118 results about "Tissue selectivity" patented technology

The invention provides instruments and methods for prophylactic treatment of an osteoporotic vertebral body or for treating a vertebral compression fracture (VCF). In one exemplary method, a probe system uses a high speed rotational elastomeric cutter having an optional expandable abrasive surface for abrading or cutting at least one path or region within vertebral cancellous bone. Irrigation and aspiration sources are included in the probe system for removing abraded bone debris. In one embodiment, the high speed rotational abrader uses a tissue-selective abrading surface that abrades or cuts bone but does not cut soft tissue. In another embodiment, an expandable abrading surface allows the treatment of bone with low pressures to create paths or spaces without explosive expansion forces known in prior art balloon procedures that are designed to crush and compact cancellous bone in a vertebra. After the creation of a path or space, an in-situ hardenable bone cement volume is introduced into each path or space to support the vertebra.

The invention provides instruments and methods for prophylactic treatment of an osteoporotic vertebral body or for treating a vertebral compression fracture (VCF). In one exemplary method, a probe system uses a high speed rotational cutter for abrading or cutting a plane within vertebral cancellous bone. Optional irrigation and aspiration sources are included in the probe system for removing abraded bone debris. In one embodiment, the high speed cutter uses a tissue-selective abrading surface that abrades or cuts bone but does not cut soft tissue. After the creation of a weakened cut plane in the bone, reduction of the fracture requires reduced forces.

The present invention provides compositions and methods for treatment of conditions and diseases associated with excessive or inappropriate noncancerous tissue growth. In certain embodiments of the invention the compositions and methods are used for treatment of benign prostatic hyperplasia. In certain embodiments of the invention the composition comprises a tissue-selective delivery vehicle. In certain embodiments of the invention the compositions comprise an expression vector that encodes a cytotoxic polypeptide, wherein expression of the cytotoxic polypeptide is under control of a prostate-specific regulatory element. In certain embodiments of the invention the compositions comprise an expression vector in which expression of a recombinase is under control of a prostate-specific regulatory element, and a recombination event mediated by the recombinase is required for expression of the cytotoxic polypeptide.

The compositions and methods include targeting peptides selective for tissue selective binding, particularly prostate and / or bone cancer, or adipose tissue. The methods may comprise targeting peptides that bind, for example, cell surface GRP78, IL-11Rα in blood vessels of bone, or prohibitin of adipose vascular tissue. These peptides may be used to induce targeted apoptosis in the presence or absence of at least one pro-apoptotic peptide. Antibodies against such targeting peptides, the targeting peptides, or their mimeotopes may be used for detection, diagnosis and / or staging of a condition, such as prostate cancer or metastatic prostate cancer.

Promoters that include a tissue-selective promoter sequence and a second promoter sequence operatively coupled to the tissue-selective promoter sequence, wherein the second promoter sequence includes a minimal viral promoter sequence, are disclosed. Nucleic acids and compositions that include these promoter sequences are also disclosed. Also disclosed are methods of improving the function of a tissue-selective promoter, involving operatively coupling a tissue-selective promoter sequence with a second promoter sequence that includes a minimal viral promoter sequence. Also disclosed are methods of delivering a gene into a cell, methods of treating a subject with a hyperproliferative disease, and methods of imaging a cell that involve use of the novel promoter sequences set forth herein.

A broad class of photosensitive compounds having enhanced in vivo target tissue selectivity and versatility in photodynamic therapy. Many furocoumarin compounds, such as psoralens, exhibit cytostatic activity when photoactivated but exhibit little in vivo specificity for selectively accumulating in any particular target tissue such as atheromatous plaques. Reactive Oxygen Producing Photosensitizers ("ROPPs") are photoactivatable compounds having an affinity for hyperproliferating cells (such as atheromatous plaque cells), which when photoactivated, produce cytotoxic reaction products. The photoactivity of a ROPP, such as a porphyrin, may be reduced by metalating the porphyrin while the selective affinity of the metalized ROPP for hyperproliferating tissue remains substantially unchanged. By linking a furocoumarin compound to a ROPP to form a F-ROPP, the cytostatic properties of the furocoumarin portion of the F-ROPP can be exploited while the selective affinity of the ROPP portion of the compound for hyperproliferating cells such as atheromatous plaque provides enhanced tissue selectivity without cytotoxicity. In vivo, certain F-ROPPs may be forced to selectively accumulate in a target tissue by illuminating only the target tissue with light having a wavelength operable for photoactivating the F portion of the F-ROPP thereby causing the F-ROPP to either form a monoadduct with or crosslink the cellular DNA in the target tissue. Light of a second wavelength can then be delivered to the target tissue to photoactivate the ROPP portion causing further interference with cellular activity.

A bipolar electrosurgical instrument for clamping, grasping, manipulating, and sealing tissue includes first and second shafts each having a jaw member extending from a distal end thereof and a handle disposed at a proximal end thereof. The handle being operable to effect movement of the jaw members relative to one another from a first position wherein the jaw members are disposed in spaced relation relative to one another to a second position wherein the jaw members cooperate to grasp tissue therebetween. The bipolar instrument is connectable to a source of electrical energy having a first electrical potential connected to one of the jaw members and a second electrical potential connected to the other of the jaw members such that the jaw members are capable of selectively conducting energy though tissue held therebetween to effect a seal. Both the first and second electrical potentials are transmitted to the jaw members through the first shaft.

A surgical method utilizes a cutting blade having a thickness along a cutting edge of between about 0.0005 inch and about 0.020 inch and preferably between about 0.001 inch and 0.010 inch. The blade is moved in contact with relatively hardly tissues which are disposed adjacent to softer tissues at a surgical site in a patient. The blade is ultrasonically vibrated during the moving of the blade, whereby the hard tissue is cut with a modicum of damage being inflicted on the soft tissue.

The invention provides instruments and methods for prophylactic treatment of an osteoporotic vertebral body or for treating a vertebral compression fracture (VCF). In one exemplary method, a probe system uses a high speed rotational cutter for abrading or cutting a plane within vertebral cancellous bone. Optional irrigation and aspiration sources are included in the probe system for removing abraded bone debris. In one embodiment, the high speed cutter uses a tissue-selective abrading surface that abrades or cuts bone but does not cut soft tissue. After the creation of a weakened cut plane in the bone, reduction of the fracture requires reduced forces.

Compounds of formula (I) or (II)wherein Rx, Rz, R9, R10, R14, R14′, R15, R15′, A and B are as defined in the claims and pharmaceutically acceptable salts and esters thereof, are disclosed. The compounds possess utility as tissue-selective androgen receptor modulators (SARM) and are useful as medicaments in the treatment of prostate cancer and other AR dependent conditions and diseases where AR antagonism is desired.

Compounds of structural formula I are modulators of the androgen receptor (AR) in a tissue selective manner. These compounds are useful in the enhancement of weakened muscle tone and the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including osteoporosis, osteopenia, glucocorticoid-induced osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, postmenopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, obesity, aplastic anemia and other hematopoietic disorders, inflammatory arthritis and joint repair, HIV-wasting, prostate cancer, benign prostatic hyperplasia (BPH), abdominal adiposity, metabolic syndrome, type II diabetes, cancer cachexia, Alzheimer's disease, muscular dystrophies, cognitive decline, sexual dysfunction, sleep apnea, depression, premature ovarian failure, and autoimmune disease, alone or in combination with other active agents.

Compounds of structural formula I are modulators of the androgen receptor (AR) in a tissue selective manner. They are useful as agonists of the androgen receptor in bone and / or muscle tissue while antagonizing the AR in the prostate of a male patient or in the uterus of a female patient. These compounds are therefore useful in the enhancement of weakened muscle tone and the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including osteoporosis, osteopenia, glucocorticoid-induced osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, postmenopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, obesity, aplastic anemia and other hematopoietic disorders, inflammatory arthritis and joint repair, HIV-wasting, prostate cancer, cancer cachexia, Alzheimer's disease, muscular dystrophies, cognitive impairment, decreased libido, premature ovarian failure, and autoimmune disease, alone or in combination with other active agents.

Compounds of structural formula I are modulators of the androgen receptor (AR) in a tissue selective manner. They are useful as agonists of the androgen receptor in bone and / or muscle tissue while antagonizing the AR in the prostate of a male patient or in the uterus of a female patient. These compounds are therefore useful in the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including osteoporosis, osteopenia, glucocorticoid-induced osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, postmenopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, obesity, aplastic anemia and other hematopoietic disorders, inflammatory arthritis and joint repair, HIV-wasting, prostate cancer, cancer cachexia, muscular dystrophies, premature ovarian failure, and autoimmune disease, alone or in combination with other active agents.

Compounds of structural formula I are modulators of the androgen receptor (AR) in a tissue selective manner. These compounds are useful in the enhancement of weakened muscle tone and the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including osteoporosis, osteopenia, glucocorticoid-induced osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, postmenopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, obesity, aplastic anemia and other hematopoietic disorders, inflammatory arthritis and joint repair, HIV-wasting, prostate cancer, benign prostatic hyperplasia (BPH), abdominal adiposity, metabolic syndrome, type II diabetes, cancer cachexia, Alzheimer's disease, muscular dystrophies, cognitive decline, sexual dysfunction, sleep apnea, depression, premature ovarian failure, and autoimmune disease, alone or in combination with other active agents.

Compounds for the treatment of estrogen-receptor related maladies are provided. Compounds with anti-androgenic properties also are provided. In particular, the invention provides compounds that are tetrahydroquinoline phenylamide derivatives and are useful for the treatment of breast and prostate cancer, and osteoporosis.

Compounds of structural formula I are modulators of the androgen receptor (AR) in a tissue selective manner. These compounds are useful in the enhancement of weakened muscle tone and the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including osteoporosis, osteopenia, glucocorticoid-induced osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, postmenopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, obesity, aplastic anemia and other hematopoietic disorders, inflammatory arthritis and joint repair, HIV-wasting, prostate cancer, benign prostatic hyperplasia (BPH), abdominal adiposity, metabolic syndrome, type II diabetes, cancer cachexia, Alzheimer's disease, muscular dystrophies, cognitive decline, sexual dysfunction, sleep apnea, depression, premature ovarian failure, and autoimmune disease, alone or in combination with other active agents.

The invention discloses a carbon-controlling and toughening type self-shielded open-arc high-boron surfacing flux-cored wire. According to the technical scheme, a low-carbon-steel H08A cold-rolled thin steel strip is adopted as an outer sheath, and an alloy, graphite and other metal powder are mixed in the sheath to form a powder core, wherein the surfacing alloy is alloy powder obtained by adding high-content ferro-boron, high-carbon ferrochrome and ferrotitanium with different melting properties into the flux-cored wire; by virtue of open-arc surfacing current control, a high-boron surfacing melt with the alloy component in an incompletely-molten and unevenly-mixed state is formed, so that an alloy element phase structure is selectively optimized and configured; the powder core mainly consists of the following components: ferro-boron, high-carbon ferrochrome, ferrotitanium, graphite, medium-carbon ferromanganese, ferrosilicon and reduced iron powder. The carbon-controlling and toughening type self-shielded open-arc high-boron surfacing flux-cored wire overcomes the defect that a current high-boron surfacing alloy is great in brittleness due to microstructure characteristics of the high-boron surfacing alloy, can be widely applied to surfacing manufacturing or repairing of parts with abrasive wear resistance, for example, a concrete cement conveying tube, and is especially suitable for surfacing manufacturing or paring of the parts with low-stress abrasive wear resistance.

A bipolar electrosurgical instrument for clamping, grasping, manipulating, and sealing tissue includes first and second shafts each having a jaw member extending from a distal end thereof and a handle disposed at a proximal end thereof. The handle being operable to effect movement of the jaw members relative to one another from a first position wherein the jaw members are disposed in spaced relation relative to one another to a second position wherein the jaw members cooperate to grasp tissue therebetween. The bipolar instrument is connectable to a source of electrical energy having a first electrical potential connected to one of the jaw members and a second electrical potential connected to the other of the jaw members such that the jaw members are capable of selectively conducting energy though tissue held therebetween to effect a seal. Both the first and second electrical potentials are transmitted to the jaw members through the first shaft.

A surgical method utilizes a cutting blade having a thickness along a cutting edge of between about 0.0005 inch and about 0.020 inch and preferably between about 0.001 inch and 0.010 inch. The blade is moved in contact with relatively hardly tissues which are disposed adjacent to softer tissues at a surgical site in a patient. The blade is ultrasonically vibrated during the moving of the blade, whereby the hard tissue is cut with a modicum of damage being inflicted on the soft tissue.

Compounds of structural formula I are modulators of the androgen receptor (AR) in a tissue selective manner. These compounds are useful in the enhancement of weakened muscle tone and the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including osteoporosis, osteopenia, glucocorticoid-induced osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, postmenopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, obesity, aplastic anemia and other hematopoietic disorders, inflammatory arthritis and joint repair, HIV-wasting, prostate cancer, benign prostatic hyperplasia (BPH), abdominal adiposity, metabolic syndrome, type II diabetes, cancer cachexia, Alzheimer's disease, muscular dystrophies, cognitive decline, sexual dysfunction, sleep apnea, depression, premature ovarian failure, and autoimmune disease, alone or in combination with other active agents.

Compounds of structural formula (I) are disclosed as useful for modulating the androgen receptor (AR) in a tissue selective manner in a patient in need of such modulation, and in particular for antagonizing AR in the prostate of a male patient or in the uterus of a female patient and agonizing AR in bone and / or muscle tissue. These compounds are useful in the treating conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including: osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, female sexual dysfunction, post-menopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, aplastic anemia and other hematopoietic disorders, pancreatic cancer, renal cancer, prostate cancer, arthritis and joint repair, alone or in combination with other active agents. In addition, these compounds are useful as pharmaceutical composition ingredients alone and in combination with other active agents.

Disclosed are nucleic acid sequences encoding a recombinant seven transmembrane G-protein associated receptor (GPCR) amino acid sequence operatively coupled to a tissue-selective promoter sequence. Also disclosed are methods of imaging or treating cells in a subject that involve introducing a nucleic acid encoding a reporter detectable in vivo using non-invasive methods operatively coupled to a tissue-selective promoter or amplified tissue specific promoter to the subject, and subjecting the subject to a non-invasive imaging technique or a therapeutic that selectively interacts with the reporter or gene of interest. For example, the subject may be a subject with cancer, and the therapeutic may be an anti-cancer agent. In particular, the hTERT promoter or amplified hTERT promoter drives expression of a reporter such hSSTR2 and / or hSSTR2 derivative) and these may be linked to a gene of interest. Imaging may be performed by a variety of methods including nuclear medicine.

Compounds of formula (I) wherein R1 to R4, X and A are as defined in the claims and pharmaceutically acceptable salts and esters thereof, are disclosed. The compounds of formula (I) possess utility as tissue-selective androgen receptor modulators (SARM) and are useful in hormonal therapy, e.g., in the treatment or prevention of male hypogonadism and age-related conditions such as andropause.

Compounds of structural formula I are modulators of the androgen receptor (AR) in a tissue selective manner. They are useful as agonists of the androgen receptor in bone and / or muscle tissue while antagonizing the AR in the prostate of a male patient or in the uterus of a female patient. These compounds are therefore useful in the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including osteoporosis, osteopenia, glucocorticoid-induced osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, postmenopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, obesity, aplastic anemia and other hematopoietic disorders, inflammatory arthritis and joint repair, HIV-wasting, prostate cancer, cancer cachexia, muscular dystrophies, premature ovarian failure, and autoimmune disease, alone or in combination with other active agents.

Compounds of structural formula I are modulators of the androgen receptor (AR) in a tissue selective manner. These compounds are useful in the enhancement of weakened muscle tone and the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including osteoporosis, osteopenia, glucocorticoid-induced osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, postmenopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, obesity, aplastic anemia and other hematopoietic disorders, inflammatory arthritis and joint repair, HIV-wasting, prostate cancer, benign prostatic hyperplasia (BPH), abdominal adiposity, metabolic syndrome, type II diabetes, cancer cachexia, Alzheimer's disease, muscular dystrophies, cognitive decline, sexual dysfunction, sleep apnea, depression, premature ovarian failure, and autoimmune disease, alone or in combination with other active agents.

The invention belongs to the technical field of veterinary drugs. The invention discloses a veterinary drug of cefquinome microspheres serving as a lung-targeted preparation prepared by using cefquinome as a raw material and a preparation method thereof. The cefquinome is used as the raw material and gelatin is used as a carrier to form micropheres, and the ratio of the cefquinome to the gelatin is 1:2. The preparation method comprises the following steps: firstly, dissolving the cefquinome in a solution of the gelatin, uniformly mixing the cefquinome and the solution of the gelatin; secondly, dripping the mixed solution in sorbitanmonooleate and liquid paraffin and uniformly stirring the mixture till the mixture turns milky white; quickly cooling the mixture to below 5 DEG C in an ice bath, adding glutaric dialdehyde in form of thin flow, and continuing stirring for cross linking and curing; dehydrating the product obtained with isopropanol, and performing stirring and suction filtration; and washing the dehydrated product with a small amount of isopropanol and ether to remove the glutaric dialdehyde completely, washing away the liquid paraffin on the surface of the microspheres with petroleum ether and drying the microspheres at room temperature and under vacuum to obtain the cefquinome microspheres. The preparation effectively improves tissue selectivity of drug, slows drug release, improves treatment effect, reduces toxic and side effects, and achieves slow release, long-lasting effect and targeting.

The present invention provides a method for screening for progesterone receptor isoform specific ligands as well as a first method for screening for tissue-selective progesterone receptor ligands, both methods comprising selecting progesterone receptor isoform A or progesterone receptor isoform B selective ligands by means of an assay involving cells stably transfected with plasmids expressing the progesterone receptor isoform A or B. Furthermore, the present invention provides a second method for screening for tissue-selective progesterone receptor ligands, comprising in vivo tests in desired target tissues. The present invention further relates to cell lines suitable for this transactivation assay, a respective assay kit and medical uses of the isoform-specific and / or tissue-selective progesterone receptor ligands according to the present invention.

Compounds of formula (I) or (II)wherein Rx, Rz, R9, R10, R14, R14′, R15, R15′, A and B are as defined in the claims and pharmaceutically acceptable salts and esters thereof, are disclosed. The compounds possess utility as tissue-selective androgen receptor modulators (SARM) and are useful as medicaments in the treatment of prostate cancer and other AR dependent conditions and diseases where AR antagonism is desired.