Abstract: The present invention relates to an improved process for obtaining a precursor of an insulin or insulin derivative having correctly bonded cystine bridges in the presence of cysteine or cysteine hydrochloride and chaotropic auxiliary.

Abstract: There is disclosed a stable, virus-safe, pharmaceutical preparation comprising thiol-group-containing proteins which are heat-treated and processed such that at least 40% of the thiol groups are capable of being nitrosated, a method of preparing such preparations as well as the use of these preparations.

Abstract: Disclosed are peptide-based compositions and methods for inhibiting and modulating the actions of CXC intercrine molecules. The antileukinate peptides described inhibit IL-8, GRO and MIP2&bgr; binding to neutrophils and neutrophil activation. The peptides are particularly advantageous as they inhibit IL-8-induced enzyme release at a 25 fold lower concentration than is required to inhibit chemotaxis, which makes them ideal for treating various inflammatory diseases and disorders including, amongst others, Adult Respiratory Distress Syndrome (ARDS), cystic fibrosis and chronic bronchitis. The invention further includes methods for inhibiting tumor cell growth by employing selected members of the disclosed group of peptides to inhibit a-chemokine binding to the tumor cell.

Abstract: Microfabricated, asymmetrical, reservoir-containing particles for use in the oral delivery of biopolymer therapeutic agents such as peptides, proteins and oligonucleotides are disclosed. The particles are encapsulated in enteric-coated capsules or tablets to provide passage through the stomach and release of a suspension of the particles in the intestinal lumen. The particles have a selected shape, and uniform dimensions preferably in the 100 &mgr;m to 1 mm range. The reservoirs open to the face of the particle and are filled with a therapeutic agent and selected excipients. The excipients are selected to delay the dissolution/release of the agent from the particle reservoirs for 5-60 minutes after the particle is released in the intestinal lumen. Alternatively, the pore is plugged with an erodable material.

Abstract: Peptides are disclosed that inhibit the conversion of protease sensitive prion protein (PrPsen) to the protease resistant isoform (PrPres). These peptides comprise discrete fragments of prion proteins, and are shown to inhibit the in vitro conversion of PrPsen to PrPres in a cell-free system. Numerous peptides are disclosed that include at least two amino acid residues from the highly amyloidogenic region P113-120 of the PrP protein. None of these peptides conferred protease-resistance to the PrPsen molecules. The presence of residues 119 and 120 from the highly hydrophobic sequence AGAAAAGA (position 113 to 120) produced a particular inhibitory effect. The inhibition occurred with a high degree of specificity (e.g. with an IC50 of less than about 1000 &mgr;M).

Abstract: The subject of the invention is the use of a protein material whose rate of digestion has been reduced, for the preparation of an enteral composition which makes it possible to modulate the postprandial plasma amino acid level, said protein material having been previously treated so as to convert the fast-digesting proteins which it contains to slow-digesting proteins, characterized in that the slow-digesting protein material is a material containing microparticulate gelled proteins combined with polysaccharides under conditions of thermodynamic incompatibility.

Abstract: Novel synthetic Arg-Gly-Asp containing peptides which have high affinity and specificity for their receptors by virtue of restrictions on their stereochemical conformation. Such restrictions can be provided by cyclization, by inclusion into a constraining conformational structure such as a helix, by providing an additional chemical structure such as an amide or an enantiomer of a naturally occurring amino acid, or by other methods. In particular, there are provided cyclic peptides having increased affinity and selectivity for the certain receptors over that of linear, Arg-Gly-Asp-containing synthetic peptides.

Abstract: The present invention relates to biologically active peptides with reduced toxicity and methods of preparing them. The peptides of the invention, which can be unsubstituted or N-terminal substituted have the formula: wherein X is a biologically active amphiphilic ion channel-forming peptide or protein, T is a lipophilic moiety or hydrogen, and W is T or hydrogen. Preferably T is: wherein R is a hydrocarbon (alkyl or aromatic or alkylaromatic) having at least 2 and no more than 10 carbon atoms. T is preferably an octanoyl group. The peptides and proteins of the invention have improved antimicrobial and anti-tumor biological activity while exhibiting reduced toxicity. A preferred method of reducing toxicity involves the formation of related methane sulfonate derivatives or analogues. Additionally, the compounds of the invention may be used to treat sepsis, septic shock, and lung infections, such as those occurring in cystic fibrosis.

Abstract: The invention provides novel polypeptides and polynucleotides encoding such polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing such polypeptides to screen for antibacterial compounds.

Abstract: A homogenous substantially alcohol free composition of Cyclosporin which comprises a cyclosporin in a hydrophilic carrier medium comprising propylene glycol, esters of propylene glycol with C4 to C12 fatty acids and polyoxyethylene hydrogenated castor oils wherein the ingredients are present in the following range, Cyclosporin 1-25% w/w, Propylene Glycol 2.5-70% w/w, Esters of propylene glycol with C4 to C12 fatty acids 2.5-70% w/w and Polyoxyethylene hydrogenated Castor oils 2.5-70% w/w.

Abstract: Pharmaceutical compositions and methods are provided for the therapy of immunodeficient, immunodepressed or hyperactive immune states and for the prevention and treatment of opportunistic infections in such states comprising administering to a subject a pharmaceutically acceptable composition comprising as an active ingredient peptides having the formula R′-L-Glx-L-Glx-L-Lys-R″ and/or their pharmaceutically acceptable salts; wherein Glx is Gln or Glu.

Abstract: Peptides which mimic a loop on the &ggr;-chain that either interact with a cytokine or a &ggr;-chain partner receptor chain of a heterodimeric cytokine receptor are disclosed. The peptides consist of 5-25 amino acids and inhibit signal transduction mediated by cytokine:receptor binding of cytokines that bind to receptors that comprise a &ggr;-chain. Pharmaceutical compositions that comprise the peptides are disclosed. Methods of inhibiting signal transduction mediated by cytokine:receptor binding of cytokines that bind to receptors that comprise a &ggr;-chain, methods of inhibiting cytokine mediated cell growth, proliferation, function or activity, methods of treating patients suffering from a disease disorder or condition characterized by cytokine mediated cell growth, proliferation, function or activity and methods of preventing a condition characterized by cytokine mediated cell growth, proliferation, function or activity are disclosed.

Abstract: The object is to provide a promoting agent for bone formation, a therapeutic method for bone formation and a process for preparing a promoting agent for bone formation. A promoting agent for bone formation which comprises at least one of kistrin, echstatin, a peptide or polypeptide containing the amino acid sequence ArgGlyAsp in the molecule such as a peptide represented by Gly-Arg-Gly-Asp-Ser or a compound represented by the following general formula (IX) and so on, as well as a biologically acceptable salt thereof wherein R16 represents —N(R20)2 (R20 represents a hydrogen atom or a C1-C4 alkyl group), R17 represents a hydrogen atom or a C1-C4 alkyl group, R18 represents a hydrogen atom, a C1-C4 alkyl group and so on, R19 represents OH, NH2 and so on, Y represents —NH—, —O— or a direct bond, a represents 1-3, b represents 1 or 2, c represents 0 or 1 and d represents 0 or 1.

Abstract: Disclosed is a method for transporting neurologic therapeutic agents to the brain by means of the olfactory neural pathway and a pharmaceutical composition useful in the treatment of brain disorders.

Abstract: Lipoprotein complexes comprising a lipase-inhibiting protein component, and/or amylase-inhibiting protein component and a phospholipid component, compositions containing said complexes in combination with a polysaccharide component, pharmaceutical formulations and foods containing said complexes or compositions, processes for the preparation of said complexes and compositions, which are capable of reducing the weight increase following hypercaloric diets and of exerting hypocholesterolemizing, hypotriglyceridemizing and antioxidizing activities.

Abstract: The present invention relates generally to polypeptides that mimic or inhibit the biological activity of thrombospondin, and particularly to polypeptides in retroinverso form. These polypeptides may be used for their biological and pharmaceutical applications such as: (a) inhibiting the invasive and metastatic activity of melanoma cells, (b) promoting and inhibiting cellular attachment to tissue culture flacks, (c) promoting wound healing, angiogenesis, and implant acceptance, (d) agents for anti-platelet aggregation, (e) agents for antimalarial activity, and (f) diagnostic reagents in different therapeutic applications, as well as other related areas.

Abstract: The invention relates to a method of administering a fatty acid-acylated insulin or insulin analog by inhalation, a method for treating diabetes by administering a fatty acid-acylated insulin or insulin analog by inhalation, and a method for treating hyperglycemia by administering a fatty acid-acylated insulin or insulin analog by inhalation.

Abstract: Active compounds including sclareol-like and sclareolide-like compounds are usefull in methods of treating a wide variety of conditions and disorders, including those disorders caused by microbial (e.g., fungal and bacterial) infections, as well as those conditions and disorders caused by other mechanisms (e.g., activation of the adenylyl cyclase system). Pharmaceutical and cosmetic formulations comprising these active compounds are also useful in treating these disorders. One disorder that may be treated by the methods and formulations of the present invention is acne.

Abstract: The invention relates to new polypeptide compounds represented by the following formula [I]: wherein R1 is hydrogen, etc, R2 is hydrogen, etc, R3 is hydrogen, etc, and R4 is hydrogen, etc, or a salt thereof which have antimicrobial activities (especially, antifungal activities), inhibitory activity on &bgr;-1,3-glucan synthase, to process for preparation thereof, to a pharmaceutical composition comprising the same, and to a method for the prophylactic and/or therapeutic treatment of infectious diseases including Pneumocystis carinii infection (e.g. Pneumocystis carinii pneumonia) in a human being or an animal.

Abstract: Certain toxic compounds (T) such as, for example, compounds based upon diphtheria toxin, ricin toxin, pseudomonas exotoxin, &agr;-amanitin, pokeweed antiviral protein (PAP), ribosome inhibiting proteins, especially the ribosome inhibiting proteins of barley, wheat, corn, rye, gelonin and abrin, as well as certain cytotoxic chemicals such as, for example, melphalan and daunomycin can be conjugated to certain analogs of gonadotropin-releasing hormone to form a class of compounds which, when injected into an animal, destroy the gonadotrophs of the animal's anterior pituitary gland. Hence such compounds may be used to sterilize such animals and/or to treat certain sex hormone related diseases.