21 results about "Leuprorelin" patented technology

The invention relates to a microflow control preparation method of leuprorelin acetate microspheres, which comprises the following steps: (1) dissolving a hydrophilic-hydrophobic polymer in an organic solvent, adding a leuprorelin acetate aqueous solution, stirring, evaporating and self-assembling for 30 + / -15 minutes to form a W / O type polymer microemulsion; (2) adding the polymer microemulsion into the pregel component, stirring, mixing and volatilizing for 1-2 hours, and removing the organic solvent to form a microgel precursor; and (3) taking the solution in the step (2) as a dispersion phase A, the pre-gel component as a dispersion phase B and fluorinated oil containing 2% of a surfactant Pico-Surf as a continuous phase to be connected into a micro-droplet generation system to generate monodispersed micro-droplets, and performing cross-linking curing, washing out and freeze-drying to obtain the leuprorelin acetate microspheres. The prepared microspheres are uniform in size and good in quality consistency, have the advantages of being high in encapsulation efficiency and drug loading capacity, controllable in drug sustained release, free of obvious burst release and the like, and are more suitable for meeting clinical requirements.

The sustained-release formulation of this invention, with its increased initial release, exhibits a rapid release effect within 24 hours after administration, followed by a sustained-release effect, thus simultaneously achieving both prolonged efficacy and rapid initial release. The sustained-release formulation of this invention, containing microspheres of leuprorelin, possesses excellent bioavailability and has been proven safe in humans; therefore, it can be effectively and safely used to treat various luteinizing hormone-releasing hormone-related diseases such as endometriosis, uterine fibroids, prostate cancer, premenopausal breast cancer, and central precocious puberty.

The invention provides a preparation method of leuprorelin acetate microspheres, and relates to the technical field of drug microspheres. The leuprorelin acetate microspheres are prepared by adopting a W / O / W multiple emulsion method, and the particle size and particle size distribution of the leuprorelin acetate microspheres and the release rate of the leuprorelin acetate are adjusted by reducing the concentration of the leuprorelin acetate in an inner water phase, improving the concentration of polylactic acid in an oil phase and the weight and time of water added in a water supplementing method. Therefore, the leuprorelin acetate microspheres which are high in drug loading content, low in dichloromethane residual rate and stable in drug release are obtained while the loss of leuprorelin acetate is reduced.

This invention belongs to the field of pharmaceutical synthesis, specifically relating to a method for synthesizing leuprorelin impurities. The method uses a specific intermediate, Fmoc-Orn(Pcm)-OH, as a reactant, which not only improves the yield and purity of the synthesized product but also simplifies the synthesis steps, reduces material costs, and is suitable for large-scale industrial production.

Compositions and methods for suppressing ovarian function in subjects with hormone receptor-positive breast cancer.

The invention relates to a 3D printing micro-fluidic chip and a preparation method of leuprorelin acetate sustained-release microspheres, and the preparation method comprises the following steps: preparing a micro-fluidic chip, forming a dispersed phase, a continuous phase and a microsphere runner in the micro-fluidic chip, intersecting the dispersed phase and the continuous phase runner to form a microsphere forming part, and forming a dispersed phase inlet, a continuous phase inlet and a microsphere outlet in the surface of the microsphere forming part; a dispersed phase and a continuous phase are prepared, the dispersed phase comprises an organic solvent, leuprorelin or a salt thereof and a degradable polymer, and the continuous phase is a PVA aqueous solution; respectively injecting the dispersed phase and the continuous phase into a dispersed phase runner and a continuous phase runner according to a set proportion to form leuprorelin acetate droplet microspheres, and solidifying the droplet microspheres after the droplet microspheres flow out from a microsphere outlet to obtain the leuprorelin acetate sustained-release microspheres. According to the preparation method, the particle size uniformity of the leuprorelin acetate sustained-release microspheres can be improved, the drug loading capacity and the encapsulation efficiency of the leuprorelin acetate sustained-release microspheres are improved, the drug release period is prolonged, and the drug utilization efficiency is improved.

Liquid-liquid polymer leuprolide acetate (LA) formulations comprising a biodegradable polymer and biocompatible solvent, and methods of using the formulations.

The invention belongs to the field of drug sustained release preparations, and provides an ovulation inducing preparation for improving fertility and a preparation method thereof. The core-shell structure microsphere design is adopted, leuprorelin acetate is entrapped in the core of the polylactic acid microsphere, and covalently anchored amido bond connection is formed through an end group activated polylactic acid NHS ester intermediate and a chitosan-sodium tripolyphosphate ion network shell layer, so that the high stability of the shell layer is realized; by optimizing the compounding use of the internal phase stabilizer and the freeze-drying protective agent, the particle size distribution D50 of the microspheres is controlled to be 10-60 microns, the thickness of the shell layer is controlled to be 0.05-5 microns, and high encapsulation efficiency, good drug slow release performance and excellent storage stability are realized. The technical problems that in an existing peptide medicine core-shell microsphere system, a shell layer is prone to falling off, the medicine is suddenly released, and the stability is poor after freeze-drying are solved, and the peptide medicine core-shell microsphere has the advantages of being high in encapsulation efficiency, controllable in release and good in biocompatibility and has wide application value in the technical field of assisted reproduction.

The invention relates to the technical field of leuprorelin synthesis, in particular to a solid-liquid synthesis process of high-purity leuprorelin, Fmoc-Arg (Pbf)-OH, Fmoc-Tyr (tBu)-OH and 2-CTC resin are used as initial raw materials, and a leuprorelin crude product solid is obtained through a series of treatment such as deprotection, condensation, cutting, fragment docking, C-terminal dipeptide condensation and cracking. Compared with the prior art, the method has the remarkable advantages of simplicity and convenience in operation, low raw material investment, short production period, low cost and the like, meanwhile, the product synthesis yield is high (can reach 85%), the environmental pollution is small, industrial production is easy to realize, and the method has a wide market application prospect.

The invention discloses a synthetic method of leuprorelin, and relates to the technical field of pharmaceutical processes. The invention provides a method for synthesizing leuprorelin, which comprises the following steps of: performing solid-phase synthesis on a Pyr1-His2 (Trt)-Trp3 (Boc)-Ser4 (tBu)-Tyr5 (tBu)-D-Leu6-OH fragment, performing liquid-phase synthesis on an NH2-Leuu-Arg (pbf)-Pro-NHEt fragment, coupling the two obtained fragments to obtain a leuprorelin full-protection peptide, and performing splitting decomposition, precipitation and purification to obtain a pure leuprorelin product.

The present technology relates to multi-dose injection pens, pharmaceutical compositions of leuprolide and combinations thereof. The multi-dose injection pens may be configured to contain multiple doses of leuprolide and to administer a single dose of leuprolide.

A liquid-liquid polymer leuprorelin acetate (LA) formulation comprising a biodegradable polymer and a biocompatible solvent, and methods of using the formulation.

The invention relates to a sustained release microsphere containing high-content leuprorelin, an injection preparation containing the sustained release microsphere and a preparation method of the sustained release microsphere. According to the present invention, during administration, leuprorelin is released at an early stage at a sufficient level to exhibit the effect of leuprorelin, thereby allowing exposure to a sufficient amount of a drug while minimizing an inflammatory response or the like that may be a problem at the time of administration, and thus the effect of leuprorelin can be safely exhibited for at least one month.

The present invention discloses a preparation method of a leuprorelin-related compound. In this method, 2-chlorotrityl chloride resin (2-CTC resin) is used as a solid-phase carrier, which is coupled with an amino acid to prepare fragment one; then it is coupled with an amine compound to obtain fragment two, and then the side-chain protecting groups of fragment two are removed by cleavage with trifluoroacetic acid, and the leuprorelin-related compound is purified. The reaction operation of the present invention is simple, the post-treatment is convenient, the yield is high, and it has high reference value for leuprorelin. Moreover, through the preparation of the leuprorelin-related compound, the present invention provides an important basis for the scientific evaluation of the efficacy, pharmacological research, pharmacokinetics, etc. of leuprorelin, facilitating more in-depth research on its metabolic process and pharmacokinetics in the human body, and endowing it with better medicinal prospects.

The present application discloses Lactobacillus reuteri and its application in relieving perimenstrual syndrome, and relates to the technical field of biology. Limosilactobacillus reuteri ​ Lactobacillus reuteri (Lactobacillus reuteri) -NCU-37 was preserved in China General Microbiological Culture Collection Center on February 24, 2025, and the address is No. 1, Xibaixili, Chaoyang District, Beijing, and the preservation number is CGMCC NO. 33627. The Lactobacillus reuteri -NCU-37 of the present application can relieve perimenstrual syndrome induced by leuprolide in assisted reproductive treatment, specifically relieve perimenstrual syndrome and related emotional disorders (including anxiety, depression and insomnia), improve the hormone level of infertile women with perimenstrual syndrome, and relieve the symptoms of infertile women with perimenstrual syndrome by regulating intestinal flora diversity.

The invention discloses lactobacillus reuteri and application thereof in relieving perimenopausal syndrome, and relates to the technical field of biology. The lactobacillus reuteri NCU-37 is preserved in the China General Microbiological Culture Collection Center (CGMCC) on February 24, 2025, the address is No.3, No.1 yard, Beichen West Road, Chaoyang District, Beijing, and the preservation number is CGMCC NO.33627. The lactobacillus reuteri NCU-37 has the advantages that the lactobacillus reuteri NCU-37 can be used for preparing the lactobacillus reuteri NCU-37, and the lactobacillus reuteri NCU-37 can be used for preparing the lactobacillus reuteri NCU-37; the lactobacillus reuteri-NCU-37 can relieve perimenopausal syndromes induced by leuprorelin in assisted reproduction therapy, particularly relieve the perimenopausal syndromes and related emotional disorders (including anxiety, depression and insomnia), improve the hormone level of infertility women accompanied with the perimenopausal syndromes, improve the curative effect of the perimenopausal syndromes and improve the curative effect of the perimenopausal syndromes. And the symptoms of infertility women accompanied with the perimenopausal syndrome are relieved by adjusting the diversity of intestinal flora.

Compositions and methods for suppressing ovarian function in subjects with hormone receptor-positive breast cancer.

The present technology relates to multi-dose injection pens, pharmaceutical compositions of leuprolide and combinations thereof. The multi-dose injection pens may be configured to contain multiple doses of leuprolide and to administer a single dose of leuprolide.

The invention belongs to the technical field of preparation of leuprorelin, and particularly relates to an improved leuprorelin sustained release microsphere and a preparation method of the improved leuprorelin sustained release microsphere. Comprising the following components: 10-15 parts of leuprorelin, 60-80 parts of a polylactic acid-glycolic acid copolymer, 3-6 parts of an amino-containing hydrophilic modifier, 1-3 parts of a water-soluble stabilizer, 2-4 parts of a buffer agent and 0.6-1.2 parts of an emulsifier. Wherein the molar ratio of lactic acid to glycolic acid in the polylactic acid-glycolic acid copolymer is (1-3): 1, and the viscosity average molecular weight of the polylactic acid-glycolic acid copolymer is 30000-80000Da. The amino-containing hydrophilic modifier and the polylactic acid-glycolic acid copolymer form a synergistic effect, so that the hydrophobicity of the sustained-release microsphere is remarkably reduced, a core-shell structure is formed, and the release period of leuprorelin is further prolonged.

The sustained release formulation with an increased initial release amount according to the present invention exhibits a rapid release effect within 24 hours after administration and can exhibit a continuous sustained release effect thereafter, thereby achieving long-term drug efficacy persistence and an initial rapid release purpose at the same time. Found to have excellent bioavailability and be safe in the human body, the sustained-release formulation comprising microspheres containing leuprorelin according to the present invention thus can be effectively and safely used for the treatment of various luteinizing hormone-releasing hormone-related diseases such as endometriosis, uterine myoma, prostate cancer, pulmonary pre-menopausal cancer, and central precocious puberty.