides a molecular weight cutoff that prevents host animal immune cells from entering the particle, yet does not have to prevent entry of host animal IgG and complement into the particle, and implanting the uncoated particle into the host animal.

Abstract: Oxalate-degrading enzymes and bacteria were encapsulated for both enteric and intraperitoneal administration. We have shown that via alginate microencapsulation of Oxalobacter formigenes, enzymatic activity was retained for several months. A new process was developed which strengthened the alginate microcapsules and their tolerance to citrate treatment. Much smaller (30-50 .mu.m) alginate microcapsules were made for injection as means of implantation. For oral administration, multi-encapsulated microspheres of cellulose acetate phthalate in poly-2-vinylpyridine (pKa=3.5) were prepared to protect the enzymes from gastric juices.

Abstract: Methods for the treatment of metabolic and/or cardiovascular disorders comprising administering to a human in need thereof a therapeutically effective amount of a composition comprising dichloroacetic acid or a pharmaceutically acceptable salt or derivative thereof and a pharmaceutically acceptable mixture of carbonate and bicarbonate ions, the weight ratio of dichloroacetic acid, derivative or salt thereof to the mixture of carbonate and bicarbonate ions being in the range of from about 100:1 to about 0.01:1.

Abstract: A method of chronic modification of cell barrier properties by exposing a cell to a modification-effective amount of IGF-I for at least about 7 days wherein the modification effective amount is between about 50 .mu.g/kg and less than about 500 .mu.g/kg is disclosed. Further disclosed is a method of chronic amelioration or reversal of insulin resistance as well as a method of diagnosing and screening for rhIGF-I sensitive cell barrier properties.

Abstract: A process for the long term modification and regulation of linid and glucose metabolism--generally to reduce obesity, insulin resistance, and hyperinsulinemia or hyperglycemia, or both (these being the hallmarks of noninsulin dependent, or Type II diabetes)--by administration to a vertebrate, animal or human, of a dopamine agonist and a prolactin stimulator. The dopamine agonist and prolactin stimulator are administered in daily dosages, respectively, at a time of day dependent on the normal circadian rhythm of fat and lean members of a similar species. Decreases in body fat deposits result by treatment of an obese species on a daily timed sequence based on circadian rhythms of the peak prolactin, or peak prolactin and peak glucocorticosteroid, blood level established for lean insulin sensitive members of a similar species.

Abstract: Adverse inflammatory reactions can be treated by administrating to an organism a composition having diglucosylamine as the active ingredient. The preferred compound is di-Beta-D-glucopyranosylamine. A simple method for making diglucosylamine in high purity is obtained by reacting glucose, a nitrogen containing base, and either methanol or ethanol to form the diglucosylamine and then recovering the diglucosylamine preferably with the use of charcoal. The preferred diglucosylamine, di-Beta-D-glucopyranosylamine, has extraordinary anti-inflammatory activity. It can be formulated with a pharmaceutically acceptable carrier to make pharmaceutical compositions which are effective in treating inflammations. This pharmaceutical composition can also be used to treat adverse inflammatory reactions that are the result of the disruptions of a dynamic network of cellular mechanisms in organisms.

Abstract: The use of extracts from Cryptolepis sp. or quindoline alkaloids such quindoline and cryptolepine contained therein as hypoglycemic agents, as well as methods for obtaining the hypoglycemic agents are described. According to a preferred embodiment, the extracts are derived from Cryptolepis sanguinolenta. As hypoglycemic agents, the extracts or quindoline alkaloids such as quindoline or cryptolepine are useful for treating insulin-dependent (type I) and non-insulin-dependent (type II) diabetes.

Abstract: There is disclosed compounds and pharmaceutical compositions that are a resolved R or S (preferably R) enantiomer of an .omega.-1 alcohol of a straight chain alkyl (C.sub.5-8) substituted at the 1-position of 3,7-disubstituted xanthine. The inventive compounds are effective in modulating cellular response to external or in situ primary stimuli, as well as to specific modes of administration of such compounds in effective amounts.

Abstract: Disclosed herein are methods for regulating or ameliorating lipid and glucose metabolism and reducing in a vertebrate animal body fat stores, insulin resistance, hyperinsulinemia, hyperglycemia, hyperlipidemia, elevated blood lipoproteins (such as triglycerides and cholesterol including chylomicrons, VLDL and LDL) and/or increasing in the subject the plasma HDL. The methods comprise administration or timed administration of inhibitors of dopamine beta hydroxylase (DBH).

Abstract: A method for treating and/or preventing Type I diabetes mellitus in mammals and humans by administration of at least one of the following: (i) gamma interferon, (ii) an analog of gamma interferon or (iii) an inducer of gamma interferon thereof is taught. The use of gamma interferon, analogs thereof, or gamma interferon inducers to prevent recurrent Type I diabetes mellitus in transplant subjects is also provided.

Abstract: Derivatives of glucagon-like peptide I (GLP-1) and especially GLP-1(7-36) have been found to have insulinotropic activity. The invention pertains to the use of GLP-1(7-36) for the treatment of type II diabetes mellitus.