Institute of Microbiology, Chinese Academy of Sciences (Chine)
Hybio Pharmaceutical Co., Ltd. (Chine)
Inventeur(s)
Gao, Fu
Zeng, Shaogui
Wang, Qihui
Tang, Yangming
Chen, Jiantao
Wu, Lili
Zheng, Anqi
Abrégé
The invention relates to an anti-coronavirus polypeptide as well as derivatives and application thereof, provides the anti-coronavirus polypeptide, and provides cholesterol-containing derivatives of the polypeptide on the basis of the anti-coronavirus polypeptide. Particularly, the original strain and the variant strain of the SARS-COV-2 have an unexpected inhibition effect, can be used for preparing medicines or vaccines for preventing or treating the new coronavirus, and have great prevention or treatment potential.
A61K 38/16 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés
A61K 47/54 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique
A61K 47/60 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique macromoléculaire, p. ex. une molécule oligomérique, polymérique ou dendrimérique obtenu par des réactions autres que celles faisant intervenir uniquement des liaisons non saturées carbone-carbone, p. ex. polyurées ou polyuréthanes le composé organique macromoléculaire étant un oligomère, un polymère ou un dendrimère de polyoxyalkylène, p. ex. PEG, PPG, PEO ou polyglycérol
A61P 31/14 - Antiviraux pour le traitement des virus ARN
2.
POLYPEPTIDE DRUG SOLUTION PREPARATION AND METHOD FOR PREPARING SAME
The present application relates to the technical field of pharmaceutical preparations and provides a polypeptide drug liquid preparation and a method for preparing same. The polypeptide drug liquid preparation comprises the following components in percentage by mass: 0.01-5% of HY3000; 0.1-20% of a surfactant and/or a solubility enhancer; 0.5-10% of an osmotic pressure regulator; 0.001-0.2% of a pH regulator; and 64.8-99.4% of a solvent. The provided polypeptide pharmaceutical preparation enhances the stability of HY3000 in a liquid, and use risks borne by a patient are reduced.
A61K 47/12 - Acides carboxyliquesLeurs sels ou anhydrides
A61K 47/18 - AminesAmidesUréesComposés d’ammonium quaternaireAcides aminésOligopeptides ayant jusqu’à cinq acides aminés
A61K 47/26 - Hydrates de carbone, p. ex. polyols ou sucres alcoolisés, sucres aminés, acides nucléiques, mono-, di- ou oligosaccharidesLeurs dérivés, p. ex. polysorbates, esters d’acide gras de sorbitan ou glycyrrhizine
A61P 11/00 - Médicaments pour le traitement des troubles du système respiratoire
A61P 31/14 - Antiviraux pour le traitement des virus ARN
Disclosed are a method for purifying a GLP-1 analog and the use thereof. The purification method comprises: performing reversed-phase purification on a crude peptide solution, performing desalination using a mixed solution of water and an organic solvent as a mobile phase to obtain a refined peptide solution of GLP-1 analog, adjusting the pH to 3.5-5.5, and precipitating at -20°C to 25°C. In the purification method, after reversed-phase purification, desalination and pH adjustment are performed rather than vacuum concentration or membrane concentration, and then precipitation is directly performed without rotary evaporation being required. On one hand, production costs and energy consumption are reduced, thereby improving the efficiency. On the other hand, the obtained purified product is a solid with good stability, can be stored for a long time, is not easily degradable, and is convenient to transfer. In addition, the purification process is simple and efficient, and the precipitation rate is high, which is conducive to large-scale production.
INSTITUTE OF MICROBIOLOGY, CHINESE ACADEMY OF SCIENCES (Chine)
HYBIO PHARMACEUTICAL CO., LTD. (Chine)
Inventeur(s)
Gao, Fu
Zeng, Shaogui
Wang, Qihui
Tang, Yangming
Chen, Jiantao
Wu, Lili
Zheng, Anqi
Abrégé
Provided is an anti-coronavirus polypeptide, and on this basis, cholesterol-containing derivatives of the polypeptide are provided. These polypeptide derivatives yield an unexpected inhibitory effect on coronaviruses, and in particular prototype strains and variant strains of SARS-CoV-2, can be used for preparing a drug or vaccine for preventing or treating novel coronavirus, and has a great prevention or treatment potential.
The present invention relates to the technical field of polypeptide synthesis, in particular to a method for synthesizing a GLP-1 analog. In the present invention, fragment 1 and fragment 2 respectively at positions 1-4 and positions 5-12 of an N terminus of a GLP-1 analog are firstly synthesized, and then the remaining amino acids, fragment 2 and fragment 1 are sequentially coupled on a solid-phase carrier in a sequence from a C terminus to the N terminus to obtain a peptide resin which is cleaved to obtain a crude peptide. The GLP-1 analogs, namely liraglutide and semaglutide, are synthesized using a specific synthesis strategy of the present invention, so that the purity and the total yield of the crude peptide are high, the synthesis process is simple, and the method is suitable for large-scale production.
C07K 1/04 - Procédés généraux de préparation de peptides sur des supports
C07K 1/06 - Procédés généraux de préparation de peptides utilisant des groupes protecteurs ou des agents d'activation
C07K 1/08 - Procédés généraux de préparation de peptides utilisant des groupes protecteurs ou des agents d'activation utilisant des agents d'activation
The present invention relates to the technical field of polypeptide synthesis, in particular to a method for synthesizing a GLP-1 analog. In the present invention, fragment 1 at positions 1-4 of an N terminus of a GLP-1 analog is firstly synthesized, and then amino acids as shown in SEQ ID NO: 2 and fragment 1 are sequentially coupled on a solid-phase carrier in a sequence from a C terminus to the N terminus to obtain a peptide resin which is cleaved to obtain a crude peptide. Liraglutide and semaglutide are synthesized using a specific synthesis strategy of the present invention, so that the purity and the yield are high, and the amount of the impurity Des-Thr5 is small. Moreover, in the present invention, the synthesis process is simple, and the method is suitable for large-scale production.
Disclosed are a liraglutide variant, a preparation method therefor, and an application thereof. The twelfth amino acid Ser of the liraglutide variant is allosterically regulated to a D-type amino acid. The biological activity of the liraglutide variant provided by the present invention is twice that of the liraglutide, and the liraglutide variant can be used for preparing hypoglycemic and weight loss drugs.
A method for purifying a long chain polypeptide includes: 1) purification step: connecting two chromatographic columns in series to separate a crude product, in which the particle size of a packing in an upstream chromatographic column is larger than that in a downstream chromatographic column; optionally, the method further includes step 2): using the upstream chromatographic column in step 1) for a salt conversion, loading the target peak product obtained in step 1) and rinsing with 95-85% of the A2 and 5-15% of the B for 15-30 min for a desalination, wherein A2 phase is an acetic acid aqueous solution with a volume ratio of 0.05%-0.2%; B phase is an organic phase acetonitrile, and the detection wavelength is 230 nm.
C07K 1/20 - Chromatographie de partage, de phase inverse ou d'interaction hydrophobe
C07K 14/435 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains
Provided is a salt conversion method for a GLP-1 analogue, comprising the following steps: 1) sample preparation: preparing a purified fraction of the GLP-1 analogue; 2) sample dilution: diluting the purified fraction by using deionized water; 3) sample concentration: performing concentration by using an ultrafiltration membrane; and 4) sample salt conversion: performing salt conversion by using the ultrafiltration membrane in step 3). By using ultrafiltration technology for salt conversion, the recovery rate is higher than that of reversed-phase salt conversion; by using ultrafiltration technology for salt conversion, an obtained sample solution can be freeze-dried without being concentrated under reduced pressure, the process is simple, and the overall efficiency is high; by using ultrafiltration technology for salt conversion, no organic solvent is used, no organic waste liquid is produced, and costs are reduced, and the method is also more environmentally friendly.
Disclosed is a method for purifying a GLP-1 analog, the method comprising the following steps: 1) purifying a GLP-1 analog by means of anion exchange; 2) purifying the purified substance obtained in 1) by means of reversed-phase chromatography. In the first step of purification, anion exchange purification technology that is more environmentally friendly, has lower solvent cost, and the capacity of which is larger is used, which achieves the enrichment of a target substance, and is complementary to reversed-phase chromatography technology, removing the amino acid deletion impurities that are difficult to remove during reversed-phase purification, and also reducing the cost and environmental protection pressure; in the second step of purification, high-resolution reversed-phase purification technology is used to remove isomer impurities, side reaction impurities, etc. that cannot be removed by means of anion exchange purification, and finally, a GLP-1 analog with a purity of ≥ 99.0% and a single impurity of ≤ 0.15% is obtained.
Disclosed is a method for desalting polypeptides, the method comprising loading a polypeptide sample onto a preparative column, rinsing the column with mobile phases A1 and B, then rinsing the column with mobile phases A2 and B, and finally performing gradient elution with A2 and B; collecting the sample; performing rotary evaporation under reduced pressure; and freeze-drying the product to obtain desalted refined polypeptides. In the present method, salt transfer can be performed on a reversed-phase high-efficiency preparative chromatography system by taking a silica filler with a bonded alkyl group as the stationary phase. The method solves the problem of it being difficult to elute samples during desalting without needing additional equipment and materials, and during salt transfer, can further remove impurities, improve sample purity, reduce sample volume after salt transfer, and increase sample concentration. The whole process is simple to operate and has a short production cycle, which is conducive to large-scale industrial production.
The present invention relates to the technical field of impurity synthesis, and particularly to a teriparatide impurity F. It is discovered that aspartimide impurities will be produced during the production and storage process of teriparatide, named as impurity F, and the discovery and synthesis of the impurity is beneficial to the quality control of teriparatide active pharmaceutical ingredient; by using the synthesis method, the purity of a crude peptide can reach 42%, and the purity of a refined peptide can reach 92% after purification. Compared with the prior art, a product has a high purity, is easy to purify, and has a correspondingly increased yield.
Provided is a desalination method using the lyophilization principle, comprising: eluting volatile salt; and performing vacuum freeze drying to remove related salts, to control acid radical content.
Provided is a solid-phase synthesis method for degarelix. The solid-phase synthesis method comprises: 1) coupling of a peptide resin: according to an Fmoc solid phase synthesis method, coupling amino acids Fmoc-D-Ala-OH, Fmoc-Pro-OH, Fmoc-Lys(Boc,iPr)-OH, Fmoc-Leu-OH, Fmoc-D-4Aph(Cbm)-OH, Fmoc-4Aph(Hmb,Hor)-OH, Fmoc-Ser(tBu)-OH, Fmoc-D-3Pal-OH, Fmoc-D-4Cpa-OH, and Fmoc-D-2Nal-OH one by one to a solid phase carrier; 2) N-terminal acetylation of the peptide resin; and 3) obtaining degarelix crude peptide after pyrolysis of the peptide resin.
Disclosed is a method for preparing Ularitide, comprising: dividing, according to the feature that the peptide sequence of Ularitide contains two Cys, the Ularitide into three parts: fragment A: H-Thr-Ala-Pro-Arg-Ser-Leu-Arg-Arg-Ser-Ser-NHNH2, fragment B: H-Cys-Phe-Gly-Gly-Arg-Met-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-NHNH2, and fragment C: Cys-Asn-Ser-Phe-Arg-Tyr-OH. Hydrazide groups in the fragments respectively react with sodium nitrite and MPAA to generate thioester, and a condensation reaction can selectively occur between the thioester and a polypeptide fragment in which the N-terminal is Cys. Different from a conventional fragment method, the fragment in the present invention does not have a protecting group on the side chain, has good solubility in water, and does not have the problem of difficulty in coupling. The product obtained has high purity, easy purification, simple operation, high production efficiency, high product quality, and low cost, and is suitable for industrial production, etc.
Disclosed is a method for synthesizing octreotide, the method comprising the following steps: 1) selecting a 2-CTC resin as a starting point of synthesis to prepare an Fmoc-Thr(tBu)-OL-2CTC resin; 2) sequentially coupling orthogonally protected cystine, Fmoc-Thr(tBu)-OH, Fmoc-Lys(Boc)-OH, Fmoc-D-Trp(Boc)-OH and Fmoc-Phe -OH according to an Fmoc/tBu strategy, removing an Alloc protecting group for the orthogonal protection of cystine by using pd(pph3)4 and phenylsilane, then coupling Boc-D-Phe-OH, and then carrying out an intramolecular amidation reaction to form a ring; and 3) cleaving a peptide fragment by means of a lysis liquid to obtain a crude octreotide peptide. Provided is a solid-phase synthesis method which avoids an oxidation reaction that forms a ring, thereby avoiding many problems caused by existing methods; in addition, the method of the present invention has many advantages such as simple operation, a simplified process, and being environmentally friendly.
Disclosed is a method for preparing nesiritide, comprising the following steps: 1) synthesizing an intermediate 1 by means of a solid phase synthesis method; 2) synthesizing an intermediate 2 by means of a solid phase synthesis method; activating a C-terminal carboxyl group of the intermediate 2 to obtain an intermediate 3, and removing a side chain protecting group for the intermediate 3 to obtain an intermediate 4; 3) reacting the intermediate 1 and intermediate 4 by means of disulfide bond exchange to form an intermediate 5 with an intermolecular disulfide bond; 4) allowing the intermediate 5 to form an amide bond under the action of a cyclization-promoting agent, so as to obtain an intermediate 6, and then removing an Fmoc protecting group therefrom to obtain a nesiritide crude product; and 5) purifying the nesiritide crude product to obtain the nesiritide. In the present invention, the used method of combining a liquid phase and a solid phase has a high preparation efficiency and achieves a high purity.
A teriparatide sustained release gel injection solution, made of the following ingredients: teriparatide, a pH buffer component, bioadhesive material, temperature-sensitive gel material, a pH regulator, and a solvent; the temperature-sensitive gel material is selected from a combination of temperature-sensitive poloxamer and glycerin, the bioadhesive material is selected from chitosan, hyaluronic acid, cellulose derivatives, polyacrylic acid or a combination thereof, and the solvent is water. The present teriparatide sustained release gel injection solution has a sustained release lasting several days, significantly reducing the number of medicine administrations, increasing patient compliance and improving the therapeutic effect, and also avoiding the use of bacteriostatic agents whilst achieving the same effect.
A ranolazine skeleton sustained-release tablet and a preparation method therefor. A regulatory layer is provided outside a drug layer in the tablet core of the ranolazine skeleton sustained-release tablet, so as to form a double-layer sustained-release tablet. The weight percentage of the drug layer in the whole tablet core is 60% to 95%, and the weight percentage of the regulatory layer in the whole tablet core is 5% to 40%. The drug layer is made of the following raw material components: ranolazine, a skeleton sustained-release material and other auxiliary materials. The weight percentage of each component accounting for the tablet weight is as follows: 35% to 90% of ranolazine, 3% to 40% of the skeleton sustained-release material, and 1% to 15% of the other auxiliary materials. The regulatory layer is made of the following raw material components: a skeleton sustained-release material and other auxiliary materials. The weight percentage of each component accounting for the tablet weight is as follows: 2% to 35% of the skeleton sustained-release material, and 1% to 15% of the other auxiliary materials. The preparation method comprises the following steps: 1) preparing drug layer particles; 2) preparing regulatory layer particles; and 3) pressing the prepared drug layer particles and the regulatory layer particles together into a double-layer tablet.
A61K 31/495 - Composés hétérocycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. guanéthidine ou rifamycines ayant des cycles à six chaînons avec deux azote comme seuls hétéro-atomes d'un cycle, p. ex. pipérazine
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
222212311, and condensing a polypeptide resin to obtain a cyclized carbetocin peptide resin; lysing and precipitating same to obtain a crude peptide; and separating, purifying, and freeze-drying the crude peptide.
An adrenaline injection and a preparation method therefor. The adrenaline injection is composed of the following components in percentage by weight: adrenaline or a salt thereof 0.03-0.15%, an osmotic pressure regulator 0.03-0.08%, an antioxidant 0.08-0.25%, a buffering agent 0.05-0.2%, a pH regulator 8-15%, and the remaining amount of water for injection; the buffering agent is selected from one or two among sodium dihydrogen phosphate and disodium hydrogen phosphate; and the pH regulator comprises an acidic pH regulator and an alkaline pH regulator.
The present invention relates to the field of polypeptide synthesis, and provides a method for synthesizing Etelcalcetide. The method uses β-S(Trt)-D-Arg(Boc)3-OH as a raw material, replaces alanine in a peptide sequence with cysteine, and uses a native chemical ligation (NCL) method for coupling reaction. The method uses intramolecular migration reaction of S to N to complete coupling, overcomes the problem of difficulty in coupling between fragments under the action of a conventional coupling reagent, improves the coupling efficiency between peptide fragments, and has a total yield of 71.3%. The present invention reduces production costs and is suitable for large-scale production.
Disclosed is a pharmaceutical composition comprising linaclotide, comprising linaclotide, a filler, a disintegrant and a lubricant, wherein the mass ratio of linaclotide is 0.02-0.2%, the mass ratio of the filler is 88.8-95%., the mass ratio of the disintegrant is 4-10%, and the mass ratio of the lubricant is 0.5-1.5%. The direct compression tablet of linaclotide is prepared from the above-mentioned pharmaceutical composition by means of the following method, which comprises the following steps: 1) uniformly mixing linaclotide with a filler, disintegrant and lubricant; and 2) compressing the mixed powder obtained in 1) to obtain plain tablets, wherein the hardness of the compressed tablets is controlled at 6-10 kgf.
An isosorbide mononitrate sustained release tablet and a preparation method therefor. The tablet is prepared from isosorbide mononitrate, a corrosive matrix material, a binder, a lubricant, and talc powder. The parts by mass of the components are: 15-20 parts of isosorbide mononitrate, 60-65 parts of a corrosive matrix material, 8-11 parts of a binder, 0.5-1.5 parts of a lubricant, and 5-20 parts of talc powder. By adding the talc powder, the softening problem of a wax matrix tablet is alleviated, the prepared tablet has high hardness and good appearance, and the release effect of the tablet is the same as that of a RLD.
A61K 9/22 - Pilules, pastilles ou comprimés du type à libération prolongée ou discontinue
A61K 31/34 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à cinq chaînons avec un oxygène comme seul hétéro-atome d'un cycle, p. ex. isosorbide
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
The present invention relates to a synthesis method for ZP-1609, comprising the steps of: 1) selectively reacting to completion, 4-amino-L-proline tert-butyl ester with N-hydroxysuccinimide benzoate to obtain an intermediate product; 2) linking the intermediate product obtained in step 1) with Boc-Gly-OH by means of a DCC/HOBT liquid amide condensation method to obtain an intermediate product; and 3) hydrolyzing the intermediate product obtained in step 2) with hydrochloric acid to remove the protecting group -Boc of glycine and the protecting group -tBu of the carboxyl of proline, and further acidifying the product with hydrochloric acid to give ZP-1609. The process is simple in operation and post-treatment is convenient, and does not need additional N-terminal protection. The protecting groups -Boc and -tBu are both unstable under acidic conditions, and removal of the protecting groups and acidification can be performed with hydrochloric acid in one step, reducing the steps required for the repeated removal of the protecting groups, and reducing the steps of removing protecting groups with an alkali and then performing acidification with hydrochloric acid in existing processes, simplifying operations and increasing yield.
C07D 207/16 - Atomes de carbone comportant trois liaisons à des hétéro-atomes, avec au plus une liaison à un halogène, p. ex. radicaux ester ou nitrile
C07D 233/02 - Composés hétérocycliques contenant des cycles diazole-1, 3 ou diazole-1, 3 hydrogéné, non condensés avec d'autres cycles ne comportant pas de liaisons doubles entre chaînons cycliques ou entre chaînons cycliques et chaînons non cycliques
C07C 233/81 - Amides d'acides carboxyliques ayant des atomes de carbone de groupes carboxamide liés à des atomes de carbone de cycles aromatiques à six chaînons ayant l'atome d'azote d'au moins un des groupes carboxamide lié à un atome de carbone d'un radical hydrocarboné substitué par des groupes carboxyle
A synthesis method for thymosin Tα-1, comprising the following steps: 1) according to an Fmoc solid-phase synthesis method, coupling amino acids one by one to a solid-phase carrier, and synthesizing the 5-peptide resin of a side-chain protecting group; 2) preparing a 7-peptide resin having an Hmb protecting group; 3) according to the Fmoc solid-phase synthesis method, continuing to couple residues at positions 1-21 to obtain a 28-peptide resin; and 4) cleaving and removing the C-terminal resin and all the protecting groups of the 28-peptide resin so as to obtain Tα-l crude peptide. By introducing the Hmb protecting group to Val at position 23, a β-sheet is reduced in the process of peptide chain coupling, thereby improving reaction efficiency.
C07K 17/02 - Peptides immobilisés sur, ou dans, un support organique
C07K 14/47 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés provenant de mammifères
Provided is a preparation method of verakatide, comprising the following steps: 1) preparing the fully protected verakatide main chain-solid phase synthetic resin by solid-phase synthesis; 2) cracking to remove the side chain protecting group P of Cys; 3) performing solid-phase electrochemical oxidation, coupling cysteine through disulfide bonds; 4) cracking all protecting groups and solid-phase synthetic resin to obtain the verakatide crude peptide; optionally, 5) performing chromatographic purification to obtain verakatide fine peptide; wherein, the solid-phase electrochemical oxidation is to electrolyze the polypeptide-solid-phase synthetic resin obtained in step 2) with the side chain protecting group of Cys removed in the electrolyte and the solution until the disulfide bond reaction is complete; P is the side chain protecting group of Cys. This method can increase the utilization rate of fragment peptide resin, increase the utilization rate of main chain fragments and atom utilization rate, thereby reducing production costs, avoiding the use of 2,2-dithiodipyridine compounds in the original research patent, which is more environmentally friendly and advocates the concept of green chemistry.
Provided is a pramipexole sustained release tablet, wherein same is prepared from the following components, with the sum of the components being 100%: 0.12-0.45％ of pramipexole dihydrochloride, 50-60％ of a filler, 25-35％ of a sustained release matrix, 8-12％ of an adhesive, 0.3-3％ of a glidant, and 0.1-1.0％ of a lubricant. The sustained release matrix is Eudragit RD, hydroxypropyl methylcellulose K100M or a combination thereof, preferably the combination of Eudragit RD and hydroxypropyl methylcellulose K100M. The ratio of the glidant to the lubricant is glidant : lubricant = 0.5 to 10, preferably 0.6 to 8.
A61K 47/32 - Composés macromoléculaires obtenus par des réactions faisant intervenir uniquement des liaisons non saturées carbone-carbone, p. ex. carbomères
Disclosed is a method for synthesizing a polypeptide-derived compound, comprising the following steps: step 1: attaching Fmoc-Gly-OH to a resin to obtain a Fmoc-Gly resin; step 2: in accordance with a sequence of a peptide-derived compound, sequentially coupling amino acids by a Fmoc/tBu scheme to obtain a peptide resin with a main chain of the polypeptide-derived compound; step 3: removing a protecting group on Lys 26 and sequentially coupling Fmoc-AEEA-AEEA-OH and Octadecanoicacid(OtBu)-Glu-OtBu to obtain a peptide resin with the polypeptide-derived compound; step 4: cleaving the peptide resin with the polypeptide-derived compound and simultaneously removing a side chain protecting group to obtain a crude peptide-derived compound; and selectively, step 5: purifying by RP-HPLC to obtain a pure peptide-derived compound. The method is simple and has high synthesis yield as well as high purity.
C07K 1/20 - Chromatographie de partage, de phase inverse ou d'interaction hydrophobe
C07K 1/04 - Procédés généraux de préparation de peptides sur des supports
C07K 1/06 - Procédés généraux de préparation de peptides utilisant des groupes protecteurs ou des agents d'activation
C07K 1/08 - Procédés généraux de préparation de peptides utilisant des groupes protecteurs ou des agents d'activation utilisant des agents d'activation
Provided is a method for polypeptide purification, comprising the following steps: crude purification of a first aqueous two-phase system, refined purification of a second aqueous two-phase system, and reverse phase, gel or ion desalination. The first aqueous two-phase system comprises a first polymer and a first preparation; the second aqueous two-phase system comprises a second polymer and a second preparation; the first polymer or the second polymer is independently selected from polyethylene glycol, polypropylene glycol or glucan; the first polymer or the second polymer may be the same or different; the first preparation is ammonium sulfate, ammonium bicarbonate, ammonium acetate, potassium dihydrogen phosphate, phosphoric acid or sodium chloride; and the second preparation is phosphate, glacial acetic acid, potassium chloride or ammonium acetate. The polypeptide is particularly liraglutide.
Disclosed is a method for preparing thymalfasin, wherein acetyl-salicylaldehyde and acetyl-salicylaldehyde analogs are used for preparing thymalfasin by performing selective N-terminal acetylation of the thymalfasin 28 peptide. The method does not require the other aminos of the thymalfasin 28 peptide to be protected, thereby avoiding expensive raw materials and tedious removal operations for the special protection of lysine side chain aminos required by other acetylation methods.
Provided is a method for synthesizing romidepsin, comprising the following steps: 1) coupling a solid phase synthetic resin with Fmoc-L-Val-OH under the action of an activator to obtain an intermediate I; 2) according to an Fmoc solid phase synthesis strategy, sequentially using Fmoc-L-Thr-OH, Fmoc-D-Cys(R)-OH, Fmoc-D-Val-OH and (R)-3-tert-butoxy-7-mercapto-4-heptenoic acid in a one-by-one manner to perform polypeptide chain extension coupling to obtain an intermediate V; 3) removing the hydroxyl group on the L-Thr residue side chain of the intermediate V to form a double bond, so as to obtain an intermediate VI; 4) cracking the intermediate VI and removing the resin and side chain protecting groups, so as to obtain an intermediate VII; 5) oxidizing the intermediate VII to form an intramolecular disulfide bond, so as to obtain an intermediate VIII; and 6) subjecting the intermediate VIII to an intramolecular esterification reaction to obtain romidepsin.
A method for purifying a polypeptide similar to GLP-1, the purification method uses supercritical chromatography and is characterized in that butyl-bonded silica gel is used as a chromatographic column of a stationary phase, an Al phase in a mobile phase is carbon dioxide, and a B phase is an organic solvent; the organic solvent is selected from among methanol, acetonitrile, or a mixture thereof; the temperature of a column is 30-40°C, and linear elution is performed under a certain elution pressure, the elution pressure being linear elution from a column pressure at a column temperature X0.25 to a column pressure at a column temperature X0.3, and the unit of column pressure being MPa. The preparation method is environmentally friendly, and is highly efficient, has high purity and has high yield.
22 (8) and a compound Boc-Tyr-Phe-Gln-Asn-active ester (13) are synthesized in segments using the liquid phase method, a compound (14) is obtained by connecting the compound (13) with the compound (8), a compound (15) is obtained after coupling the compound (14) with Boc-Cys(trt)-OH and deprotecting same, a compound (16) is obtained by connecting the compound (15) with the compound (3), and terlipressin is obtained by means of the oxidation of the compound (16).
C07K 1/06 - Procédés généraux de préparation de peptides utilisant des groupes protecteurs ou des agents d'activation
C07K 1/08 - Procédés généraux de préparation de peptides utilisant des groupes protecteurs ou des agents d'activation utilisant des agents d'activation
36.
PREPARATION METHOD FOR SYNTHESIS OF POLYPEPTIDE CONTAINING TWO PAIRS OF DISULFIDE BONDS AND KIT THEREOF, AND METHOD FOR PREPARING PLECANATIDE
Disclosed is a preparation method for the synthesis of a polypeptide containing two pairs of disulfide bonds, wherein the method uses oxidation reaction to synthesize a linear peptide into a polypeptide having two pairs of disulfide bonds in liquid phase. In the prior art, solid-phase synthesis is mainly used to synthesize a linear peptide into a polypeptide having two pairs of disulfide bonds, which is poor in effect and low in yield. Therefore, through a large number of experiments, the applicant has undertaken a targeted study into how to synthesize the linear peptide into the polypeptide having two pairs of disulfide bonds, and has found that the linear peptide can be synthesized into the polypeptide having two pairs of disulfide bonds in one step by means of oxidation reaction and liquid-phase synthesis, thereby avoiding difficult separation and purification and low yield caused by complex components in a solution which is due to a cyclization step for the linear peptide being performed twice in the solution. This technical solution is highly inventive in synthesizing a polypeptide having two pairs of disulfide bonds by means of oxidation reaction and liquid-phase synthesis.
A Rivaroxaban pharmaceutical composition and a preparation method therefor. The Rivaroxaban pharmaceutical composition consists of Rivaroxaban, polyethylene glycol, a binder, a filler, a disintegrant, a surfactant and a lubricant in a certain ratio. The preparation method comprises: crushing Rivaroxaban and dispersing the resultant in an aqueous solution of polyethylene glycol to prepare a Rivaroxaban suspension, spraying the suspension into a mixture of components other than the lubricant and performing granulation, performing drying, mixing the granule with the lubricant, and performing tabletting so as to obtain the Rivaroxaban pharmaceutical composition.
A61K 31/5377 - 1,4-Oxazines, p. ex. morpholine non condensées et contenant d'autres hétérocycles, p. ex. timolol
A61K 47/10 - AlcoolsPhénolsLeurs sels, p. ex. glycérolPolyéthylène glycols [PEG]PoloxamèresAlkyléthers de PEG/POE
A61K 47/20 - Composés organiques, p. ex. hydrocarbures naturels ou synthétiques, polyoléfines, huile minérale, gelée de pétrole ou ozocérite contenant du soufre, p. ex. sulfoxyde de diméthyle [DMSO], docusate, laurylsulfate de sodium ou acides aminosulfoniques
The present invention relates to a complete liquid-phase synthesis method of sinapultide. The complete liquid-phase synthesis method comprises: firstly, synthesising of Fmoc-Leu-Leu-Leu-Leu-Lys(Boc)-OH, and synthesising of complete protected peptide fragment of Fmoc-Leu-Leu-Leu-Leu-Lys(Boc)-Leu-Leu-Leu-Leu-Lys(Boc)-Leu-Leu-Leu-Leu-Lys(Boc)-Leu-Leu-Leu-Leu-Lys(Boc)-OH in two steps based on Fmoc-Leu-Leu-Leu-Leu-Lys(Boc)-OH, and then coupling to Boc-Lys(Boc)-OH complete protected sinapultide by liquid-phase; and cracking same in the condition of a liquid phase to remove protective group Boc. The preparation method is simple, and the yield and purity are relatively high, which save on solvent thereby achieving the aim of environmental protection, and is suitable for mass production.
C07K 1/02 - Procédés généraux de préparation de peptides en solution
C07K 1/04 - Procédés généraux de préparation de peptides sur des supports
C07K 1/06 - Procédés généraux de préparation de peptides utilisant des groupes protecteurs ou des agents d'activation
C07K 1/08 - Procédés généraux de préparation de peptides utilisant des groupes protecteurs ou des agents d'activation utilisant des agents d'activation
C07K 7/08 - Peptides linéaires ne contenant que des liaisons peptidiques normales ayant de 12 à 20 amino-acides
C07K 14/00 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés
The present invention relates to the technical field of polypeptide synthesis. Disclosed is a method for synthesizing goserelin. The synthesis method comprises: coupling Azagly and resin; sequentially coupling amino acids at an Azagly-resin amino terminus; using a removal agent containing tetrakistriphenylphosphine palladium and morpholine to remove an Arg guanidino protecting group in the peptide resin obtained in step B; and using a lysis solution to lyse the peptide resin obtained in step C, so as to obtain goserelin.
The present invention provides a purification method for dulaglutide. The method comprises: crushing bacteria expressing dulaglutide, and obtaining filtrate after filtering; extracting the filtrate by using an extractant to collect an organic layer; after the organic layer is mixed with water, extracting by using a back-extractant to collect a water layer; obtaining dulaglutide by lyophilizing the water layer. The extractant is at least one of methyl alcohol, ethyl alcohol, isopropanol, acetone, tetrahydrofuran, acetonitrile, normal butanol, isobutanol, and tertiary butanol; the back-extractant is at least one of ethyl acetate, isopropyl acetate, diethyl ether, isobutyl ether, and methyl tert-butyl ether.
Disclosed are a slow release pasireotide microsphere and a preparation method thereof. The microsphere is prepared using pasireotide as an active ingredient, and a microsphere support polymer, a protecting agent, a surfactant and a suspending agent. The microsphere support polymer is selected from polylactic-co-glycolic acids (PLGA). The suspending agent is selected from one or a combination of any two or more of tragacanth, gum arabic, carbomer and sodium alginate. The preparation method of the microsphere is a multiple emulsion method. Addition of the suspending agent allows for a release time of the pasireotide microsphere of up to 28 days.
An integrilin thioether compound, having a structure as represented by formula I. Also disclosed is a method for preparing integrilin thioether, which is prepared by using a solid phase synthesis method. A terminal is synthesized by using 3-chloropropionic acid; by using 1,4-dimethylpiperazine as an alkali, cyclization is implemented in a solvent, and a thioether bond is formed. The integrilin thioether compound has high stability, the preparation method is simple, a better anti-platelet coagulation function is achieved.
C07K 7/06 - Peptides linéaires ne contenant que des liaisons peptidiques normales ayant de 5 à 11 amino-acides
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
A61K 38/08 - Peptides ayant de 5 à 11 amino-acides
A preparation method of Plecanatide comprises the following steps: 1) sequentially coupling an amino acid at position 16-7 on a solid-phase synthetic resin according to a Fmoc solid-phase synthesis strategy; 2) after removal of the Fmoc protecting group, processing a reagent for removing a Mmt protecting group and removing the side-chain Mmt protecting group of Cys at positions 7 and 15; 3) forming through bonding reaction a disulfide bond between Cys at position 7 and Cys at position 15; 4) according to the Fmoc solid-phase synthesis strategy, sequentially coupling an amino acid at position 6-1; 5) removing the Fmoc protecting group, and completing a disulfide bond between Cys at position 4 and Cys at position 12 through oxidation reaction; and 6) removing all the side-chain protecting groups, pyrolyzing the resin by using a cracking reagent, and precipitating by adding diethyl ether to obtain Plecanatide. The method is simple and efficient.
A detection method for a vildagliptin enantiomer, separating the vildagliptin enantiomer, and vildagliptin and impurities thereof by using a polysaccharide derivative positive-phase coating type chiral chromatographic column by means of isocratic elution, the separation degree being greater than 1.5. Experiments show that the detection limit of the vildagliptin and an isomer thereof is 1.0 μg/ml and the quantitative limit is 2.1 μg/ml, and the method is high in sensitivity. The vildagliptin enantiomer has a concentration range of 2.0-12.5 μg/ml and has a linear correlation coefficient R of 0.9997, and is good in linearity. The method is good in accuracy and repeatability; detection is carried out under the condition of the presence of auxiliary materials, and no interference is seen.
The invention belongs to the technical field of pharmaceutical chemistry, in which a method for preparing teriparatide is disclosed. First, peptide sequences 1-16 (fragment A) and peptide sequences 17-34 (fragment B) of teriparatide are separately synthesized, and then the two fragments are coupled to obtain a teriparatide crude peptide, which is then purified to obtain teriparatide. The teriparatide product obtained by the present invention has high purity and is easily purified.
Disclosed is a glatiramer acetate multivesicular liposome, wherein a liposome membrane is formed by a normal phospholipid, triglyceride and a charged phospholipid, and the glatiramer acetate as an active ingredient is also encapsulated in the multivesicular liposome. The liposome membrane also comprises cholesterol. The mass ratio of the normal phospholipid to charged phospholipid to triglyceride is 3-10 : 1 : 0.8-1.2.
A61K 9/127 - Vecteurs à bicouches synthétiques, p. ex. liposomes ou liposomes comportant du cholestérol en tant qu’unique agent tensioactif non phosphatidylique
A61K 38/16 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés
A61K 47/14 - Esters d’acides carboxyliques, p. ex. acides gras monoglycérides, triglycérides à chaine moyenne, parabènes ou esters d’acide gras de PEG
A61K 47/16 - Composés organiques, p. ex. hydrocarbures naturels ou synthétiques, polyoléfines, huile minérale, gelée de pétrole ou ozocérite contenant de l'azote
A61K 47/24 - Composés organiques, p. ex. hydrocarbures naturels ou synthétiques, polyoléfines, huile minérale, gelée de pétrole ou ozocérite contenant des atomes autres que des atomes de carbone, d'hydrogène, d'oxygène, d'halogènes, d'azote ou de soufre, p. ex. cyclométhicone ou phospholipides
49.
TRIMETAZIDINE SUSTAINED-RELEASE TABLET AND PREPARATION METHOD THEREFOR
Disclosed are a trimetazidine sustained-release tablet and a preparation method therefor. The sustained-release tablet comprises a coating material for tablet film coatings and a tablet core coated by the coating material. The tablet core comprises pellets and excipients. The pellets successively comprise, from inside to outside, a drug-loading coating layer, a sustained-release coating layer and a protective coating layer. The drug-loading coating layer comprises trimetazidine and an adhesive for drug-loading pellet coatings. The sustained-release coating layer comprises a coating material for sustained-release pellet coatings, a pore-forming agent, a plasticizer and an anti-adhesion agent. The protective coating layer comprises a coating material for protective pellet coatings and a plasticizer for protective pellet coatings. The excipients comprise a filler, a disintegrating agent and a lubricant. The sustained-release tablet is coated with a protective layer outside of the sustained-release layer, thereby solving the problems, which easily occur during the process of tableting the pellets, such as decreased sustained release ability caused by the destruction of the sustained-release layer, and content uniformity not qualifying as a result of excessive fluidity, and also solving the problem of the burst release of the readily-soluble drug, trimethazine, in water.
A61K 31/495 - Composés hétérocycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. guanéthidine ou rifamycines ayant des cycles à six chaînons avec deux azote comme seuls hétéro-atomes d'un cycle, p. ex. pipérazine
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
The present invention provides a method for purifying a long chain polypeptide. The method comprises step 1), i.e., a purification step: using two chromatography columns to be connected in series for crude product separation, wherein the particle size of the packing in the upstream chromatography column is greater than the particle size of the packing in the downstream chromatography column; optionally, the method further comprises step 2) of transforming salt: using the upstream chromatography column in step 1) to transform salt, and performing sample loading on a target peak product obtained in step 1); washing for 15-30 min with 95%-85% of A2 and 5%-15% of B for desalination, wherein the A2 phase is aqueous acetic acid having a volume ratio of 0.05%-0.2%, and the B phase is organic phase acetonitrile of which the detection wavelength is 230 nm.
22-AAn-(3-carboxyl-solid-phase synthetic resin)-Pro-OH; 4) performing solid-phase head-to-tail cyclization: coupling the amino at AAn to the carboxyl at Pro; 5) cracking the solid-phase synthetic resin to prepare an intermediate crude cyclic peptide; and 6) removing the carboxyl at 3- position of the tail Pro from the intermediate crude cyclic peptide under the effect of a decarboxylation agent, so as to prepare the cyclic peptide containing proline. The method is novel, the synthesis conditions are mild, and the process is simple and stable.
2222-AAn-Asp-(solid-phase synthetic resin)-OH; 4) performing end-to-end condensation and cyclization on the amino acids at the ends of a long chain of the polypeptide obtained in step 3); 5) performing pyrolysis to remove the product obtained in step 4) from the resin to obtain an intermediate crude cyclic peptide; and 6) removing a side-chain carboxyl of the aspartic acid from the intermediate crude cyclic peptide under the effect of L-aspartic acid-β-decarboxylase to obtain a finished product.
Provided is a method for preparing eptifibatide by synthesis, comprising the steps of: (1) using a solid-phase synthetic resin, and successively coupling and synthesizing an eptifibatide-linear peptide resin by Fmoc solid-phase synthesis; (2) cleaving the eptifibatide-linear peptide resin to obtain an eptifibatide-linear crude peptide; (3) dissolving the eptifibatide-linear crude peptide in water and adjusting the pH to 6.9 or less, and adding an oxidant to cause an oxidation reaction or allowing natural oxidation in the air to obtain an eptifibatide crude peptide; (4) purifying a solution of the eptifibatide crude peptide by column chromatography to obtain an eptifibatide refined peptide.
C07K 7/06 - Peptides linéaires ne contenant que des liaisons peptidiques normales ayant de 5 à 11 amino-acides
C07K 1/04 - Procédés généraux de préparation de peptides sur des supports
C07K 1/08 - Procédés généraux de préparation de peptides utilisant des groupes protecteurs ou des agents d'activation utilisant des agents d'activation
C07K 1/10 - Procédés généraux de préparation de peptides utilisant des agents de couplage
C07K 1/20 - Chromatographie de partage, de phase inverse ou d'interaction hydrophobe
Provided is a method for synthesizing Etelcalcetide, comprising the following steps: 1) synthesizing compound 3; 2) synthesizing a polypeptide resin by a solid phase synthetic method: H-D-Ala-D-Arg(Pbf)-D-Arg(Pbf)-D-Ala-D-Arg(Pbf)-solid phase synthetic resin; 3) coupling compound 3 with the polypeptide resin obtained in step 2); and 4) lysing the peptide resin and simultaneously removing a protective group, so as to obtain the Etelcalcetide.
C07K 7/06 - Peptides linéaires ne contenant que des liaisons peptidiques normales ayant de 5 à 11 amino-acides
C07K 1/06 - Procédés généraux de préparation de peptides utilisant des groupes protecteurs ou des agents d'activation
C07K 1/04 - Procédés généraux de préparation de peptides sur des supports
C07K 1/08 - Procédés généraux de préparation de peptides utilisant des groupes protecteurs ou des agents d'activation utilisant des agents d'activation
55.
COMPOUND AND PREPARATION METHOD THEREFOR AND APPLICATION THEREOF
33, and reduce the solubility of a full protective peptide in an aqueous solution; by using the reaction carrier 1/2/3 as a raw material, a liquid-phase synthesis method can reduce the purification steps in each step of the conventional liquid-phase synthesis method and thus improve the production efficiency; the liquid-phase synthesis method using the reaction carrier 1/2/3 as a raw material can effectively reduce the dosage of organic solvent (DMF, DCM) in solid-phase synthesis method, and achieve the effect of reducing waste.
C07C 43/23 - Éthers une liaison sur l'oxygène de la fonction éther étant sur un atome de carbone d'un cycle aromatique à six chaînons contenant des groupes hydroxyle ou O-métal
C07K 1/06 - Procédés généraux de préparation de peptides utilisant des groupes protecteurs ou des agents d'activation
56.
COMPOUND, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF
Disclosed are a compound represented by formula II, a preparation method therefor and an application thereof. Using the compound represented by formula II to synthesize lanreotide has the following advantages: 1. during a reaction, a carrier and a peptide are dissolved and clarified, relating to a homogeneous reaction, which is advantageous for the coupling and ring formation of difficult amino acids, meanwhile a product is precipitated in methanol after the reaction, while an amino acid raw material and a coupling reagent are dissolved in methanol; 2. the raw material and product are separated by means of filtration and washing; 3. the feeding ratio of the amino acid raw material is reduced from 5 times to 1.2-1.3 times, thus a large amount of DMF need not be used, only a small amount of methanol, chloroform, and so on being used, wherein chloroform and the like may be recovered; 4. the yield of one batch production is increased; 5. a Cys(Mmt) protecting group is used to achieve positioned removal, a ring is formed in the environment of the carrier and the protecting group, and then cracking is carried out, thus compared with crude peptide liquid phase ring formation, the operation is simple and the yield is significantly increased.
The present invention relates to a carrier compound for liquid phase synthesis of a polypeptide, a preparation method therefor and use thereof, and specifically discloses a fused ring compound which can be used as a liquid phase carrier of the polypeptide. The fused ring compound is represented by formula (A) or (B), wherein X is selected from H, F, Cl, Br, I or a group bearing hydroxy, amino, carboxy, or halogen, and Y is selected from H, F, Cl, Br or I. The liquid phase synthesis carrier compound of the present invention is simple to prepare and has high reaction efficiency.
A liquid phase spherical carrier as represented by formula I, a preparation method therefor and use thereof. R is a functional group, preferably a group having hydroxyl, amino, carboxyl or halogen. The liquid phase synthesis carrier can be used for liquid phase synthesis of polypeptides, the preparation method therefor is simple, and the synthesis efficiency is high.
C07C 43/253 - Éthers l'atome d'oxygène de la fonction éther étant lié à un atome de carbone d'un cycle aromatique à six chaînons et à un atome de carbone d'un cycle autre qu'un cycle aromatique à six chaînons contenant des groupes hydroxyle ou O-métal
C07C 41/16 - Préparation d'éthers par réactions d'esters d'acides minéraux ou organiques avec des groupes hydroxyle ou O-métal
C07C 217/58 - Composés contenant des groupes amino et hydroxy éthérifiés liés au même squelette carboné ayant des groupes hydroxy éthérifiés liés à des atomes de carbone d'au moins un cycle aromatique à six chaînons et des groupes amino liés à des atomes de carbone acycliques ou à des atomes de carbone de cycles autres que des cycles aromatiques à six chaînons du même squelette carboné avec des groupes amino reliés au cycle aromatique à six chaînons, ou au système cyclique condensé contenant ce cycle, par l'intermédiaire de chaînes carbonées qui ne sont pas substituées de plus par des atomes d'oxygène liés par des liaisons simples avec des groupes amino et le cycle aromatique à six chaînons, ou le système cyclique condensé contenant ce cycle, liés au même atome de carbone de la chaîne carbonée
C07C 213/08 - Préparation de composés contenant des groupes amino et hydroxy, amino et hydroxy éthérifiés ou amino et hydroxy estérifiés liés au même squelette carboné par des réactions n'impliquant pas la formation de groupes amino, de groupes hydroxy ou de groupes hydroxy éthérifiés ou estérifiés
C07K 1/04 - Procédés généraux de préparation de peptides sur des supports
C07K 1/02 - Procédés généraux de préparation de peptides en solution
C07K 1/06 - Procédés généraux de préparation de peptides utilisant des groupes protecteurs ou des agents d'activation
C07K 14/815 - Inhibiteurs de protéase provenant de sangsues, p. ex. hirudine, égline
59.
COMPOUND FOR POLYPEPTIDE LIQUID-PHASE SYNTHESIS CARRIER, PREPARATION METHOD THEREFOR AND USE THEREOF
The present invention relates to a compound for a polypeptide liquid-phase synthesis carrier, a preparation method therefor and use thereof. Specifically, disclosed is a cyclic ketone compound as a polypeptide liquid-phase carrier, having a structure as represented by formula I or II, wherein X is selected from H, F, Cl, Br, I, or a group having a hydroxyl group, an amino group, a carboxyl group, and halogen.
C07C 211/27 - Composés contenant des groupes amino liés à un squelette carboné ayant des groupes amino liés à des atomes de carbone acycliques d'un squelette carboné non saturé contenant au moins un cycle aromatique à six chaînons ayant des groupes amino reliés au cycle aromatique à six chaînons par l'intermédiaire de chaînes carbonées saturées
C07C 43/21 - Éthers une liaison sur l'oxygène de la fonction éther étant sur un atome de carbone d'un cycle aromatique à six chaînons contenant des cycles autres que des cycles aromatiques à six chaînons
C07C 23/36 - Naphtalènes halogénés complètement ou partiellement hydrogénés
C07C 13/62 - Hydrocarbures polycycliques ou leurs dérivés hydrocarbonés acycliques à cycles condensés à plus de trois cycles condensés
C07K 1/02 - Procédés généraux de préparation de peptides en solution
C07K 1/08 - Procédés généraux de préparation de peptides utilisant des groupes protecteurs ou des agents d'activation utilisant des agents d'activation
C07K 1/16 - ExtractionSéparationPurification par chromatographie
C07K 7/06 - Peptides linéaires ne contenant que des liaisons peptidiques normales ayant de 5 à 11 amino-acides
61.
METHOD FOR SOLID PHASE SYNTHESIS OF VASOPRESSIN RECEPTOR PEPTIDE AGONIST SELEPRESSIN
Provided is a method for solid phase synthesis of a vasopressin receptor peptide agonist selepressin. The method comprises the following steps: 1) sequentially coupling a solid-phase resin with amino acids protected by amino groups to synthesize a polypeptide resin H-Cys(allocam)-Phe-Ile-Hgn(Trt)-Asn(Trt)-Cys(allocam)-Pro-Org(i-Pr)-Gly-resin; 2) under solid phase conditions, removing the protective group allocam of cysteine with a ternary catalytic oxidation system and oxidizing the mercapto group into a disulfide bond; and 3) removing the resin and the protecting groups of side chains of Hgn and Asn from the cleavage broth, and purifying same. The method of the present invention does not use an iodine catalyst, greatly reduces post-processing issues, and has the advantages of simple operation, a simplified process, environmental friendliness, high economic efficiency and being suitable for large-scale production, etc.
C07K 1/08 - Procédés généraux de préparation de peptides utilisant des groupes protecteurs ou des agents d'activation utilisant des agents d'activation
C07K 1/04 - Procédés généraux de préparation de peptides sur des supports
C07K 7/06 - Peptides linéaires ne contenant que des liaisons peptidiques normales ayant de 5 à 11 amino-acides
62.
PRAMIPEXOLE HYDROCHLORIDE SUSTAINED RELEASE PREPARATION AND PREPARATION METHOD THEREFOR.
A pramipexole hydrochloride sustained release preparation and a preparation method therefor. The sustained release preparation comprises first sustained-release pellets and third sustained-release pellets. The first sustained-release pellets comprise pramipexole hydrochloride first medicated pellets, a first coating, and a second coating. The third sustained-release pellets comprise pramipexole hydrochloride third medicated pellets and a third coating. The content ratio of pramipexole hydrochloride in the first sustained-release pellets to pramipexole hydrochloride in the third sustained-release pellets is 4:1. The burst effect of pramipexole hydrochloride under acidic conditions can be avoided.
A61K 47/32 - Composés macromoléculaires obtenus par des réactions faisant intervenir uniquement des liaisons non saturées carbone-carbone, p. ex. carbomères
A61K 31/428 - Thiazoles condensés avec des carbocycles
The present invention provides a method of synthesizing PT141. The method of the present invention comprises synthesizing PT141 linear peptide in a solid phase; and adding the linear peptide into a buffer solution and performing cyclization by using one or more of thermolysin, papain, A2 chymotrypsin, trypsin, subtilisin, and butelase 1 to obtain the PT141.
C12P 21/04 - Peptides ou polypeptides cycliques ou pontés, p. ex. bacitracine
C07K 7/56 - Peptides cycliques contenant au moins une liaison peptidique anormale comportant au moins une liaison peptidique anormale dans le cycle cyclisés autrement que par l'acide diamino-2,4 butanoïque
C07K 1/06 - Procédés généraux de préparation de peptides utilisant des groupes protecteurs ou des agents d'activation
C07K 1/04 - Procédés généraux de préparation de peptides sur des supports
Provided is a method for solid phase synthesis of Etelcalcetide, comprising synthesizing Etelcalcetide backbone peptide resin, removing the side chain protecting group of Cys in the peptide chain, and then activating the sulfydryl group of the Cys side chain on the peptide resin with 2,2′-dithiodipyridine and constructing a disulfide bond with L-Cys, such that a crude Etelcalcetide peptide is obtained by cleaving. The method does not require undergoing multi-step purification, the yield and purity of the obtained crude peptide are relatively high, and the total yield of the refined peptide after purification is greatly increased.
5 of the compound shown in formula II to obtain a compound of formula III; (3) carrying out condensation reaction on the compound shown in formula III and
to obtain a compound shown in formula I. The method reduces the time of deprotection, and all the reactions can be carried out in a solvent with low boiling point. The post-processing requires only simple washing and recrystallization to obtain the product with higher purity, so the method is suitable for large-scale production.
C07C 231/02 - Préparation d'amides d'acides carboxyliques à partir d'acides carboxyliques ou à partir de leurs esters, anhydrides ou halogénures par réaction avec de l'ammoniac ou des amines
B01J 31/00 - Catalyseurs contenant des hydrures, des complexes de coordination ou des composés organiques
C07C 231/14 - Préparation d'amides d'acides carboxyliques par formation de groupes carboxamide combinée avec des réactions n'impliquant pas les groupes carboxamide
C07C 269/06 - Préparation de dérivés d'acide carbamique, c.-à-d. de composés contenant l'un des groupes l'atome d'azote ne faisant pas partie de groupes nitro ou nitroso par des réactions n'impliquant pas la formation de groupes carbamate
C07C 231/12 - Préparation d'amides d'acides carboxyliques par des réactions n'impliquant pas la formation de groupes carboxamide
B01J 31/02 - Catalyseurs contenant des hydrures, des complexes de coordination ou des composés organiques contenant des composés organiques ou des hydrures métalliques
C07C 237/22 - Amides d'acides carboxyliques, le squelette carboné de la partie acide étant substitué de plus par des groupes amino ayant les atomes de carbone des groupes carboxamide liés à des atomes de carbone acycliques du squelette carboné ayant des atomes d'azote de groupes amino liés au squelette carboné de la partie acide, en outre acylés
C07B 41/12 - Formation ou introduction de groupes fonctionnels contenant de l'oxygène de groupes esters d'acides carboxyliques
C07B 43/06 - Formation ou introduction de groupes fonctionnels contenant de l'azote de groupes amide
C07C 235/08 - Amides d'acides carboxyliques, le squelette carboné de la partie acide étant substitué de plus par des atomes d'oxygène ayant des atomes de carbone de groupes carboxamide liés à des atomes de carbone acycliques et des atomes d'oxygène, liés par des liaisons simples, liés au même squelette carboné le squelette carboné étant acyclique et saturé ayant l'atome d'azote d'au moins un des groupes carboxamide lié à un atome de carbone acyclique d'un radical hydrocarboné substitué par des atomes d'oxygène liés par des liaisons simples
Disclosed is a method of synthesizing linaclotide through completely selective formation of three disulfide bonds, comprising the steps of: 1) synthesizing linaclotide precursor resin through solid-phase synthesis; 2) forming the first disulfide bond through solid phase oxidation; 3) forming the second disulfide bond through liquid phase oxidation; and 4) deprotecting methyl in the methyl-protected cysteine, and oxidatively coupling the third disulfide bond to obtain linaclotide. The method has mild reaction conditions with low cost, high yield and high purity product, is a simple and stable process and is suitable for large-scale production.
Provided is a preparation method for plecanatide, comprising the following steps: 1) sequentially couple Fmoc-AA-OH on a solid-phase synthetic resin; 2) remove a StBu protecting group on Cys; 3) remove a Cys oxidation ring of the StBu protecting group to obtain a monodisulfide ring-containing plecanatide precursor resin; 4) crack the solid-phase synthetic resin to prepare a monodisulfide ring-containing plecanatide precursor; 5) 3-Cl-Ala at potential 7 and potential 15 in the monodisulfide ring-containing plecanatide precursor form a disulfide bond to form a ring under the action of a vulcanized agent in a liquid phase reaction to obtain plecanatide.
The present invention provides a preparation method for ularitide, comprising the following steps: 1) sequentially coupling Fmoc-AA-OH on a solid-phase synthetic resin; 2) removing the resin with a lysis buffer; and 3) reacting an intermediate obtained in step 2) with sodium thiosulfate pentahydrate in a solvent at the reaction temperature of 25-100°C, and completely reacting to obtain ularitide. The method of the present invention is appropriate to industrial preparation, and the yield thereof is greatly improved relative to the efficiency and yield of the solid-phase synthetic method.
Provided are a rivaroxaban self-emulsifying preparation and a preparation method therefor, wherein the preparation comprises by mass percentage, 1 to 13% of rivaroxaban, 5 to 50% of oil phase, 20 to 70% of emulsifier, 0 - 50% of the coemulsifier; the preparation method therefor comprises mixing the oil phase, the emulsifier and the coemulsifier uniformly, and then mixing the mixture with rivaroxaban to obtain the rivaroxaban self-emulsifying preparation.
A61K 31/5377 - 1,4-Oxazines, p. ex. morpholine non condensées et contenant d'autres hétérocycles, p. ex. timolol
A61K 47/44 - Huiles, graisses ou cires couvertes par plus d’un des groupes Huiles, graisses ou cires naturelles ou naturelles modifiées, p. ex. huile de ricin, huile de ricin polyéthoxylée, cire de lignite, lignite, gomme-laque, colophane, cire d’abeille ou lanoline
A61K 47/14 - Esters d’acides carboxyliques, p. ex. acides gras monoglycérides, triglycérides à chaine moyenne, parabènes ou esters d’acide gras de PEG
A61P 9/14 - VasoprotecteursAntihémorroïdauxMédicaments pour le traitement des varicesStabilisateurs capillaires
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
A61P 11/00 - Médicaments pour le traitement des troubles du système respiratoire
71.
STABLE PHARMACEUTICAL COMPOSITION COMPRISING CARBETOCIN AND SUITABLE FOR VAGINAL ADMINISTRATION, AND PREPARATION METHOD THEREFOR
A pharmaceutical composition comprising carbetocin, comprising (percent by weight): 0.5%-7% of carbetocin, 1%-10% of a water-soluble matrix material, 0.5%-5% of an amino acid anionic surfactant, 0.1%-5% of a humectant, and the balance of water. The amino acid anionic surfactant in the pharmaceutical composition can effectively eliminate the clinical difference caused by the individual difference, can effectively and stably stimulate uterine contraction, and can maintain the stability of a drug.
Disclosed is a method for preparing sodium aescinate, relating to the technical field of plant extraction. The method comprises: semen aesculi is taken and subjected to alcohol extraction, the resulting extracting solution is subjected to extraction with chloroform, dichloromethane or ethyl acetate under acidic conditions, and the resulting aescine crude product is successively subjected to salifying, decoloring and acetone precipitation to obtain a sodium aescinate crude product: the sodium aescinate crude product is purified by high-performance liquid chromatography, aescine A, B, C and D are collected and combined to obtain an aescine mixture, wherein same is then further desalinized by high-performance liquid chromatography, and the aescine pure product is collected and salified to obtain the sodium aescinate pure product. The semen aesculi is subjected to extraction and primary purification by an organic solvent, the use of the existing long-lasting processes, such as using macroporous adsorption resins, is avoided, and HPLC deep purification and desalinization steps are carried out on this basis, thereby generally achieving the purpose of significantly shortening the purification cycle and improving the total yield of sodium aescinate, and thus improving the production efficiency of sodium aescinate.
The present invention relates to a pharmaceutical composition comprising an oxytocin analog, a preparation method therefor, and a use thereof. The pharmaceutical composition comprises an oxytocin analog, an excipient, and a divalent metal ion salt. The divalent metal ion salt is selected from a solution of one or more of calcium chloride, calcium acetate, calcium citrate, calcium tartrate, zinc chloride, zinc gluconate, calcium gluconate, calcium sulfate, zinc sulfate, zinc acetate, and zinc citrate. The pharmaceutical composition of the present invention can eliminate the difference in uterine sensitivity and can be stably stored for a long time at a temperature of 30ºC.
A61K 9/19 - Préparations médicinales caractérisées par un aspect particulier à l'état particulaire, p. ex. poudres lyophilisées
A61P 15/04 - Médicaments pour le traitement des troubles génitaux ou sexuelsContraceptifs pour le déclenchement de l'accouchement ou de l'avortementUtérotoniques
74.
High performance liquid chromatography method for polypeptide mixtures
The present invention relates to a high performance liquid chromatography method for polypeptide mixtures. Specifically, the method including the following steps: step (1): preparing a solution of the glatiramer acetate to be tested; step (2): performing gradient elution on a sample to be tested with an anion exchange liquid chromatography, a cation exchange liquid chromatography, or a reversed-phase liquid chromatography; step (3): determining a peak area corresponding to each component of the glatiramer acetate, comparing the peak area with to a peak area of a reference substance to determine whether the content of each component of the sample to be tested is in a qualified range.
G01N 1/18 - Dispositifs pour prélever des échantillons à l'état liquide ou fluide avec mesures prises pour diviser des échantillons en plusieurs parties
G01N 33/00 - Recherche ou analyse des matériaux par des méthodes spécifiques non couvertes par les groupes
G01N 30/34 - Contrôle des paramètres physiques du fluide vecteur de la composition du fluide, p. ex. du gradient
G01N 21/33 - CouleurPropriétés spectrales, c.-à-d. comparaison de l'effet du matériau sur la lumière pour plusieurs longueurs d'ondes ou plusieurs bandes de longueurs d'ondes différentes en recherchant l'effet relatif du matériau pour les longueurs d'ondes caractéristiques d'éléments ou de molécules spécifiques, p. ex. spectrométrie d'absorption atomique en utilisant la lumière ultraviolette
A61K 38/03 - Peptides ayant jusqu'à 20 amino-acides dans une séquence indéterminée ou partiellement déterminéeLeurs dérivés
C07K 14/00 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés
B01D 15/32 - Chromatographie en phase liée, p. ex. avec une phase normale liée, une phase inverse ou une interaction hydrophobe
B01D 15/36 - Adsorption sélective, p. ex. chromatographie caractérisée par le mécanisme de séparation impliquant une interaction ionique, p. ex. échange d'ions, paire d'ions, suppression d'ions ou exclusion d'ions
G01N 30/88 - Systèmes intégrés d'analyse, spécialement adaptés à cet effet, non couverts par un seul des groupes
G01N 33/68 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des protéines, peptides ou amino-acides
The present invention discloses a method for preparing glatiramer acetate, comprising: (1) dissolving L-alanine NCA, L-tyrosine NCA, L-glutamic acid-γ-benzyl ester NCA, and L-ε-trifluoroacetyl-lysine NCA in 1,4-dioxane as solvent, stirring until a clarified solution is formed; (2) adding diethylamine for catalysis, stirring at 20-25° C., then slowly pouring the reaction solution into water, collecting the produced white product; (3) adding the obtained product to a solution of hydrobromic acid in acetic acid, stirring at 23.0-25.0° C., pouring the reaction solution into purified water for quenching and stirring, subjecting the mixture to suction filtration to obtain a yellow solid, after repeating 3-5 times, subjecting the solid to blast drying to remove the moisture therein; and (4) dissolving the solid obtained in step (3) in a 1M piperidine aqueous solution at room temperature and stirring, subjecting the obtained solution to dialysis, adding glacial acetic acid to adjust the pH to 5.5-7.0, and lyophilizing.
C08G 69/36 - Polyamides dérivés, soit des acides amino-carboxyliques, soit de polyamines et d'acides polycarboxyliques dérivés d'aminoacides, de polyamines et d'acides polycarboxyliques
C07K 2/00 - Peptides à nombre indéterminé d'amino-acidesLeurs dérivés
76.
PHARMACEUTICAL COMPOSITION AND MANUFACTURING METHOD THEREOF
The present invention relates to the field of polypeptides and particularly provides a pharmaceutical composition and a manufacturing method thereof. The pharmaceutical composition comprises a liraglutide, and the manufacturing method of the pharmaceutical composition comprises: mixing, in a solvent, the liraglutide and an adjuvant, stirring the resultant mixture at 500-1100 rpm until homogeneous, and adjusting the pH to 7.5-9.5. Various manufacturing process parameters can influence the stability of liraglutide and may cause significant changes in oligomerization, single maximal impurity, and total impurity. The infrared spectrum shows an amide band I (at about 1645 nm-1), indicating the presence of an α-helix structure, with strong absorption and a basically consistent peak shape. The present invention controls, by examination of the secondary structure of a polypeptide, parameter screening of a pharmaceutical preparation process.
An ipragliflozin oral solid preparation can be in the dosage form of tablets, powders, or capsules and comprises an anti-adhesion agent, filler, and an optional disintegrant, binder, lubricant, and coating material. Correspondingly, also provided is a preparation method of the oral solid preparation. When the oral solid preparation is in the dosage form of tablets, the method comprises the steps of forming a premix, forming a medicated mixture, tableting, and coating. When the oral solid preparation is in the dosage form of capsules, the medicated mixture is filled into capsule shells. When the oral solid preparation is in the dosage form of powders, the medicated mixture is packaged in packaging containers.
Disclosed is a nasal gel composition of glatiramer acetate, wherein same is made from glatiramer acetate, a gel matrix and other pharmaceutically acceptable excipients. The other pharmaceutically acceptable excipients comprise from 0.9%-1.75 % of a bioadhesive material. The bioadhesive material is selected from a combination of one or more of starch, chitin, glucan and xanthan gum.
A61K 38/02 - Peptides à nombre indéterminé d'amino-acidesLeurs dérivés
A61K 47/36 - PolysaccharidesLeurs dérivés, p. ex. gommes, amidon, alginate, dextrine, acide hyaluronique, chitosane, inuline, agar-agar ou pectine
A61P 25/28 - Médicaments pour le traitement des troubles du système nerveux des troubles dégénératifs du système nerveux central, p. ex. agents nootropes, activateurs de la cognition, médicaments pour traiter la maladie d'Alzheimer ou d'autres formes de démence
Provided is a method for synthesizing a C-terminal modified peptide, comprising the following steps: 1) coupling an amine-terminus of a diamino compound to a resin to achieve a solid-phase synthesis; 2) successively coupling an amino acid to the other amine-terminus of the diamino compound using an Fmoc solid-phase peptide synthesis method to obtain a fully-protected polypeptidyl resin; 3) cleaving a fully-protected polypeptide from the resin to obtain the fully-protected polypeptide; 4) removing a protecting group from the fully-protected polypeptide to obtain the target C-terminal modified peptide, or 5) coupling the fully-protected polypeptide to a carboxyl-containing modifying group to obtain the target C-terminal modified peptide.
A method for detecting ganirelix acetate comprises: dissolving ganirelix acetate; by using a salt solution as an A phase of mobile phases and using a water solution of acetonitrile as a B phase of the mobile phases, performing detection by means of an HPLC method, so as to obtain a chromatogram; and obtaining the content of ganirelix acetate and the content of a by-product according to the chromatogram, the salt in the A phase of the mobile phases being selected from ammonium sulfate, sodium perchlorate, potassium dihydrogen phosphate and sodium dihydrogen phosphate. The detection method has high accuracy, high sensitivity and good repeatability, and the lowest detection limit of an effective component and a by-product in ganirelix acetate is lower than 40ng/mL.
The present invention relates to a method for preparing a long-chain compound, comprising the following steps: 1) performing a condensation reaction of H-R2 and R5N-Glu(OR4)-OR3, wherein R3 is a carboxyl protecting group, R4 is a carboxyl activating group, and R5 is an amino protecting group, to obtain a compound of formula II; 2) removing the R3 carboxyl protecting group and the R5 amino protecting group of the compound represented by formula II to obtain a compound of formula III; and 3) performing a condensation reaction between the compound represented by formula III and AA to obtain the compound represented by formula I. The method reduces numbers of deprotection times, and all the reactions can be performed in a low boiling solvent; the post-treatment only requires simple washing and recrystallization to obtain a product with a higher purity; and the method is suitable for large-scale production.
C07C 231/14 - Préparation d'amides d'acides carboxyliques par formation de groupes carboxamide combinée avec des réactions n'impliquant pas les groupes carboxamide
C07C 237/22 - Amides d'acides carboxyliques, le squelette carboné de la partie acide étant substitué de plus par des groupes amino ayant les atomes de carbone des groupes carboxamide liés à des atomes de carbone acycliques du squelette carboné ayant des atomes d'azote de groupes amino liés au squelette carboné de la partie acide, en outre acylés
82.
TERLIPRESSIN LIPOSOME AND PREPARATION METHOD THEREOF
Provided in the present invention is a terlipressin liposome, wherein the pH value of the internal water phase thereof is 7.9-8.9. Also provided is a method for preparing the terlipressin liposome.
A method for preparing Sermaglutide. Amino acid protected by Fmoc-Lys(Alloc)-OH is used as a raw material, and protection is carried out by selecting Pd(PPh3)4. In one aspect, the operation process is simple, one or two times of elimination reactions are required only, each time lasts 10 min to 30 min, and no side reaction occurs, and the operation process is safe, so that the preparation method is suitable for expanding production. The risk of His racemization can be reduced to the greatest extent in the process by using Boc-His(Boc)-OH.DCHA and Boc-His(Trt)-OH as raw materials. The synthesis efficiency is improved by performing coupling by using special segments.
C07K 14/435 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains
C07K 1/06 - Procédés généraux de préparation de peptides utilisant des groupes protecteurs ou des agents d'activation
C07K 1/04 - Procédés généraux de préparation de peptides sur des supports
A method for preparing Lixisenatide. According to a peptide sequence structure of Lixisenatide peptide, specially protected serine dipeptide is used as a raw material and coupled into a peptide sequence. Because of a ring-shaped structure similar to that of proline is formed, the rotation of a peptide bond can be effectively prevented, the contraction of a peptide chain curling agent is suppressed, so that active functional groups are fully exposed, thereby facilitating the coupling of the amino acid, and reducing the occurrence of defects and other side effects.
A dapagliflozin and metformin complex extended release tablet comprises a metformin hydrochloride tablet core, a dapagliflozin quick release layer, and a thin film layer. A preparation method of the dapagliflozin and metformin complex extended release tablet comprises: 1). preparing a tablet core comprising metformin; 2). packaging using a dapagliflozin quick release layer; and 3). packaging using a thin film layer.
A61K 31/351 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle non condensés avec un autre cycle
A61P 3/10 - Médicaments pour le traitement des troubles du métabolisme de l'homéostase du glucose de l'hyperglycémie, p. ex. antidiabétiques
Disclosed is a method for synthesizing etelcalcetide. The method involves synthesizing in a liquid phase a linear heptapeptide having the amino acid sequence as set forth in SEQ ID NO: 1, with the N-terminal end being acetylated and the C-terminal end being amidated; generating L-Cys(SCl) by subjecting L-Cys to chlorination with NCS such that the hydrogen in the sulfhydryl group is substituted by chlorine; and generating a disulfide by subjecting the heptapeptide and the L-Cys(SCl) to a coupling reaction, thus obtaining etelcalcetide. The method employs a completely liquid-phase process to synthesize etelcalcetide, which, in comparision to a solid-phase process, uses less reagents and solvents and is thus environmentally-friendly, and does not use costly resins and thus reduces the cost. Moreover, by generating a disulfide bond via an active intermediate formed by inexpensive and readily available NCS with cysteine, the disadvantages of low conversion rate and low purity associated with a conventional process are avoided, which facilitates large-scale production of etelcalcetide.
Provided is a solid phase synthesis method of Etelcalcetide, comprising synthesizing a Etelcalcetide backbone peptide resin, removing the side chain protecting group of Cys in the peptide chain, and then activating the sulfydryl of the Cys side chain on the peptide resin with 2,2'-dithiodipyridine and constructing a disulfide bond with L-Cys, such that the Etelcalcetide crude peptide is obtained by splitting decomposition. The method does not require undergoing multi-step purification, the yield and purity of the obtained crude peptide are relatively high, and the total yield of the pure peptide after purification is greatly increased.
The present invention provides a method for purifying and oxidizing polypeptide containing disulfide bond simultaneously. Specifically, the crude peptide on the chromatographic column is rinsed with mobile phase A and phase B, wherein the phase A contains an oxidizing agent for oxidizing disulfide bond, therefore, the disulfide bond is oxidized during the purification, and after the purification, the oxidized polypeptide is obtained.
C07K 14/435 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains
Disclosed is a method of synthesizing linaclotide through completely selective formation of three disulfide bonds, comprising the steps of: 1) synthesizing linaclotide precursor resin through solid-phase synthesis; 2) forming the first disulfide bond through solid phase oxidation; 3) forming the second disulfide bond through liquid phase oxidation; and 4) deprotecting methyl in the methyl-protected cysteine, and oxidatively coupling the third disulfide bond to obtain linaclotide. The method has mild reaction conditions with low cost, high yield and high purity product, is a simple and stable process and is suitable for large-scale production.
Provided is a completely-solid-phase preparation method for carbetocin, comprising: first, coupling chloro-butyric acid to tyrosine amino of a peptide chain through an amide coupling agent; and then, performing solid-phase cyclization by using DBU as a base to obtain a crude carbetocin peptide.
2-OH by employing Fmoc-Lys(Boc)-OH and Fmoc-D-Lys(Boc)-OH or Fmoc-Lys(Alloc)-OH and Fmoc-D-Lys(Alloc)-OH; synthesizing a ganirelix precursor I or ganirelix precursor II-peptide resin in advance; and then respectively performing modifications and treatments on side chain amino groups of Lys and D-Lys in the precursor I or the precursor II-peptide resin to obtain ganirelix acetate. The ganirelix acetate synthesized therefrom is high in purity, has few impurities and a relatively low cost, and is suitable for large-scale production.
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
05 - Produits pharmaceutiques, vétérinaires et hygièniques
10 - Appareils et instruments médicaux
35 - Publicité; Affaires commerciales
Produits et services
Protein [raw material]; industrial chemicals; biochemical
catalysts; chemical preparations for scientific purposes,
other than for medical or veterinary use; chemical reagents,
other than for medical or veterinary purposes; chemical
substances for preserving foodstuffs; biological
preparations, other than for medical or veterinary purposes;
plant growth regulating preparations; surface-active
chemical agents; synthetic resins, unprocessed. Chemico-pharmaceutical preparations; drugs for medical
purposes; medicines for human purposes; diagnostic
preparations for medical purposes; pharmaceutical
preparations containing active pharmaceutical ingredients;
enzymes for medical purposes; veterinary preparations;
vermin destroying preparations; biocides. Syringes for medical purposes; medical apparatus and
instruments; dental apparatus and instruments; physiotherapy
apparatus; cushions for medical purposes; suture materials;
condoms; contraceptives, non-chemical; orthopaedic articles;
babies' bottles. Retail or wholesale services for pharmaceutical, veterinary
and sanitary preparations and medical supplies.
93.
HIGH PERFORMANCE LIQUID CHROMATOGRAPHY METHOD FOR POLYPEPTIDE MIXTURES
Provided is a high performance liquid chromatography method for polypeptide mixtures. Specifically, the method comprises the following steps of (1) formulating a Glatiramer acetate solution to be tested; (2) subjecting the sample to be tested to gradient elution by way of anion exchange liquid chromatography, cation exchange liquid chromatography or reversed-phase liquid chromatography; and (3) detecting and analyzing peak areas corresponding to various components of the copolymer, and by means of comparison with a control, determining whether the content ranges of the various components in the sample to be tested are qualified.
A61K 38/16 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés
A61P 25/28 - Médicaments pour le traitement des troubles du système nerveux des troubles dégénératifs du système nerveux central, p. ex. agents nootropes, activateurs de la cognition, médicaments pour traiter la maladie d'Alzheimer ou d'autres formes de démence
Provided is a method for preparing eptifibatide, wherein the method comprises: obtaining an eptifibatide refined peptide solution; and obtaining and freeze-drying an eptifibatide refined peptide concentrate after rotary evaporation of the eptifibatide refined peptide solution, wherein the concentration of the eptifibatide refined peptide concentrate is 15-30 mg/ml and the temperature of rotary evaporation is 251° C.-35° C. The preparation method of the eptifibatide refined peptide solution is as follows: coupling Cys with a resin to obtain a Cys-resin; obtaining a polypeptide having a sequence as represented by SEQ ID NO: 1 by gradually coupling the Cys-resin with Pro, Trp, Asp, Gly, Har and Mpa; and obtaining the eptifibatide refined peptide solution through oxidation, cleavage, purification and transfer to salt.
Provided is a method for the preparation of glatiramer acetate, comprising: (1) dissolving L-alanine NCA, L-tyrosine NCA, L-glutamic acid-γ-benzyl ester NCA and L-ε-trifluoroacetyl-lysine NCA in a 1,4-dioxane solvent, and stirring until the system is clear; (2) adding diethylamine, stirring at 20-25°C, then slowing pouring the reaction solution into water, and obtaining white product; (3) adding the obtained product to a hydrobromic-acetic acid solution, stirring at 23.0-25.0°C, pouring the reaction solution into purified water after stirring for quenching, stirring, performing suction filtration to obtain a yellow solid, and after repeating 3-5 times, performing drying; (4) dissolving the solid with a 1M piperidine solution at room temperature and stirring, and after the obtained solution has undergone dialysis, adding glacial acetic acid to adjust the pH to be 5.5-7.0, and performing lyophilisation.
Disclosed is a method for preparing ganirelix acetate. The method comprises the following steps: respectively replacing Fmoc-HArg(Et) 2-OH and Fmoc-D-HArg(Et) 2-OH by employing Fmoc-Lys(Boc)-OH and Fmoc-D-Lys(Boc)-OH or Fmoc-Lys(Alloc)-OH and Fmoc-D-Lys(Alloc)-OH; synthesizing a ganirelix precursor I or ganirelix precursor II-peptide resin in advance; and then respectively performing modifications and treatments on side chain amino groups of Lys and D-Lys in the precursor I or the precursor II-peptide resin to obtain ganirelix acetate. The ganirelix acetate synthesized therefrom is high in purity, has less impurities and a relatively low in cost, and is suitable for large-scale production.
The present invention relates to a dabigatran etexilate synthesizing method, the method being characterized by: using 2-(hydroxymethyl)-1H-benzimidazole -5-carboxy acid as raw material, thus greatly reducing the raw material and reagent costs for synthesizing benzimidazole, and having considerable economic value and market competitiveness; and not discharging a great deal of waste acid in a reaction process, thus having environmental value, and providing an optimal solution for large-scale industrial production of dabigatran etexilate.
C07D 401/12 - Composés hétérocycliques contenant plusieurs hétérocycles comportant des atomes d'azote comme uniques hétéro-atomes du cycle, au moins un cycle étant un cycle à six chaînons avec un unique atome d'azote contenant deux hétérocycles liés par une chaîne contenant des hétéro-atomes comme chaînons
Disclosed is a method for synthesizing glatiramer acetate. The present method uses two or multiple depolymerization steps to control the average molecular weight of the glatiramer acetate product within a relatively narrow range.
C07K 14/00 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés
C07K 2/00 - Peptides à nombre indéterminé d'amino-acidesLeurs dérivés
C07K 1/06 - Procédés généraux de préparation de peptides utilisant des groupes protecteurs ou des agents d'activation
C07K 1/02 - Procédés généraux de préparation de peptides en solution
C07K 1/34 - ExtractionSéparationPurification par filtration, ultrafiltration ou osmose inverse
A61K 38/16 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés
A61P 25/28 - Médicaments pour le traitement des troubles du système nerveux des troubles dégénératifs du système nerveux central, p. ex. agents nootropes, activateurs de la cognition, médicaments pour traiter la maladie d'Alzheimer ou d'autres formes de démence
Provided is a method for preparing eptifibatide, wherein the method comprises: obtaining an eptifibatide refined peptide solution; and obtaining and freeze-drying an eptifibatide refined peptide concentrate after rotary evaporation of the eptifibatide refined peptide solution, wherein the concentration of the eptifibatide refined peptide concentrate is 15-30 mg/ml and the temperature of rotary evaporation is 251°C-35°C. The preparation method of the eptifibatide refined peptide solution is as follows: coupling Cys with a resin to obtain a Cys-resin; obtaining a polypeptide having a sequence as represented by SEQ ID NO: 1 by gradually coupling the Cys-resin with Pro, Trp, Asp, Gly, Har and Mpr; and obtaining the eptifibatide refined peptide solution through oxidation, cleavage, purification and transfer to salt.
Disclosed are a dulaglutide injection and the preparation method thereof, the injection containing: dulaglutide, a pH regulator, a solubilizer, an antimicrobial agent, an osmotic pressure regulator, and water for injection, wherein, in addition to water for injection, the content of each component by weight ratio is: dulaglutide:the pH regulator:the solubilizer:the antimicrobial agent: the osmotic pressure regulator 1.5:(2.0-35):(2-5): 7-16:(180-420), and the ratio of the total weight of these five components and the volume of the water for injection in mg/ml is 0.6-1.6.
