66 results about "Leuprorelin" patented technology

The invention discloses a bright-ala-ruilin preparing method of solid-phase polypeptide, which comprises the following steps: adopting Wang resin or CTC resin as original material to connect amino with protective group to produce protective nonapeptide resin; removing Fmoc-protective group sequently; proceeding side-chain protective group synchronizingly and cutting peptide; connecting ethylamine through ethylamine-to-HOBT to produce crude product; proceeding separation and purifying through C18 (or C8) pillar to produce fine bright-ala-ruilin. The invention avoids the utility of poisonous agent, which improves the purifying, peptide connecting and obtaining rate.

The invention relates to a solid phase synthesis method of leuprorelin, which uses 4-((1-N-Alkylamino)ethyl) phenoxy-butyramide resin as a solid phase carrier to carry out procedure reaction, and peptide whole protecting resin can be obtained by sequentially carrying out condensation reaction to connect protecting amino-acid; crude peptide can be obtained by cutting the resin by trifluoroacetic acid, and the crude peptide is dissolved in an acetic acid water solution of 5 percent, and the leuprorelin can be obtained by purifying, leaching, condensing and freeze drying the opposite phase high performance liquid chromatograph columns of C18 fillers. The invention uses a novel solid phase resin, and products decorated by peptide chain carbon end alkyl can be obtained directly after finishing assembling the peptide chain by the solid phase synthesis technology and using acid hydrolysis to cut the peptide from the resin after, and the solid phase synthesis method of the leuprorelin is convenient in operation, reduces synthesis steps for synthesizing the leuprorelin greatly and improves the yield.

The invention relates to a leuprolide acetate preparing method to mainly solve the technical problems of existing leuprolide acetate preparing methods that the production process is complicated, the period is long, the cost is high, the yield is low, and salt conversion is difficult.According to the technical scheme, a leuprorelin crude product is obtained through solid-phase synthesis, the leuprorelin crude product is dissolved, filtered and detected, and then coarse purification, fine purification, concentration, salt conversion, recondensation and filtration are conducted on the leuprorelin crude product by means of an invert high liquid-phase chromatographic system, and finally freeze drying is conducted to obtain a white flocculent powdery product.The purification preparing method is suitable for laboratory research and development as well as large-scale industrial production.

The invention discloses an insoluble leuprorelin sustained-release preparation.Leuprorelin acetate is prepared into insoluble salt firstly, then emulsification is carried out through a single emulsion method, and leuprorelin microspheres are prepared through an in-liquid drying technology.The production process is simplified, there are few pores in the surfaces of the microspheres, the drug encapsulation rate is high, the product yield is high, and drug burst release is remarkably lowered.

The invention discloses a leuprorelin synthesis method. According to the method, a dipeptide midbody is obtained through liquid-phase synthesis and then used for solid-phase synthesis to generate full-protection nonapeptide peptide resin, full-protection nonapeptide is cut off from the resin and then inoculated with ethylamine in the liquid phase to generate full-protection leuprorelin, and a leuprorelin crude product is obtained through splitting decomposition. The method specifically comprises the steps of obtaining Fmoc-Leu-OSU fat through condensation under the action of a condensing agent; reacting with H-Arg(pbf)-OH under the action of alkali to generate Fmoc-Leu-Arg(pbf)-OH; obtaining Fmoc-Pro-CTC Resin through reaction under the action of the alkali; removing Fmoc, and conducting amino acid coupling in sequence under the action of a condensing agent to generate full-protection nonapeptide peptide resin; cutting the full-protection nonapeptide peptide resin with a cutting reagent to generate full-protection nonapeptide; generating leuprorelin full-protection peptide by means of full-protection nonapeptide and ethylamine hydrochloride under the action of a condensing agent, and obtaining the leuprorelin crude product through splitting decomposition. By the adoption of the method, the yield and purity of leuprorelin are improved remarkably, ammonolysis is not needed, and reaction is easy and controllable. The method is suitable for industrial production.

The invention relates to synthesis of leuprorelin, in particular to a method for synthesizing leuprorelin by a solid phase and a liquid phase, and mainly solves the technical problem that as tryptophan serine fragments in the conventional leuprorelin synthesis process has the probability of secondary conformation changes, the molecular activity is influenced to result in low yield of HPLC chromatography purification products. The method comprises the following steps: (1) enabling reaction between Fmoc-Pro-OH and 2-chlorotrityl choloride resin with the substitution degree of 0.4-0.6 mmol to produce Fmoc-Pro-resin; (2) sequentially coupling amino acids to form a solid-phase polypeptide; (3) cutting to obtain an all-protected polypeptide sequence; (4) performing liquid-phase condensation on all-protected polypeptides and ethylamine, closing the polypeptide carboxyl terminal, and performing side chain removal protection to obtain a leuprorelin crude peptide; (5) adopting efficient counter-current chromatography extraction, and then freeze-drying to obtain leuprorelin pure peptide.

The invention relates to a synthesis method of leuprorelin, which can resolve the problems that prior art uses solid-phase synthesis which cuts leuprorelin from resin unsafely, and has long liquid phase synthesis time. The invention comprises a, solid-phase synthesizing whole-protected peptide chain PGIuR-8, b, synthesizing material Pro-NHEt. HCI, c, condensing liquid-phase fractions to synthesize whole-protected PGIuP-9-NHEt via using DIC or BOP to react for 24-36h at 10-30DEG C, d, removing protection to obtain crude leuprorelin. The invention can synthesize polypeptide whose C end is amide.

The invention discloses a leuprorelin synthesis preparation method. The method comprises the following steps: using a chloride resin as a starting resin carrier, dissolving mercaptoethylamine with alkaline solvent, mixing with the chloride resin under a homothermal condition, and reacting over night to obtain an ethylamine chloride resin; adding methanol and DIEA (diisopropylethylamine) having equal volume ratios into the ethylamine chloride resin, and performing end-capping reaction; washing the end-capped ethylamine chloride resin with DMF (N,N-dimethylformamide), sequentially putting activated Fmoc protective amino acid into a reaction vessel, and performing continuous peptide chain condensation reaction; treating the reactive chloride resin by means of a microwave technique, and washing the peptide chain-chloride resin obtained after the reaction with a DMF solution; and performing cleavage reaction on the fully-protected leuprorelin-chloride resin by means of a cleavage reagent to obtain a leuprorelin crude peptide, and then purifying through reversed-phase high-performance liquid chromatography. The method disclosed by the invention greatly simplifies the process flow, shortens the production time, lowers the production cost, and improves the reaction condensation efficiency and pure product yield, thereby having considerable market competitiveness and application prospects.

The invention provides a leuprorelin slow-controlled drug release stick and a preparation method thereof. The preparation method comprises the following steps of mixing raw leuprorelin, high molecular weight type resin and low molecular weight type resin to obtain a solution or suspension; drying the solution in a vacuum manner; evaporating to remove a solvent to obtain a solid; pressing the solid to obtain a drug stick. The preparation method provided by the invention is simple in process and preparation is easy to carry out; the prepared leuprorelin stick is innocuous and unpoisonous to a human body, has no side effect, and is high in curative effect and is small in dose.

An anticarcinogenic slow release formulation carrying an anticancer drug and a synergist is a slow release injection or a slow release implant, and the slow release injection is made from slow release microspheres and a dissolvant. The slow release microspheres comprise anticancer active components and a slow adjuvant, and the dissolvant is a special dissolvant containing a suspending agent which is selected from sodium carboxymethyl cellulose and the like, and the viscosity of the suspending agent is 80cp-3,000cp (at room temperature). The anticancer active components are alkylating agents such as melphalan, ifosfamide and the like, purine analogues such as O6-BG and the like, and/or hormones anticancer drugs selected from triptorelin, goserelin, leuprorelin and a composition selected from epothilone (A-F) and derivatives thereof; the slow release adjuvant is chosen from one of or the copolymer or the mixture of polylactic acid and a copolymer thereof, polifeprosan and the copolymer or the mixture of polylactic acid and sebacic acid copolymer; the slow release implant and the slow release injection are injected or put in tumors or around the tumors, which is beneficial to diffusing the drug in the solid tumors, maintaining high concentration, reducing drug tolerance, being capable of mutual synergy and enhancing curative effects of chemotherapy and/or radiotherapy.

The invention relates to a temperature-controlled sustained-release injection containing a hormone anti-cancer drug, which comprises the anti-cancer drug, an amphiphilic block copolymer, a solvent and a certain amount of drug release regulator, wherein, the mixture of the amphiphilic block copolymer and a solvent without organic solvent has the temperature-sensitive gelatinization feature, which is flowable liquid in the environment that is lower than the body temperature and can be automatically converted to the water-insoluble gel that can not flow and be biodegradable for absorption in an endotherm, and the water-insoluble gel can allow the contained hormone anti-cancer drug to have the local sustained release in a tumor and maintain the effective drug concentration for a plurality of weeks to a plurality of months; the viscosity of the temperature-controlled sustained-release injection is 10cp to 3000cp ( at 5 DEG C to 30 DEG C ), and the gelatinization temperature is 35 DEG C to 37 DEG C. The sustained-release injection can be injected in the tumor or the tumor periphery or be arranged in the postoperative tumor cavity, thus significantly reducing the systemic reaction of the drug, selectively strengthening the treatment effects of chemotherapy, radiotherapy and other non-surgical therapies, and being used for the treatment of the tumors in different stages. The anti-cancer drug can be triptorelin, goserelin, leuprorelin, anastrozole, idoxifene, tamoxifen and other hormone anti-cancer drugs.

The invention relates to a leuprorelin medicinal composition injection type hypodermic implantation agent. The leuprorelin medicinal composition injection type hypodermic implantation agent is characterized in that medicine active ingredients are leuprorelin, plant extract and hormone or resistance hormone active medicine cooperating with leuprorelin; in addition, an implantation agent is injected subcutaneously in a liquid mode, under the effect of the body temperature, the solution is changed into gel, and then the effect of controlled release of multiple sex hormone dependent diseases is exerted. Through the implantation agent prepared through the method, on the one hand, the use amount is reduced while the medicine effect is kept, toxic and side effects are reduced, and medicine use safety and compliance are improved; on the other hand, the medicine is slowly released in the body, and the long-acting effect of treating the sex hormone dependent diseases is achieved.

The invention provides a PEG-leuprorelin conjugate and a preparation method thereof. The preparation method is characterized in that: firstly PEG is connected with maleic anhydride for forming an active ester, the PEG modification agent is connected to leuprorelin with protection by Mal, and then a de-protection is carried out to obtain a PEG-leuprorelin conjugate with a single site modification. The compound has the original activity of leuprorelin, and simultaneously has a longer half life and a longer average peak time.