99 results about "Bone targeting" patented technology

The invention relates to an exosome carrier of a targeted bone, a CRISPR / Cas9 gene editing system and application. The exosome carrier comprises a targeted peptide of any one of a targeted bone forming surface, a bone absorbing surface and an endothelial cell. The exosome carrier can be fused with (AspSerSer)6, (Asp)8 and a CREDVW oligopeptide respectively by transforming an exosome surface membrane protein lamp2b, so that an exosome can be fused with the targeted bone forming surface, the bone absorbing surface and the endothelial cell. Therefore, the bone targeting exosome is developed as the carrier, a CRISPR / Cas9 system serves as a gene editing and controlling tool, and the two parts are combined to play the important significance on the treatment of various bone diseases.

The present invention provides bone-targeting polymeric drug delivery systems based on HPMA and related copolymers and methods of making thereof. The water-soluble bone-targeting polymeric conjugates of the present invention comprise water-soluble copolymer backbones (P) which are linked, via a first spacer (S1), with a bone-related therapeutic agents or drug (D) and, via a second spacer (S2), with a bone-targeting moiety (T).

This invention provides a method of modifying a cellular response in a mammal. The method comprises administering to the mammal an effective amount of biodegradable nanoparticles, each of said nanoparticles comprising an active agent, a biodegradable polymer, and a bone targeting agent administering to a mammal an effective amount of a composition comprising a compound absorbed in a biodegradable nanoparticle which is attached to a bone targeting agent. The invention also provides a method for modifying a cellular response in a mammalian cell comprising contacting the mammalian cell with biodegradable nanoparticles. The invention further provides a method of delivering an exogenous substance to a mammal. The method comprises administering to the mammal a composition comprising the exogenous substance absorbed into a biodegradable nanoparticle, wherein the biodegradable nanoparticle is covalently attached to a bone targeting agent. The invention also provides a composition and a process for preparing the composition comprising a biologically active or therapeutic agent of compound, a biodegradable nanoparticle, and a bone targeting agent.

Conjugates of polymers or copolymers having attached thereto an anti-angiogenesis agent and a bisphosphonate bone targeting agent, and processes of preparing same, are disclosed.Pharmaceutical compositions containing these conjugates and uses thereof in the treatment of bone related disorders are also disclosed.

Methods of using Th-226 or mother radionuclides thereof, namely U-230 or Th-226, in medicine. These radionuclides are particularly appropriate for the treatment of human and / or non-human mammals, in particular for therapeutic, diagnostic (detection / imaging), prophylactic and pain palliation purposes. These radionuclides may be used in various forms for treatment and / or diagnostic purposes, in particular in cationic form or in the form of radioconjugates or bone-targeting complexes. Methods of making such radionuclides.

The present invention relates to compounds of the formulaor pharmaceutically acceptable salts thereof, useful for delivering agents having the capacity to diagnose, treat or prevent bone injury or disease to the bone for interaction therewith.

Polymeric conjugates comprising a polymeric backbone having attached thereto a bone targeting moiety and a therapeutically active agent, wherein the bone targeting moiety is attached to one end of the polymeric backbone via a branching unit such that a molar ratio of the bone targeting moiety to the polymer is at least 2:1, are disclosed. Pharmaceutical compositions containing these conjugates and uses thereof in the treatment of bone related disorders are also disclosed.

The invention discloses a bone-targeted anti-inflammatory agent, a synthesis method and application thereof, and in particular relates to compounds having a structure in a formula (II), wherein R1 or R2 respectively independently refers to hydrogen or acyl between C1 and C8; R3 refers to aspirin, ibuprofen, naproxen, indometacin or carboxyl residue of diclofenac; and n refers to an integer between 1 and 10. The application of the compounds is to prepare the bone-targeted antiinflammatory agent, in particular medicines for treating osteoarthritis or rheumatic arthritis.

The invention discloses a tanshinol lipidosome bone-targeting pharmaceutical preparation and a preparation method thereof. The preparation is prepared by jointing and carrying out surface modification on a lipidosome microparticle containing a tanshinol medicine molecule by using a bone-targeting jointer. The preparation method comprises the steps of jointing a bisphosphonate molecule with bone-targeting ability on one end of a polyethylene glycol molecule through synthetic reaction, and jointing a cholesterol molecule serving as a lipidosome raw material on the other end of the polyethylene glycol molecule through synthetic reaction to prepare a jointer with bone-targeting ability, namely bisphosphonate-polyethylene glycol-cholesterol (BP-PEG-CHOL); and then, preparing a lipidosome provided with the bone-targeting jointer on the surface from phospholipid, cholesterol and the bone-targeting jointer which serve as raw materials, adding tanshinol, and containing the tanshinol into the lipidosome to prepare the tanshinol lipidosome bone-targeting preparation. The preparation disclosed by the invention has the bone-targeting ability and can be used for remarkably increasing the concentration of medicines in a bone tissue, improving the curative effect and preventing and treating systemic metabolic bone diseases, osteoporosis and bone fracture.

Polymeric conjugates comprising a polymeric backbone having attached thereto a bone targeting moiety and a therapeutically active agent, wherein the bone targeting moiety is attached to one end of the polymeric backbone via a branching unit such that a molar ratio of the bone targeting moiety to the polymer is at least 2:1, are disclosed. Pharmaceutical compositions containing these conjugates and uses thereof in the treatment of bone related disorders are also disclosed.

The invention provides a stearic acid grafted tetracycline. A stearic acid grafted tetracycline is mixed with a lipid material for preparing a bone targeted lipid nanometer carrier; the bone affinity capability is realized; the bone targeting effect is achieved; the lipid material can more easily coat statin medicine. The stearic acid grafted tetracycline provided by the invention has the good affinity; the bone affinity is higher when the proportion of the stearic acid grafted tetracycline is higher; the stearic acid grafted tetracycline can be used for bone targeted carrier building; the prepared bone targeted nanometer carrier can also be used for oral administration. The structural formula of the stearic acid grafted tetracycline is shown as the accompanying description.

Polymeric conjugates comprising a polymeric backbone having attached thereto a bone targeting moiety and a therapeutically active agent, wherein the bone targeting moiety is attached to one end of the polymeric backbone via a branching unit such that a molar ratio of the bone targeting moiety to the polymer is at least 2:1, are disclosed. Pharmaceutical compositions containing these conjugates and uses thereof in the treatment of bone related disorders are also disclosed.

Conjugates of polymers or copolymers having attached thereto an anti-angiogenesis agent and a bisphosphonate bone targeting agent, and processes of preparing same, are disclosed.Pharmaceutical compositions containing these conjugates and uses thereof in the treatment of bone related disorders are also disclosed.

The invention provides a bone targeting gene carrier. The bone targeting gene carrier is a lipidosome modified by alendronate sodium, wherein the lipidosome modified by alendronate sodium comprises cationic lipid, neutral auxiliary lipoid, cholesterol and phospholipid modified by alendronate sodium, the cationic lipid, the neutral auxiliary lipoid and the cholesterol form a phospholipid layer, the phospholipid modified by alendronate sodium is distributed in the phospholipid layer and forms a vesica structure with the phospholipid layer, and alendronate sodium is exposed out of the phospholipid layer. The bone targeting gene carrier has relatively high targeting property and transfection efficiency for the bone tissue, and can be efficiently expressed near the bone tissue by being loaded with a gene substance. The invention further provides a preparation method and applications of the bone targeting gene carrier.

The instant invention relates to compositions and methods for treating or preventing bone diseases. In certain aspects, the invention provides compositions comprising a β-adrenergic antagonist or agonist associated to a bone-targeted molecule, as well as methods of modulating bone mass and / or growth in a mammal by administering a composition of the present invention. In other aspects, the invention provides methods of modulating bone mass and / or growth in a mammal by administering a composition comprising a β2-selective antagonist or agonist.

Methods and solutions are describes whereby radiopharmaceutical radium-224 solutions are added complex for scavenging daughter nuclide, which may enhance the overall targeting and reduces uptake of daughter nuclide in normal tissues and cells. This is accomplished without reducing the bone targeting ability of radium. The methods and solutions are convenient to use since the complexation of daughter nuclide can be done in situ in a ready to use radiopharmaceutical solution or, depending on the activity concentration, in a simple kit format by mixing two solutions and store the mixture for typically 1 minute to a few hours before administration to a patient. The use of targeted chelate scavengers for 224Ra daughter nuclide opens up the possibility for using 224Ra based solutions for medical treatments.

The invention discloses a polypeptide for treating osteoporosis, wherein the amino acid sequence is (Asp-Ser-Ser)6-(D-Tyr)-Asn-(D-Trp)-Asn-Ser-Phe-(azaGly)-Leu-Arg(Me)-Phe-NH2((AspSerSer)6-Kp-10, SEQID NO:1). The present invention further discloses a preparation method of the polypeptide, wherein the preparation method comprises: polypeptide synthesis, polypeptide cleavage, and separation and purification of the crude polypeptide. The invention further relates to applications of the polypeptide in preparation of drugs for treatment of osteoporosis. According to the present invention, the research results prove that the knockout of the Gpr54 or Kiss1 gene can cause osteoporosis and excessive activation of osteoclasts, Kp-10 inhibits osteoclast differentiation, actin-ring formation and boneresorption by activating Gpr54, and (AspSerSer)6-Kp-10 has good bone targeting effect and cab effectively treat ovariectomy induced osteoporosis in vivo compared to Kp-10, such that the theoretical basis is provided for the treatment of osteoclast-related diseases.

The invention discloses a bone-targeting hypoxic response nano-micelle loaded with an anti-cancer drug and a preparation method thereof. The preparation method disclosed by the invention comprises thefollowing steps: carrying out copolymerization reaction on polyethylene glycol and a low-oxygen response group (4, 4-diaminoazobenzene) to obtain carboxyl polyethylene glycol azobenzene; carrying outring-opening polymerization reaction on the carboxyl polyethylene glycol azobenzene and N-carbobenzoxy-L-lysine-N-carboxylic anhydride to obtain a polyethylene glycol-polylysine segmented copolymer with carbobenzoxy on the surface, and removing the carbobenzoxy to obtain a polyethylene glycol-polylysine segmented copolymer; carrying out copolymerization reaction on the polyethylene glycol-polylysine segmented copolymer and a bone-targeting group (alendronate) to obtain a bone-targeting hypoxic response polymer; and synthesizing the bone-targeting hypoxic response nano-micelle loaded with theanti-cancer drug by a dialysis method. The nano-micelle prepared by the preparation method disclosed by the invention is stable in structure and not easy to decompose, has a targeting effect on bone tissues, and can also play a role in low-oxygen controlled release of drugs.

The invention provides a preparation method and application of a bone-targeted RNA interference compound. The RNA interference compound comprises siRNA and (D-Asp8)-(STR-R8) carriers. Specifically, the preparation method comprises the following steps: coupling bone-oriented D-Asp8 (oligopeptide of a bone tissue-targeted water-soluble polymeric drug carrier) and STR-R8 cationic polymer (a good gene transfection carrier) by adopting a chemical method, and attracting and packaging siRNAs aiming at target genes to STR-R8 through heterogeneous charge to obtain the bone-targeted drug. The bone-targeted drug directionally acts on bone tissues under the guide effect of D-Asp8, and achieves different effects by carrying corresponding siRNAs aiming at different target genes. According to the preparation method and application of the bone-targeted RNA interference compound, the application range is wide, the bone affinity is good, the synthetic steps are simple, and the conditions are easy to control.

The invention provides a bone-targeting drug delivery system based on near-infrared II quantum dots as well as a preparation method and application thereof. The drug delivery system comprises near-infrared II quantum dots, and the surfaces of the near-infrared II quantum dots are modified by amino polyethylene glycol. The grain size of the near-infrared II quantum dots of the bone-targeting drug delivery system is less than 20nm, and therefore the near-infrared II quantum dots can pass through the blood-marrow barrier to arrive at bone tissues. Since the surfaces of the near-infrared II quantum dots are modified by amino polyethylene glycol, the near-infrared II quantum dots are electropositive, and therefore can be efficiently combined with electronegative hydroxyapatite in bones throughthe action of electrostatic force. The quantum dots only depend on the physical effect to be attached onto the bone tissues by means of kinetics and electrostatic force, achieving the bone-targeting effect, the quantum dots cannot interfere with the therapeutic effect of a drug, and the side effect is minor. Since the carrier is provided with the near-infrared II fluorescent quantum dots, the bone-targeting drug delivery system can track the whole bone targeting process by means of near-infrared II fluorescent signals, which is favorable for the pharmacological research of drugs.

The invention discloses glutathione sensitive bone targeted liposome and a preparation method thereof. The bone targeted liposome is prepared by modifying amphipathic materials of alendronate-hyaluronic acid-aminiform-cholesterol on a phosphatide dimolecular layer framework of liposome. The glutathione sensitive bone targeted liposome disclosed by the invention is prepared by modifying a glutathione sensitive bone targeted material to the liposome, so that bone tissue can be targeted, besides, disulfide bonds can be embedded into the liposome and can be rapidly cracked in tumor cells rich in glutathione, and medicines can be released out.

The invention discloses a bone targeting medicinal vector and medicament. The bone targeting medicament vector is prepared by the following steps of: oxidizing glucan into glucan oxide containing a poly-aldehyde group with sodium periodate; and making diphosphonic acid containing an amino group react with the glucan oxide containing the poly-aldehyde group. The medicament with a bone targeting property is obtained by the following steps of: making the bone targeting medicament vector react with a medicament containing an amino group; and connecting the glucan oxide containing the poly-aldehyde group serving as an intermediate with diphosphonic acid with a bone guiding function and other medicaments (except diphosphonic acid) containing amino groups, wherein the prepared bone targeting medicament has high bone affinity and large medicament loading capacity when the reaction mass ratio of the diphosphonic acid to the glucan oxide aldehyde group is (0.4-0.6):1. The bone targeting medicament acts on bone tissues in an oriented way under the guiding action of the diphosphonic acid, and has different treating effects by loading different medicaments. The bone targeting medicament has the advantages of large medicament loading capacity, high bone affinity, simple synthesizing steps and easiness for controlling conditions.

The invention discloses a bone targeted liposome containing a compound of a structure in Formula 5, wherein n is selected from integers from 1 to 100, and the invention also discloses a bone targeted liposome drug containing the liposome and active drug molecules wrapped therein and preparations of the bone targeted liposome drug and a preparation method and application thereof. The bone targeted liposome uses pyrophosphoric acid to modify the liposome surface, has good bone affinity and good targeting, solves the problem that bonding between existing bone targeted drugs and a bone surface is insufficient, and can be targeted to various surfaces of bones: a bone absorption surface, a bone forming surface, a bone growth plate, the interior of cortical bone and a bone concave cavity, a bone targeting characteristic range is wider, and requirements for loading various drugs for treating bone diseases can be fully satisfied. The invention also discloses a tanshinol bone targeted liposome drug and application thereof in fracture healing disorders, and the drugs can promote formation of callus in an early stage, and promote transformation of the callus to normal bone in a later stage, thereby remarkably shortening fracture healing time and enhancing the mechanical property of bone after fracture healing.

The invention provides a method of inhibiting cell death in a mammal. The method comprises administering to a mammal an effective amount of a composition comprising a cell protection factor covalently linked to a bone targeting agent via a linkage that is cleaved under physiological conditions, whereby the cell protection factor is released from the bone targeting agent in vivo to inhibit cell death. The invention further provides a compound comprising a cell protection factor covalently attached to a bone targeting agent via a linker that is cleaved under physiological conditions.

Methods and solutions are describes whereby radiopharmaceutical radium-224 solutions are added complex for scavenging daughter nuclide, which may enhance the overall targeting and reduces uptake of daughter nuclide in normal tissues and cells. This is accomplished without reducing the bone targeting ability of radium. The methods and solutions are convenient to use since the complexation of daughter nuclide can be done in situ in a ready to use radiopharmaceutical solution or, depending on the activity concentration, in a simple kit format by mixing two solutions and store the mixture for typically 1 minute to a few hours before administration to a patient. The use of targeted chelate scavengers for 224Ra daughter nuclide opens up the possibility for using 224Ra based solutions for medical treatments.

The invention relates to a calcium-affinity nanoparticle with Pamidronate disodium-modified Brij78 as a key component and a preparation method thereof. The key component is a surfactant with a calcium affinity effect and is prepared by reacting a series of Brij compounds with p-methyl benzene sulfonic chloride to prepare an intermediate and then reacting the intermediate with bisphosphonate. According to the invention, good surface activity of the series of Brij compounds is retained, and calcium affinity capability of the series of Brij compounds is improved at the same time. The preparation method has the advantages of reliable principles, simple steps, easy operation, high security of used reactants and solvents and small pollution to the environment. The Pamidronate disodium-modified Brij78 has good high temperature stability and chemical stability; and a variety of drug-loaded nanoparticles prepared from the Pamidronate disodium-modified Brij78 have calcium affinity and bone targeting performances and can be used in the technical field of medicine.

The invention relates to a nano material and application thereof, in particular to a bone targeting nano material. The bone targeting nano material comprises catalpol, alendronate sodium, polyethyleneglycol and a poly (lactic-co-glycolic acid) copolymer. TEM (transmission electron microscope) detection and diabetes mouse osteoporosis model pharmacodynamic experiments prove that the material can be better distributed in bone tissue, has a remarkable treatment effect, and has good open prospect.

The invention discloses a cholesterol pyrophosphate, and a preparation method and a use thereof. Cholesterol and pyrophosphate are connected through click chemistry, and the targeting auxiliary material cholesterol pyrophosphate (PPi-Chol) having strong affinity to bones is prepared through combining the wide application of the cholesterol in a medicinal preparation with the bone targeting property of the pyrophosphate, so the studying process of the bone targeting dosage form is greatly improved, and the therapy effect of bone related diseases is improved.

The invention discloses a nano material for an osteoclast acidic closed region and a preparation method thereof. The nano material for the osteoclast acidic closed region comprises a nano material, bone targeting molecules and a compound which generates a chemical reaction on the osteoclast acidic closed region, after the nano material is subjected to bone targeting molecular modification, a compound which generates a chemical reaction on an osteoclast acidic region is entrapped; according to the nano material, osteoclasts are inhibited through accurate mature osteoclast targeting and physiological chemical reaction regulated biological cascade reaction, and a new thought and a new tool are provided for pharmaceutical treatment of osteoclast abnormal activation.