Abstract: An angiogenesis inhibitor comprising a cysteine protease inhibitory compound. As the preferable cysteine protease inhibitory compound, epoxysuccinic acid compounds, peptide halohydrazide compounds, calpain inhibitory compounds, compounds of the formula (I) ##STR1## and compounds of the formula (VI) ##STR2## can be used. The angiogenesis inhibitor of the present invention suppresses new formation of blood vessels in the living tissues, so that it can be used as a superior therapeutic or prophylactic agent of angiogenesis associated with wound healing, inflammation, growth of tumor and the like; and angiogenesis as seen in diabetic retinopathy, prematurity retinopathy, retinal venous occlusion, senile discoid macular degeneration and the like, as well as for prevention of metastasis of tumors.

Abstract: Disclosed are lanthionine peptides having the structure ##STR1## methods of their preparation and use as pharmacologically active agents.

Abstract: The present invention relates to compounds represented by formula (I): ##STR1## wherein Z represents Gly or Cys; X represents an (.alpha.-amino acid residue; Y represents a natural calcitonin moiety, a partial natural calcitonin peptide moiety, or a natural calcitonin-like peptide moiety; m represents an integer of 5-8, .alpha.-amino acid residues represented by X being the same or different; and n represents an integer of 0-3; provided that when m is 5, the sequence of 4 C-terminal residues of --(X).sub.m -- is different from the sequence of the third to sixth amino acids of natural calcitonin, and pharmaceutically acceptable salts thereof.

Abstract: Modified hydrolyzed vegetable protein microspheres and methods for their preparation and use as oral delivery systems for pharmaceutical agents are described.

Abstract: Carrier compounds and compositions therewith which are useful in the delivery of active agents are provided. Methods of administration and preparation are provided as well.

Abstract: A pharmaceutical composition comprising a physiologically active polypeptide, an absorption promoting agent consisting of a combination of an organic acid and a fatty acid sucrose ester in admixture with a pharmaceutically acceptable carrier or diluent, which is suitable for oral administration and for application to the oral cavity, by which the polypeptide can sufficiently be absorbed through the intestinal tract or the mucous membrane in the oral cavity and exhibit the physiological activities without being suffered from enzymolysis.

Abstract: The present invention provides a method for counteracting preeclampsia, eclampsia of pregnancy and preterm labor in a pregnant female mammal treated by administering thereto calcitonin gene-related peptide (CGRP) or its analogues including CGRP/adrenomedullin or their peptide or receptor-based analogues, or in combination with a progestin, and with or without a nitric oxide substrate, or a nitric oxide donor or both, optionally in further combination with one or more of a cyclooxygenase inhibitor, a PGI.sub.2 -mimetic, a thromboxane (TXA.sub.2) inhibitor, a compound possessing TXA.sub.2 -agonistic, and TXA.sub.2 -inhibiting properties, a compound possessing TXA.sub.2 -antagonistic and PGI.sub.2 -mimetic activities, and a TXA.sub.2 antagonist. CGRP, progesterone and some of the nitric oxide substrate and donor compounds are naturally occurring compounds. As such these agents do not have the same toxicity and allergy problems as the foreign substances that are currently used for similar purposes.

Abstract: A nasally administrable composition having a physiologically active peptide dispersed homogeneously in and adsorbed homogeneously onto a unique carrier. The composition contains an effective amount of physiologically active peptide dispersed homogeneously in and adsorbed homogeneously onto a mucosa protecting and/or tissue repairing agent, e.g., gefarnate, aceglutamide aluminum, sucralfate, L-glutamine, sofalcone, teprenone, plaunotol, rebamipide, aldioxa, cetraxate or troxipide.

Abstract: Fatty acid derivatives of sulfhydryl-containing compounds (for example, sulfhydryl-containing peptides or proteins) comprising fatty acid-conjugated products with a disulfide linkage are employed for delivery of the compounds to mammalian cells. This modification markedly increases the absorption of the compounds by mammalian cells relative to the rate of absorption of the unconjugated compounds, as well as prolonging blood and tissue retention of the compounds. Moreover, the disulfide linkage in the conjugate is quite labile in the cells and thus facilitates intracellular release of the intact compounds from the fatty acid moieties.

Abstract: The present invention relates polypeptide analogs which have agonist or antagonist or tissue selection properties relative to parathyroid hormone (PTH), parathyroid hormone-like protein (PLP) or parathyroid-related protein (PTHrP). The serine amino acid at position 3, the glutamine amino acid at position 6, the histidine amino acid at position 9 or combinations thereof are substituted by other natural or synthetic amino acids. Preferably, a human PTH fragment of about 34 amino acids is sufficient for pharmacological activity. These polypeptides are useful as agonists or antagonists in the treatment of a human being for disease conditions of cancer, osteoporosis, hypercalcemia, or hyperparathyroid disease conditions. The invention also concerns a method of performing certain assays using the modified peptides, and based on the results of the assays falling within preset limits, selecting those modified peptides which shall be useful in the treatment of disease conditions.

Abstract: Pharmaceutical compositions of matter adapted for intravaginal administration comprise a biologically active polypeptide, an absorption promoter, such as an anionic and/or nonionic surfactant or a nonionic surfactant and an aliphatic carboxylic acid, optionally an animal and/or vegetable protein and a nontoxic pharmaceutically acceptable carrier or diluent therefor, in a formulation suitable for intravaginal administration. Preferred compositions comprise calcitonin as the biologically active polypeptide. Preferred absorption promoters are anionic surfactants, e.g., sodium lauryl sulfate, and the combination absorption promoter of a nonionic surfactant and a medium chain aliphatic carboxylic acid or its salt, e.g. polyoxyethylenealkylphenylether and a medium chain aliphatic carboxylic acid.

Abstract: The improved hybrid calcitonin has a peptide segment in human calcitonin and a peptide segment in calcitonin derived from animals other than humans, such as eel, salmon and chicken. Each of the human or human analog calcitonins and the calcitonins derived from animals other than humans may be either native calcitonin or an analog thereof. The hybrid calcitonin has the outstanding advantage that it exhibits biological activities as strong as eel, salmon and chicken calcitonin while causing no side effects including nausea, disorders in the functions of the digestive tract or antigenicity.

Abstract: Methods for treating conditions associated with elevated, inappropriate or undesired post-prandial blood glucose levels are disclosed which comprise administration of an effective amount of an amylin agonist alone or in conjunction with other anti-gastric emptying agents. Methods for reducing gastric motility and delaying gastric emptying for therapeutic and diagnostic purposes are also described.

Abstract: Polypeptides, polynucleotides, fragments thereof, and monoclonal antibodies thereto are provided for antigen-specific and antigen-non-specific glycosylation inhibiting factor and a method for recombinant production of biologically active polypeptides from a structural gene encoding the polypeptide.

Abstract: Compositions and methods for reducing food intake, suppressing appetite and controlling body weight are provided. Such compositions may include an amylin agonist and a CCK agonist or a hybrid peptide.

Abstract: A procedure for obtaining carbocalcitonin comprising the condensation of fragment 1, a docosapeptide corresponding to the carboxamide end of the carbocalcitonin sequence, conveniently protected and anchored on resin, with fragment 2 or 3, a nonapeptide corresponding to the amino end of the salmon calcitonin sequence, with a ready-formed cycle between the Asu and Ser residua, and the treatment of the complete peptide skeleton (fragment 6 or 7) with an acid to free the totally deprotected peptide from the resin.

Abstract: Compositions and methods for stabilization and oral delivery of human calcitonin are described. An aqueous liquid composition for stable storage of human calcitonin comprises an aqueous mixture of SDS and an organic acid. An nonaqueous liquid composition for stable storage of human calcitonin comprises about 90-100% by volume of a mixture of C.sub.8 /C.sub.10 mono- and di-glycerides and about 0-10% by volume of a polar, nonaqueous solvent. Both of these stabilized human calcitonin formulations provided significant intestinal absorption of calcitonin.

Abstract: Derivatized calcitonin molecules, pharmaceutical compositions comprising derivatized calcitonins, and methods of reducing serum calcium in a patient using the derivatized calcitonins are disclosed. The molecules are characterized by a derivatized amino terminus formed by combining a calcitonin with a cyclic, polycyclic or heterocyclic moiety. Multimeric forms of the molecules are also disclosed.

Abstract: The invention provides isolated, biologically active native calcitonin mimetics and related methods. These small 16 and 17 amino acid proteins mimic the interaction of calcitonin on its receptor, and also exhibit bone resorptive inhibiting activity.

Abstract: New polypeptides comprising 32 amino acids, process for preparation thereof, application thereof as drugs and pharmaceutical preparations containing, as active ingredient, one or a plurality of said polypeptides. These polypeptides are used as active principles for new drugs, particularly indicated for osteoporoses of various origins.

Abstract: This invention relates to compounds of the formula: ##STR1## wherein: A' is absent, Asn, Gln, Ala or Abu;A is absent or a D- or L-amino acid chosen from Arg, HArg, (Me.sub.2)Arg, (Et.sub.2)Arg, Abu, Ala, Gly, His, Lys, or an .alpha.-R' substituted derivative thereof, Dtc, Tpr and Pro;B is a D- or L-amino acid chosen from Arg, HArg, NArg, (Me.sub.2)Arg, (Et.sub.2)Arg and Lys or an .alpha.-R' substituted derivative thereof;Q is absent or a D or L amino acid chosen from Tyr, (Alk)Tyr, Phe, (4'W)Phe, HPhe, Phg, Pro, Trp, His, Ser, (Alk)Ser, Thr, (Alk)Thr, (Alk)Cys, (Alk)Pen, Ala, Val, Nva, Met, Leu, Ile, Nle and Nal, or an .alpha.-R' substituted derivative thereof;M is absent or Gly or a D- or L-amino acid chosen from Glu, Phe, Pro, Lys and Ser or, provided n is 1, B-Gly-Glu-Q;W is halogen or Alk;R' is Alk or PhCH.sub.2 ; ##STR2## wherein Z.sub.1 and Z.sub.2 are linked via a covalent bond between L.sup.1 and L.sup.2 ; or Z.sub.1 and Z.sub.

Abstract: The present invention relates to a novel method for making a predetermined, desired peptide in transgenic animals and can be advantageously used for the production of large quantities of the desired peptide. More particularly, the invention concerns the engineering of a transgenic animal having an artificial gene, which is controlled by globin locus control region (LCR) and which encodes a fusion protein, in which the desired peptide is joined via a cleavable peptide linker to a globin polypeptide. The erythrocytes of the transgenic animal express the fusion globin which is incorporated into hemoglobin produced by the host cell. The desired peptide can be obtained from a hemolysate of the red cells of the transgenic animals by enzymatic or chemical cleavage at the linker.

Abstract: The invention provides fibrillated calcitonin for use in treating calcium deficiency diseases.

Abstract: A stable aqueous solution of human calcitonin (hCT) which remains free of hCT fibrils for at least 24 hours at 25.degree. C. which comprises water, hCT and a cellulose derivative and/or an acid, the type of acid and the amount of acid being so chosen as to achieve said stability in the absence of a salt or a buffer.

Abstract: Peptide derivatives containing one or more substituents separately linked by an amide, amino or sulfonamide bond to an amino group on either the N-terminal end or side chain of a biologically active peptide moiety. The peptide derivatives have relatively enhanced biological activity when compared to the corresponding peptide alone.

Abstract: Peptide derivatives selected from (i) a calcitonin peptide and a LHRH antagonist peptide modified by at least one sugar residue and/or at least one short polyhydroxy compound or derivative, and (ii) a calcitonin peptide modified by at least one formyl and/or at least C.sub.3-5 alkyl attached to an amino group other than a N-terminal amino group, and (iii) a calcitonin peptide modified by a combination of said substituents, with the provisos thati) when the calcitonin peptide comprises at least one sugar residue a), this sugar residue is attached by a coupling other than a direct N-glycosidic bond to an .omega.-amino group of an .omega.-amino substituted side chain in the 24 position, andii) when the LHRH antagonist comprises at least one sugar residue a), this sugar residue is an Amadori sugar residue attached by a coupling other than a direct N-glycosidic bond to an .omega.-amino group of an .omega.

Abstract: The invention provides a polypeptide of calcitonin analogue and use thereof. The polypeptide has such an amino acid sequence that proline-amide residue (Pro-NH.sub.2) at C-terminal of native eel calcitonin is substituted to a homoserine amide residue (Hse.multidot.NH.sub.2).

Abstract: A procedure for the preparation of salmon calcitonin comprising the condensation of fragment 1(SEQ ID NO: 1), a docosapeptide corresponding to the carboxamide end of the salmon calcitonin sequence conveniently protected and anchored on resin, with fragment 2(SEQ ID NO:2), a decapeptide corresponding to the amino end of the salmon calcitonin sequence conveniently protected and with a disulphide bridge ready formed between the two cysteines, and the treatment of the complete peptide skeleton (fragment 6 (SEQ ID NO:6)) with an acid to liberate the totally deprotected peptide from the resin.

Abstract: Methods for treatment of diabetes and other insulin-requiring conditions by administering insulin and a calcitonin with or without amylin, and methods for treatment of hypoglycemic conditions by administering a calcitonin alone or in combination with glucagon and/or an amylin, and related compositions.

Abstract: A peptide of the following general formula is subjected to cyclization reaction to produce a cyclic peptide, preferably a synthetic calcitonin derivative (elcatonin) which is a useful medicine. ##STR1## (wherein A and B form a peptide of the formula Ser-Asn-Leu-Ser-Thr (SEQ ID NO: 43); X means a hydroxyl group, a carboxy-protecting group, an amino acid residue or a peptide residue; provided that the side-chain carboxyl group of .alpha.-L-aminosuberic acid is condensed with an amino acid or a peptide). The cyclic peptide can be obtained by subjecting a peptide of the above general formula to (1) cyclization reaction by chemical condensation, (2) cyclization reaction in the presence of an alkali metal salt and (3) reactions using the techniques of liquid phase synthesis and solid phase synthesis in combination.

Abstract: Methods of preparing a peptide having a C-terminal amide group from peptides having a C-terminal carboxyl group are provided.

Abstract: The present invention is directed to Cholic, Chenodeoxycholic and deoxycholic acid derivatives of a peptide having the sequence: Pro-Arg-Thr-Asn-Thr-Gly-Ser-Gly-Thr-Pro-amide and use thereof in inducing analgesia.

Abstract: New pharmaceutical compositions containing a calcitonin as active principle and suitable fop opal administration in the form of perbuccal and sublingual tablets ape described, in which the active principle is homogenized with a mixture of solid excipients, said excipients consisting of a diluent, a lubricant, a disintegrating agent in the case of sublingual tablets, and a binder in the case of perbuccal tablets. Said compositions enable the same pattern of hematic levels to be obtained fop the same unit dose as obtainable by conventional intramuscular administration.

Abstract: A calcitonin originated from the ultimobranchial gland of cartilaginous fishes and having a blood calcium-decreasing activity has the following amino acid sequence: H-Cys-Thr-Ser-Leu-Ser-Thr-Cys-Val-Val-Gly-Lys-Leu-Ser-Gln-Gln-Leu-His-Lys- Leu-Gln-Asn-Ile-Gln-Arg-Thr-Asp-Val-Gly-Ala-Ala-Thr-Pro-NH.sub.2, where the cysteine residues in the peptide may be linked together through a disulfide bond. The novel peptide exhibits an excellent blood calcium-decreasing activity and an excellent chondrocyte differentiation-promoting activity and is useful as a therapeutic agent for hypercalcemia, osteoporosis, Paget's disease, and the like.

Abstract: In this invention, a peptide of the following general formula is subjected to cyclization reaction to produce a cyclic peptide, preferably a synthetic calcitonin derivative (elcatonin) which is a useful medicine. ##STR1## (wherein A and B form a peptide of the formula Ser-Asn-Leu-Ser-Thr (SEQ ID NO: 47); X means a hydroxyl group, a carboxy-protecting group, an amino acid residue or a peptide residue; provided that the side-chain carboxyl group of .alpha.-L-aminosuberic acid is condensed with an amino acid or a peptide).The cyclic peptide can be obtained by subjecting a peptide of the above general formula to (1) cyclization reaction by chemical condensation, (2) cyclization reaction in the presence of an alkali metal salt and (3) reactions using the techniques of liquid phase synthesis and solid phase synthesis in combination.

Abstract: Processes for synthesizing polypeptides containing substantially non-antigenic polymers, preferably poly(alkylene glycols) in specifically predetermined sites are disclosed. Polypeptides prepared by such processes acre also disclosed.

Abstract: A method for administering a therapeutically effective amount of a biologically active substance to the circulatory system of a mammal including administering a pharmaceutical composition having a total volume of 1-1000 .mu.1 to a nasal mucosal membrane of the mammal, the pharmaceutical composition including the therapeutically effective amount of the biologically active substance dissolved or suspended in a volume of 1-1000 .mu.1 of a n-glycofurol-containing vehicle including at least one n-glycofurol represented by the formula: ##STR1## wherein n is from 1 to 8, so that upon administration of the pharmaceutical composition to the nasal mucosal membrane, absorption of the biologically active substance through the mucosal membrane and into the blood stream of the mammal rapidly takes place and thereby allows the biologically active substance to exert its therapeutic effect.

Abstract: Synthetic amylin and amylin analogs which have high biological activity and which are substantially free from deletion peptides and other contaminating peptides are provided. Also provided are methods for the solid phase peptide synthesis of amylin and amylin analogs.

Abstract: The invention provides recombinant plasmids containing in DNA sequences coding for human preproparathyroid hormone. The invention further provides microorganisms, for example E. coli, transformed by these plasmids. The invention also provides a plasmid for insertion into yeast and a transformed yeast in which the plasmid contains DNA coding for parathyroid hormone. Parathyroid hormone is then secreted by the transformed yeast. Further the invention provides alternate polypeptides having parathyroid hormone activity, including PTH analogs, fragments and extensions, and provides alternate leader sequences and secretion signal sequences which can be used in the present invention. Finally, there are provided methods for purification of the secreted PTH hormone and/or derivatives.

Abstract: Use of amylin, or variants of amylin, as well as amylin agonists, for the treatment of bone disorders, in particular osteoporosis, Paget's disease, and malignant deposits in bone, bone loss of malignancy or endocrine disorders or autoimmune arthritides or immobility and disuse, and in other conditions where a hypocalcaemic effect is of benefit. Functional peptide fragments of amylin, or a variant of amylin or amylin fragment, are provided as well as a soluble amylin, amylin fragments, or variants thereof, or a lyophilized product, or an oral formulation for use alone, or in combination with other agents, including insulin (or insulin-stimulating agents, including but not limited to the sulfonylureas) and estrogens, for the treatment of disorders of bone or calcium balance.

Abstract: A pharmaceutical preparation for application of an effective amount of one or more biologically active substance(s) to a mucosal membrane of a mammal comprising an n-glycofurol represented by the formula I: ##STR1## wherein n is 1 to 4 in an amount from: 0.1-30% preferably 0.1-20% most preferably 1-15% in water, or in vegetable oil or n-ethylene glycol(s) represented by formula II:H(OCH.sub.2 CH.sub.2).sub.p OHwherein p is 2 to 8, or in a mixture thereof. Nasal administration of the preparation produces a high plasma concentration of the pharmaceutically active substance(s) nearly as rapid as by i.v. administration.

Abstract: This invention relates to human gene related peptide pharmaceutical compositions containing the peptide and the method of treating hypertension with said pharmaceutical composition.

Abstract: A biologically active peptide associated with diabetes and designated herein "amylin" and processes for preparing it and assaying for it and for Type 2 diabetes are disclosed. The invention includes peptides having the amino acid sequence KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY, substantially homologous sequences of amino acids, proamylin, as well as biologically active subfragments and conservative mutations. The peptide may be prepared from diabetic pancreata by solubilization of amyloid and isolation of the peptide by gel filtration and reverse phase chromotography. Amylin may also be synthesized, or it may be produced by recombinant DNA techniques using the disclosed nucleic acid sequences.

Abstract: Synthetic hypocalcemic peptides which are superior in biological properties to native calcitonins as clinically useful agents. The peptides comprise analogues of native calcitonins having amino acid additions at the N-terminal position which, either alone or together with substitutions, and deletions at other residues, act to improve potency, prolong duration of the hormonal effect, and increase oral or nasal bioavailability. Methods are provided for the synthesis of these peptides.

Abstract: A stabilized conjugated peptide complex comprising a peptide conjugatively coupled to a polymer including lipophilic and hydrophilic moieties, wherein the peptide may for example be selected from the group consisting of insulin, calcitonin, ACTH, glucagon, somatostatin, somatotropin, somatomedin, parathyroid hormone, erythropoietin, hypothalamic releasing factors, prolactin, thyroid stimulating hormones, endorphins, enkephalins, vasopressin, non-naturally occurring opioids, superoxide dismutase, interferon, asparaginase, arginase, arginine deaminease, adenosine deaminase, ribonuclease, trypsin, chymotrypsin, and papain.

Abstract: Peptides of formula I ##STR1## in which R is hydrogen or acetyl and X is an amino acid sequence of formula -Ser-Leu-Asp-Ser-Pro-Arg-Ser- (Ia) or of formula -Arg-Ile-Ile-Ala-Gln- (Ib), and salts of such compounds, can be used for the treatment of diseases involving bone degeneration.

Abstract: Production of human calcitonin precursor structural gene, the insertion of this gene in a vector system, the cloning thereof and a process for the production of authentic human calcitonin using recombinant DNA biotechnology.

Abstract: A freeze-dried pharmaceutical composition for parenteral administration which includes a therapeutically effective amount of a calcitonin, as the active ingredient, and human albumin.The injectable solution which is obtained by dissolving the freeze-dried composition in a physiologically acceptable solvent is also described.

Abstract: Compounds and methods for blocking the effects of diabetes-associated peptide, or "amylin", a hormone found in the amyloid masses of Type 2 diabetics. 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 substituted peptides or sub-peptides of amylin or CGRP, cross-linked amylin and amylin agonists, synthetic amylin, anti-amylin receptor antibodies and anti-idiotype antibodies, and antibodies directed to amylin and amylin agonist active sites. Other antagonists include organic compounds which can be screened and assayed for anti-amylin effects by disclosed methods.

Abstract: A high-absorbable transvaginal preparation having excellent absorbability of the active ingredient, which comprises a biologically active polypeptide and an absorption promoter comprising a polyoxyethylenealkylphenyl ether and one or more compounds selected from the group consisting of an N-acylamino acid, cholic acids, pectic acid, taurine, saccharin, glycyrrhizic acid, aspartame, or a salt thereof.