55 results about "Enkephalin" patented technology

A complex is provided for the treatment of neurogenic conditions having the formula: where R1 is M is a metal ion Ca(II), Mg(II), Cu(II) or Ni(II); n is an integer 1 or 2; R is BBB peptide, transferrin, membrane transporter peptide, TAT peptide, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptidegluconate, L-lactate, L-leucine, L-tryptophan, and L-glutamate; and R is coupled to M through a carboxylate moiety. Magnesium (II) represents the preferred metal ion as magnesium is known to have neuroprotective effects. The metal ion is in part chelated by a non-steroidal anti-inflammatory drug that does not inhibit platelet activity and includes salicylate and ibuprofenate. The complex also includes a ligand operative in transport across the blood brain barrier. A process for making an inventive complex includes the stoichiometric addition of ligands containing carboxylate groups to a solution of the metal ion. In instances where the metal ion is magnesium (II), a stoichiometric ratio of 1:1:1 is found between the non-steroidal anti-inflammatory ligand:magnesium (II):transporter ligand.

Disclosed are a method and a corresponding pharmaceutical composition for treating damaged cartilage and subchondral bone. Neurogenic compounds in general and neuropeptides in particular have been found to be highly effective in stimulated repair of cartilage and bone damaged due to traumatic injury, ligament disease, and disuse. Preferred active ingredients for use in the method and corresponding pharmaceutical composition include calcitonin gene-related peptide (CGRP), cholecystokinin (CCK), dynorphin, enkephalin, galanin, neuropeptide Y (NPY), neurotensin, somatostatin, substance P (SP), thyrotropin-releasing hormone (TRH), vasoactive intestinal peptide (VIP).

A compound is provided that has the formula NH2CH2CH2CH2C(O)N—R   (I) where R is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine blood brain barrier (BBB) peptide, membrane translocating protein, TAT peptides, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptidetransferrin, glucosylamnine, amino saccharin, lactylamine, leucine, tryptophan, glutamate and amino cholines.

Disclosed is an abstract convex lower-bound estimation based protein structure prediction method. The method includes: firstly, aiming for high-dimensional conformational spatial sampling problems for proteins, adopting a series of transform methods to transform an ECEPP / 3 force field model into an increasing radial convex function in unit simple constraint conditions; secondly, based on an abstract convex theory, proving and analyzing to give out a supporting hyperplane set of the increasing radial convex function; thirdly, constructing a lower-bound underestimate supporting plane on the basis of population minimization conformation subdifferential knowledge under a differential evolution population algorithm framework; fourthly, by the aid of a quick underestimate supporting plane extreme point enumeration method, gradually decreasing a conformational sampling space to improve sampling efficiency; fifthly, utilizing the lower-bound underestimate supporting plane for quickly and cheaply estimating an energy value of an original potential model to effectively decrease evaluation times of a potential model objective function; finally, verifying effectiveness of the method by methionine-enkephalin (TYR1-GLY2-GLY3-PHE4-MET5) conformational spatial optimization examples. The abstract convex lower-bound estimation based protein structure prediction method is high in reliability, low in complexity and high in computation efficiency.

A compound is provided that has the formula NH2CH2CH2CHR1C(O)N—R  (I) where R1 is p-chlorophenyl, R is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine blood brain barrier (BBB) peptide, membrane translocating protein, TAT peptides, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptide transferrin, glucosylamine, amino saccharin, lactylamine, leucine, tryptophan, glutamate and amino cholines.

A method for skin antiaging treatment comprising administering Botulinum toxin to an area of facial and / or neck skin, combined with the administration of a cosmetic or pharmaceutical composition comprising a cosmetically or pharmaceutically effective amount of at least one peptide derived from the SNAP-25 protein and / or at least one enkephalin-derived peptide, and at least one cosmetically or pharmaceutically acceptable excipient or adjuvant.

A complex is provided for the treatment of neurogenic conditions having the formula:where R1 isM is a metal ion Ca(II), Mg(II), Cu(II) or Ni(II); n is an integer 1 or 2; R is BBB peptide, transferrin, membrane transporter peptide, TAT peptide, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptidegluconate, L-lactate, L-leucine, L-tryptophan, and L-glutamate; and R is coupled to M through a carboxylate moiety. Magnesium(II) represents the preferred metal ion as magnesium is known to have neuroprotective effects. The metal ion is in part chelated by a non-steroidal anti-inflammatory drug that does not inhibit platelet activity and includes salicylate and ibuprofenate. The complex also includes a ligand operative in transport across the blood brain barrier. A process for making an inventive complex includes the stoichiometric addition of ligands containing carboxylate groups to a solution of the metal ion. In instances where the metal ion is magnesium(II), a stoichiometric ratio of 1:1:1 is found between the non-steroidal anti-inflammatory ligand:magnesium(II):transporter ligand.

A compound is provided that has the formulaNH2CH2CH2CH2C(O)N—R  (I)where R is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine blood brain barrier (BBB) peptide, membrane translocating protein, TAT peptides, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptidetransferrin, glucosylamnine, amino saccharin, lactylamine, leucine, tryptophan, glutamate and amino cholines.

A compound is provided that has the formulaNH2CH2CH2CHR1C(O)N—R   (I)where R1 is p-chlorophenyl, R is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine blood brain barrier (BBB) peptide, membrane translocating protein, TAT peptides, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptide transferrin, glucosylamine, amino saccharin, lactylamine, leucine, tryptophan, glutamate and amino cholines.

Disclosed are a method and a corresponding pharmaceutical composition for treating damaged ligaments. Neurogenic compounds in general and neuropeptides in particular have been found to be highly effective in stimulated repair of ligaments damaged due to traumatic injury, ligament disease, and disuse. Preferred active ingredients for use in the method and corresponding pharmaceutical composition include calcitonin gene-related peptide (CGRP), cholecystokinin (CCK), dynorphin, enkephalin, galanin, neuropeptide Y (NPY), neurotensin, somatostatin, substance P (SP), thyrotropin-releasing hormone (TRH), vasoactive intestinal peptide (VIP).

A compound of the formulawhere R1 is H, C1–C4 alkyl and OH; R2 in is H, C1–C4 alkyl and OH; R3 is H and C1–C4 alkyl; R4 is H and C1–C4 alkyl; n is an integer between 0 and 2 inclusive; R5 is a nullity, NHR7C(O)—, C6H4—, C6H4—O—; R7 is C2–C6 alkyl; and R6 is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine, blood brain barrier (BBB) peptide, membrane translocating peptide, TAT peptides, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptidegluconate, transferrin, glucosylamine, amino saccharin, saccharin ester, lactylamine, leucine, tryptophan, amino glutamate and amino cholines.

A compound of the formula where R1 is H, C1-C4 alkyl and OH; R2 in is H, C1-C4 alkyl and OH; R3 is H and C1-C4 alkyl; R4 is H and C1-C4 alkyl; n is an integer between 0 and 2 inclusive; R5 is a nullity, NHR7C(O)—, C6H4—, C6H4—O—; R7 is C2-C6 alkyl; and R6 is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine, blood brain barrier (BBB) peptide, membrane translocating peptide, TAT peptides, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptidegluconate, transferrin, glucosylamine, amino saccharin, saccharin ester, lactylamine, leucine, tryptophan, amino glutamate and amino cholines.

A method for skin antiaging treatment including administering Botulinum toxin to an area of facial and / or neck skin, combined with the administration of a cosmetic or pharmaceutical composition having a cosmetically or pharmaceutically effective amount of at least one peptide derived from the SNAP-25 protein and / or at least one enkephalin-derived peptide, and at least one cosmetically or pharmaceutically acceptable excipient or adjuvant.

The invention provides an expression cassette comprising a DNA sequence encoding amino acids 1-99 of human preproenkephalin, a DNA sequence encoding a precursor of a carboxy-amidated peptide flanked by dibasic cleavage sites and optionally a DNA sequence encoding a marker protein (such as Enhanced Green Fluorescent Protein (GFP)) all in operable linkage and under control of a promoter. Where the encoded precursor of a carboxy-amidated peptide is an agonist for an opioid receptor, the invention further provides a method of treating neuropathic pain by administering the gene transfer vector comprising such an expression cassette to a patient. The invention also provides a method for detecting a peptide having a desired effect comprising introducing a library of DNA sequences encoding one or more precursors of carboxy-amidated peptides into host cells; expressing the carboxy-amidated peptides encoded in the library to provide expression products; and screening from the polypeptide expression products for the desired effect.

The present invention relates to pharmaceutical compositions for treating neoplasias in an animal or human comprised of a carrier and therapeutically effective amounts of at least one chemotherapeutic agent along with the biotherapeutic endogenous pentapeptide Met-enkephalin, referred to as opioid growth factor. Also provided are methods of treating neoplasias in an animal or human in need of such treatment, comprising the administration to the animal or human therapeutically effective amounts of a pharmaceutical composition comprised of a carrier and therapeutically effective amounts of at least one neoplasia-treating agent, such as a chemotherapeutic agent or radiation, along with opioid growth factor.

A compound provided by the present invention includes an endocannabinoid, endocannabinoid derivative, or endocannabinoid analog moiety covalently bonded to a biologically active peptide. One example of an inventive compound described is a conjugate of an endocannabinoid, endocannabinoid derivative, or endocannabinoid analog moiety covalently coupled to an opioid peptide, such as an endorphin, enkephalin, dynorphin or endomorphin. Also detailed are processes for making the described conjugates and pharmaceutical compositions including such compounds.

The present invention provides a pharmaceutical composition that includes a) one or both of i) a peptide ligand that binds a zeta receptor and ii) at least one cancer chemotherapeutic agent; and b) a sustained release formulation. The invention also provides a combination including at least a portion of a tissue comprising one or more cells harboring a zeta receptor, such as a cancer cell or a precancerous cell, in contact with a pharmaceutical composition of the invention. Additionally the invention provides a method of treating a pathology that responds to a peptide ligand that binds a zeta receptor that includes a step of contacting a tissue characteristic of the pathology and containing cells harboring a zeta receptor, with a pharmaceutical composition of the invention. The invention further provides methods of inhibiting proliferation or metastasis of a cancer in a subject, including a) surgically excising a tumor characterizing the cancer from the subject; b) ensuring maximal removal of a tumor margin from the tumor site; and c) disposing a pharmaceutical composition of the invention upon a tissue remaining at a tumor margin wherein the tissue contains one or more tumor cells (such as a cancer cell or a precancerous cell) harboring a zeta receptor. The peptide ligand of a zeta receptor may be an enkephalin, an endorphin, a dynorphin, or a derivative thereof. Additionally the pharmaceutical composition may include one or more cancer chemotherapeutic agents.

The invention discloses polyethylene glycol derivatives of an enkephalin analogue, a preparation method, and a composition containing the same. The polyethylene glycol derivatives of an enkephalin analogue of the invention comprises an enkephalin analogue and polyethylene glycol covalently connected to a C end of the enkephalin analogue, wherein the enkephalin analogue has the following structure: X-Try-Y1-Gly-Phe-Y2-Y3-Z, and X is H or Ac; Y1 is D-Ala or Gly; Y2 is D-Ala or Met or Leu; Y3 is Cys or high Cys or Lys or Arg or His, and is a residue modified by PEG; Z is OH or NH2. The polyethylene glycol derivatives of the enkephalin analogue provided by the invention can be used to prepare analgesic drugs or precursor compounds of the drugs.

The invention discloses a low-frequency therapeutic apparatus for drug detoxification, which is regulated and controlled by a computer and is equipment for the drug detoxification and solves the problem of poor effects of healing with drugs for the drug detoxification in the past. The low-frequency therapeutic apparatus for the drug detoxification, regulated and controlled by the computer, comprises a power source and a shell, the shell is internally provided with a controller and the input end of the controller is connected with the computer while the output end of the controller is connected with a therapeutic electrode. By virtue a method of acupuncture points and meridians in the traditional Chinese medical science, a pulse signal generated by the driving of the controller by the computer passes through the therapeutic electrode and a skin electric shocking pulse is directly adopted to stimulate acupuncture points of a human body for treatment, thus promoting the releasing of enkephalin in the human body, further relieving the withdrawal symptoms of opiate narcotics and having the effects of pain easing and spasmolysis and better withdrawal effect than amidone methadone. The therapeutic apparatus of the invention has safe and reliable application, no pain, no side effect, and obvious effects for relieving addiction and controlling relapse. The computer is used for regulating and controlling so as to realize simple operation and accurate curative effect.

The invention belongs to the technical field of treating tumor by adopting an immunization therapy method, and particularly relates to application of naloxone or hydrochloride thereof or composition of the naloxone or the hydrochloride thereof with methionine enkephalin in preparing a drug for treating cancer. The application of the naloxone in preparing the drug for treating the cancer is characterized in that the naloxone and the hydrochloride thereof or the composition of the naloxone and the hydrochloride thereof and the methionine enkephalin are applied to preparing the drug for treating the cancer. The drug can be prepared into tablets, capsules, spraying agent, aerosol and eye drops. The application aims to fill the blank on the research of treating the cancer by using the naloxone and the hydrochloride thereof or / and the composition of the naloxone and the hydrochloride thereof and the methionine enkephalin.

Disclosed are a method and a corresponding pharmaceutical composition for treating damaged ligaments. Neurogenic compounds in general and neuropeptides in particular have been found to be highly effective in stimulated repair of ligaments damaged due to traumatic injury, ligament disease, and disuse. Preferred active ingredients for use in the method and corresponding pharmaceutical composition include calcitonin gene-related peptide (CGRP), cholecystokinin (CCK), dynorphin, enkephalin, galanin, neuropeptide Y (NPY), neurotensin, somatostatin, substance P (SP), thyrotropin-releasing hormone (TRH), vasoactive intestinal peptide (VIP).

A topical opioid paradigm was developed to determine analgesic peripheral effects of morphine. Topical morphine as well as peptides such as [D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO) produced a potent, dose-dependent analgesia using the radiant heat tailflick assay. The topical drugs potentiated systemic agents, similar to the previously established synergy between peripheral and central sites of action. Local tolerance was rapidly produced by repeated daily topical exposure to morphine. Topical morphine tolerance was effectively blocked by the N-Methyl-D-Aspartate (NMDA) receptors antagonist MK801 and ketamine given either systemically or topically. NMDA receptor antagonists reversed pre-existing morphine tolerance. The activity of topical NMDA antagonists to block local morphine tolerance suggests that peripheral NMDA receptors mediate topical morphine tolerance. Morphine was cross tolerant to [D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO), but not to morphine-6 beta -glucuronide, implying different mechanisms of action. These observations have great importance in the design and use of opioids clinically. Topical pharmaceutical compositions comprising an analgesic that functions through an opiate receptor and an NMDA receptor antagonist for producing analgesia without inducing tolerance are described.

A method for promoting a sustained increased level of T-cell production in immunocompromised subjects in which method enkephalin peptides are administered according to an intermittent dose schedule. In particular, the method involves treatment of immunocompromised patients which includes the administration of enkephalin, either alone or in conjunction with other therapies, in an initial dosage regimen, with periodic booster dosages of enkephalin as necessary to maintain sustained immune system response.

The invention provides a multi-site modified enkephalin and neurotensin (8-13) coupled cycled hybrid peptide, a compounding method and an application thereof and relates to a cycled hybrid peptide, the compounding method and the application thereof. The invention aims to solve the problems of inferior anti-enzymolysis capacity and non-ideal anti-neuropathic pain effect of present opioids. The hybrid peptide is a hybrid peptide 1, a hybrid peptide 2, a hybrid peptide 3 or a hybrid peptide 4. The preparation method comprises the following steps: 1) pre-treating 'Fmoc' protected Wang resin; 2) removing 'Fmoc' protecting groups; 3) triggering condensation reaction of amino acid; 4) prolonging peptide chain; 5) forming a disulfide bond; 6) cutting peptide chain from the resin; 7) desalting andpurifying crude peptide. According to the invention, the biological stability of hybrid peptide can be enhanced and an anti-neuropathic pain effect can be endowed, through multi-site unnatural amino acid substitution and cyclizing modification. The hybrid peptide provided by the invention can be used for preparing drugs for relieving neuropathic pain.

The invention relates to the technical field of disinfection products, in particular to a cloud rose aromatherapy disinfection spray and a preparation method thereof. The cloud rose aromatherapy disinfection spray is prepared from the following components in parts by weight: 94 to 96 parts of rosa damascena flower water, 2 to 3 parts of a compound quaternary ammonium salt, 2 to 3 parts of grapefruit extract, 5 to 10 parts of common vladimiria root volatile oil, 5 to 10 parts of an emulsifier and 1000 parts of water. The rosa damascena flower water and the composite quaternary ammonium salt areadded, the aromatherapy effect is good while disinfection and sterilization are conducted, the rose water is pleasant in fragrance and fragrant in smell, after natural aromatic hydrocarbon enters thebrain from olfactory nerves, frontal lobes of the brain can be stimulated to secrete two hormones of endorphin and enkephalin, and the spirit is in the most comfortable state; and the rose water andthe grapefruit extract also have good soothing and nourishing effects on the skin.

A compound is provided that has the formula (II):where R1 in each occurrence is independently H, or C1-C4 alkyl; R2 is a nullity or CH—CH3, R3 is a nullity or C(O)—R6—NH; R6 is C2-C6 alkyl, (CH2CH2—O)n, or (CH(OH)CH2)n; n is an integer of between 1 and 4; R4 is a nullity or NH—R6—C(O); and R5 is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine, blood brain barrier (BBB) peptide, membrane translocating peptide, TAT peptides, endocannabinoids 1 & 2, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptide transferrin, glucosyl ester, lactic acid, leucine, tryptophan, glutamic acid.

The invention relates to application of combination of low-dose naltrexone and methionine-enkephalin to preparation of an anti-cancer drug. The low-dose naltrexone and the methionine-enkephalin are combined via an opioid receptor on the surface of a cell of an immunity system of a body, so that effects of stimulating activation and proliferation of immune cells and improving an immune function can be realized. In addition, the combination of the low-dose naltrexone and the methionine-enkephalin is used for preparing the drug for treating cancers, so that a novel tumor biotherapy method with a breakthrough curative effect is formed, and the drug has the advantages of low dosage and side effect, high activity and safety, and the like.

The invention discloses an acupoint electrical stimulation method and an acupoint electrical stimulation device for auxiliary treatment of inflammatory pain. The acupoint electrical stimulation method is characterized by outputting a bidirectional symmetric rectangular pulse current with output frequency of 2 / 120Hz, when the frequency is 2Hz, the wave width is 400mu s, when the frequency is 120Hz, the wave width is 100mu s, and sparse waves and dense waves each last 3 seconds, thereby achieving pain alleviation for inflammatory pain. The device for implementing the acupoint electrical stimulation method comprises a pulse generator and electrodes. The acupoint electrical stimulation method and the acupoint electrical stimulation device can obviously increase the secretion of central nerve endogenous enkephalin and beta-endorphin, inhibits generation of peripheral IL-1beta, has anti-inflammatory and pain alleviating effects, is conductive to alleviating the inflammatory pain, offers intelligent operation for a patient to relieve pain by using an instrument on his own, and can improve life quality of patients with pain.

An application of methionine enkephalin in preparing the medicine for treating the blood in biotherapy of tumor is disclosed. Its treating method includes a culture step after said medicine is added to the blood to be treated for reproducing more cellulotoxic cells, macrophages, natural killing cells, interleukin-2, and gamma-interferons, resulting in higher power to kill tumor cells.