365 results about "Methionine biosynthesis" patented technology

There is provided a fluorinase variant thereof having at least 70% sequence identity to a sequence MSDLGX6TDDSVAQCKGLMLSICPX24VX26IX28DX30CHX33MTPX37DVVEGARYIVDLPR X52FPEGTVFATTTYPATGTX70X71RSVAX76RX78KX80AALGGARGQX90AGSGX95GX97E RAEGX103YIYIAPNNGLLTX116VIEEHGYX124EAYEVSX131TX133VIPX137X138PEPTFYSR EMVAIPSAHLAAGFPLX163X164VGRX168LX170DX172EIVRFEX179X180KX182X183X184VX186G X188X189LX191GX193X194X195X196X197DHPFGNX204WTNX208HRTDLEKAGIX219YX221TX223X 224KX226VX228DGVLX233FX235LPLX239PTFADAX246X247X248GX250PVX253YX255NSRGYLX2 62X263ARNAAX269LAYPYNLX277AGX280SVX283VTX286A (SEQ ID NO: 1), wherein X is a natural amino acid, and wherein the variant comprises one or more mutations at a site selected from the group consisting of an ion-egress site, a S-Adenosyl-L-Methionine (SAM) binding site, an ion-binding site (IBS), and a conserved site. Also disclosed are polynucleotides encoding the variants, vectors comprising the polynucleotides encoding the variants, and host cells comprising the vectors thereof. Also disclosed are Methods for producing the variants, methods of catalyzing the fluorination of a compound, uses of the fluorinase variants, and methods of treatment using the fluorinase variants thereof.

The invention discloses a high-stability carbonyl reductase mutant and application of the high-stability carbonyl reductase mutant in chiral alcohol synthesis. An amino acid sequence as shown in SEQ ID NO.2 is mutated as follows: 20th leucine is replaced by any one of lysine, threonine, aspartic acid or isoleucine, and / or 55th leucine is replaced by any one of methionine, serine, lysine or isoleucine, and / or 55th leucine is replaced by any one of methionine, serine, lysine or isoleucine. Compared with a wild type enzyme, the stability of the obtained mutant is remarkably improved, particularly, single-point mutants Mut-L20I and Mut-L55I and a combined mutant Mut-L20I-L55I show excellent relative enzyme activity, thermal stability and substrate tolerance. The mutant has high catalytic activity and stability to various chiral alcohols, has the advantages of high catalytic efficiency, high thermal stability, strong substrate tolerance, easiness in fermentation production and the like, and is suitable for industrial application of enzymatic synthesis of chiral alcohols.

The invention relates to the field of plant molecular biology and forest genetic engineering, and particularly provides a PagRAP2.3 protein point mutant and application thereof in drought resistance of poplar. The mutant PagRAP2.3 MA is obtained by mutating methionine at the first site and cysteine at the second site of a wild type PagRAP2.3 protein into methionine and alanine. The invention further discloses a preparation method of the mutant PagRAP2.3. An expression vector containing the PagRAP2.3 MA gene is constructed, poplar 84K is transformed through an agrobacterium-mediated method, and a transgenic line with stable expression is obtained. Functional verification results show that overexpression of PagRAP2.3 MA can significantly increase the plant height of the poplar and promote plant growth, but the sensitivity to moisture is enhanced under drought stress. The mutant can be used for regulating and controlling the growth and development of forest trees and evaluating the drought resistance, and has a forestry breeding application prospect.

The present application relates to a pyridoxal kinase mutant, a recombinant expression vector and a microbial cell and their applications, and belongs to the technical field of biological catalysis. In order to solve the problem of low product concentration in existing enzyme catalysis, a pyridoxal kinase mutant is provided, the amino acid sequence is selected from the amino acid sequence shown in SEQ ID NO. 1, the lysine at position 229 is mutated to alanine, phenylalanine, methionine, arginine, threonine, histidine, serine, tyrosine, valine, leucine, isoleucine, proline, asparagine, aspartic acid or glutamic acid; the pyridoxal kinase mutant is used for catalyzing pyridoxal to synthesize pyridoxal phosphate, and a recombinant expression vector and a microbial cell can be further formed. The present application has good enzyme activity, high product conversion rate, high concentration of pyridoxal phosphate obtained, and the concentration of the product catalyzed by the wild-type pyridoxal kinase to phosphorylate pyridoxal is obviously improved.

The invention belongs to the technical field of biological detection, and particularly relates to a method for synchronously and quantitatively detecting various folic acid metabolism related substances in trace plasma or serum, which comprises the following steps of: detecting a pretreated trace plasma or serum sample by adopting a liquid chromatography-tandem mass spectrometry method; the following nine folic acid metabolism related substances are synchronously and quantitatively detected: 5-formyl tetrahydrofolic acid, folic acid, 5-methyl tetrahydrofolic acid, S-adenosine-L-methionine, S-adenosine-L-homocysteine, vitamin B12, pyridoxamine, pyridoxine and pyridoxal. The invention further relates to application of the detection method in related detection of child neurodevelopment. According to the detection method, only trace plasma or serum is used, methotrexate is used for replacing an expensive isotope internal standard for more economical detection, and nine folate metabolism related substances can be accurately quantified at the same time. Therefore, the detection method disclosed by the invention has important clinical significance and wide market application prospect.

The invention discloses a chitosanase mutant which is derived from bacillus subtilis and has the capacity of hydrolyzing chitosan to produce chitosan disaccharide per unit and belongs to a GH46 family, and application of the chitosanase mutant in hydrolyzing chitosan to produce chitosan oligosaccharide. Compared with wild type chitosanase capable of producing chitodisaccharide and chitotriose, the chitosanase mutant has the advantage that the chitodisaccharide can be produced per unit when the chitodisaccharide is hydrolyzed by the chitosanase mutant. The invention provides eight kinds of chitosanase mutants, and the mutants are obtained by carrying out site-specific mutagenesis on 21st-site glycine on the basis of wild type chitosanase and respectively mutating the 21st-site glycine into lysine, arginine, leucine, histidine, methionine, tyrosine, proline and glutamine. The mutant can hydrolyze chitosan under mild conditions to produce chitosan oligosaccharide with single polymerization degree, and can greatly relieve the difficulty in separation and purification in chitosan oligosaccharide production.

The invention discloses a method for improving the fermentation performance of clostridium aerovorans and application of the clostridium aerovorans, and according to the method, an effective amount of methionine or a derivative thereof is added into a fermentation culture medium of the clostridium aerovorans to completely replace expensive complex organic nitrogen sources such as yeast extracts. The method successfully solves the three technical bottlenecks of slow biomass accumulation, low ethanol yield and dependence on expensive nitrogen sources in the fermentation process of the clostridium aerovorans by utilizing synthesis gas or CO2 / H2 mixed gas. Experiments prove that methionine or a derivative thereof can synergistically promote growth metabolism of thalli and a synthesis path of a product, so that the gas conversion efficiency of a carbon source is remarkably improved and metabolism is guided to flow to ethanol synthesis while the growth rate and the final biomass of the thalli are improved, and thus the production capacity of alcohols is synchronously enhanced. The method is simple in process and remarkable in effect, and an efficient and economical new strategy is provided for reducing the production cost of biofuel and promoting industrial application of a synthesis gas biorefinery technology.

The invention provides an application of synbiotics in preparation of a composition for improving glucagon-like peptide-1 (GLP-1). The composition comprises litchi polyphenol, probiotics and methionine. The probiotics comprise bifidobacterium animalis BCRC910645, bifidobacterium longum BCRC910812, or a combination of the bifidobacterium animalis BCRC910645 and the bifidobacterium longum BCRC910812, so that the content of the glucagon-like peptide-1 is increased.

The invention provides a recombinant O-succinyl-L-homoserine mercaptotransferase mutant, a coding gene thereof, a recombinant vector containing the coding gene of the mutant, a recombinant genetically engineered bacterium obtained by converting the recombinant vector, and application of the recombinant O-succinyl-L-homoserine mercaptotransferase mutant in preparation of L-methionine. The novel recombinant O-succinyl-L-homoserine mercaptotransferase mutant with high activity and high selectivity is used as a catalyst to be applied to catalysis of O-succinyl-L-homoserine for synthesis and preparation of L-methionine, a catalytic reaction system is optimized, the feed ratio and reaction conditions in the reaction are finely regulated and controlled, and the yield of L-methionine is increased. The recombinant O-succinyl-L-homoserine mercaptotransferase mutant has high enzyme activity under the optimal reaction condition, the catalytic efficiency is further improved, the purposes of reducing cost and improving efficiency are achieved, and the method has important significance in promoting industrial application of biological catalysis preparation of L-methionine.

The invention relates to the technical field of biological medicines, and discloses application of methionine adenosine transferase 2A and related substances thereof in preparation of wound repair products. According to the application disclosed by the invention, a metabolic regulation network in a diabetic wound surface is researched, so that MAT2A expression down-regulated in pericytes is found to be remarkably and negatively correlated with M1 type macrophage infiltration, and the situation that the wound healing is delayed, the wound surface blood perfusion is reduced and the inflammation macrophage infiltration is increased due to MAT2A specific deletion of the pericytes in the wound is observed; and after saMAT2A-loaded pericellular membrane coated lipid nanoparticles (PMCNPs) are further adopted for treatment, the regeneration process of the wound surface can be remarkably enhanced, continuous inflammatory macrophage infiltration in the diabetic wound surface is relieved, microcirculation recovery is promoted, the safety is high, and good application prospects are achieved in the aspect of promoting wound surface repair.

The invention relates to aspartate kinase for relieving feedback inhibition of L-threonine and application of aspartate kinase, and belongs to the field of enzyme engineering and metabolic engineering. The mutant is obtained by carrying out E253K and / or K507E mutation on the basis of wild type aspartate kinase as shown in SEQ ID NO.1, the enzyme activity of the mutant is not obviously changed under the condition that the concentration of L-threonine is 0-12 mmol / L, and the feedback inhibition effect of L-threonine on the mutant is relieved. The method can be widely applied to synthesis of essential amino acids including L-threonine, L-tryptophan, L-isoleucine, L-lysine, L-leucine, L-valine, L-methionine, L-phenylalanine and the like.

An Fc-binding polypeptide with improved alkaline stability comprising a mutant of the Fc-binding domain of Staphylococcus protein A (SpA), said mutant being defined by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 22, SEQ ID NO 51 or EQ ID NO 52, wherein at least the asparagine or serine residue at a position corresponding to position 11 in SEQ ID NO: 4-7 has been mutated to an amino acid selected from the group consisting of glutamic acid, lysine, tyrosine, threonine, phenylalanine, leucine, isoleucine, tryptophan, methionine, valine, alanine, histidine and arginine.

The application discloses application of a combined inhibitor in associated gold-silver-lead-zinc sulfide ore flotation separation, wherein the combined inhibitor is a combination of zinc sulfate and methionine, and the mass ratio of the two combined is 2:1; the combined inhibitor is used to realize associated gold-silver-low-copper-lead-zinc polymetallic sulfide ore flotation separation in a low-alkali environment, has a good separation effect, high concentrate grade, effectively reduces the zinc content of lead concentrate, improves the gold and silver recovery rate in the lead concentrate, and has important significance for improving the quality and efficiency of associated gold-silver-low-copper-lead-zinc polymetallic sulfide ore flotation separation. In addition, the methionine in the combined inhibitor is a small-molecule organic substance, is non-toxic and non-polluting, and is easy to degrade, thereby avoiding the problems of traditional inhibitors, such as toxicity, environmental unfriendliness and human body unfriendliness. The combined inhibitor has small dosage, stable effect, and good process application prospect.

The invention relates to a protein consisting of an amino acid sequence in which at least one modification selected from the group consisting of the following [1] to [7] is introduced in the amino acid sequence represented by SEQ ID NO: 1: [1] a modification in which the amino acid residue at a position 103 is substituted with a lysine residue, [2] a modification in which the amino acid residue at a position 76 is substituted with a cysteine residue, [3] a modification in which the amino acid residue at a position 144 is substituted with a cysteine residue, [4] a modification in which the amino acid residue at a position 134 is substituted with a glycine residue, [5] a modification in which the amino acid residue at a position 222 is substituted with a methionine residue, [6] a modification in which the amino acid residue at a position 73 is substituted with a glutamine residue, and [7] a modification in which the amino acid residue at a position 203 is substituted with a threonine residue.

The invention belongs to the technical field of enzyme gene engineering, and particularly relates to a methionine gamma-lyase mutant with improved enzyme activity and application thereof. The methionine gamma-lyase mutant CqMGLV160I / V265I with high activity is obtained by taking methionine gamma-lyase (CqMGL) which is derived from Calorama quimayensis and of which cysteine residues at 116 sites are replaced by histidine residues as a parent and carrying out site-specific mutagenesis on amino acid residues at key sites through transformation. The methionine gamma-lyase mutant CqMGLV160I / V265I with high activity can be obtained by using the methionine gamma-lyase mutant CqMGLV160I / V265I as the parent. By adopting the CqMGLV160I / V265I mutant disclosed by the invention, the conversion rate of enzyme catalysis can be improved, allicin is efficiently synthesized, and the mutant is successfully applied to the aspects of food, feed, chemical industry, medicine preparation and the like.

The application belongs to the technical field of preparation and application of spermidine, and particularly relates to application of fusarium NF01 in preparation of spermidine and catalysis of lignite liquefaction. The fusarium NF01 is fusarium strain Fusarium sp. NF01. The application finds that the fusarium strain Fusarium sp. NF01 can secrete spermidine synthetase, and then catalyze putrescine and decarboxylated S-adenosyl methionine to biosynthesize spermidine through the spermidine synthetase, so that the spermidine acts on lignite, and then the lignite is liquefied, which can promote the technical progress and application expansion in the field of coal development.

The present invention concerns the recovery of methionylmethionine from aqueous alkali ions containing media by intermediate formation of Bis(methionyl)-diketopiperazine.

The invention provides a dipeptide capable of rapidly supplementing methionine and application thereof, and belongs to the field of nutritional and functional food. The problems of quickly supplementing methionine and promoting lactation are solved. The preparation method comprises the step of preparing the dipeptide GM of which the C terminal is methionine through solid-phase synthesis. The dipeptide GM can be used for supplementing methionine, and it is verified that compared with EM, KM and MM, the dipeptide GM has the higher methionine absorption rate in cells based on the PepT1 vector. The dipeptide GM can also be used for promoting lactation, and it is verified that the dipeptide GM has a better lactation promoting effect compared with EM, KM and MM.

The present invention relates to the technical field of genetic engineering. Provided is a method for constructing an efficient zearalenone-degrading enzyme in the gastric environment of a pig. In the zearalenone-degrading enzyme as shown in SEQ ID NO: 1 that is taken as the parent, the amino acid at position 92, the amino acid at position 114, the amino acid at position 117, the amino acid at position 140, the amino acid at position 153, the amino acid at position 157 and the amino acid at position 220 are respectively mutated into lysine, leucine, tryptophan, arginine, methionine, valine and tryptophan to obtain the mutant. The obtained zearalenone-degrading enzyme mutant has high enzymatic activity and thermal stability, and is better adapted to the internal environment of pigs.

The present invention relates to a cosmetic composition, advantageously an eco-biological cosmetic composition, comprising: - polyglutamic acid or a salt thereof; and - at least one peptide derivative represented by the general formula (I) in which: - R1 represents a hydrogen atom, an acyl radical or an acyloxy radical; and - R2 represents the side chain of an alpha-amino acid chosen from the group consisting of phenylalanine, glutamic acid, arginine, cysteine, methionine, histidine and tyrosine. The present invention also relates to the use of said cosmetic composition for combating skin redness and / or skin aging; to its use for preventing and / or combating cutaneous vascular hyperproliferation and / or cutaneous inflammation and / or rosacea; and to a method for selecting compounds suitable for preventing and / or combating these pathologies.

The technology described herein is directed to compositions and methods for reducing levels of methionine. In various aspects described herein are: engineered methionine-reducing probiotic microorganisms; engineered methanethiol-reducing probiotic microorganisms; and engineered taurine-producing probiotic microorganisms. Also described herein are methods of using such engineered microorganisms, such as for reduction of bioavailable methionine or for treatment of a methionine-associated disease or disorder. Also described herein are probiotic dietary supplements, pharmaceutical compositions, and food compositions comprising such engineered microorganisms.

The present invention relates to an antibody or binding fragment thereof that binds to a protein, preferably a T cell receptor, comprising an epitope comprising or consisting of an amino acid sequence having at least 80 %, such as 83 %, preferably at least 90 %, for instance 100 % sequence identity to the amino acid sequence set forth in SEQ ID NO: 62 (EVPKXiR), wherein Xi is selected from Alanine (A), Arginine (R), Asparagine (N), Aspartic acid (D), Cysteine (C), Glutamine (Q), Glutamic acid (E), Glycine (G), Histidine (H), Isoleucine (I), Leucine (L), Lysine (K), Methionine (M), Phenylalanine (F), Proline (P), Serine (S), Threonine (T), Tryptophan (W), Tyrosine (Y), Valine (V). Further, the invention relates to pharmaceutical compositions comprising such an antibody or binding fragment thereof and to the use of such an antibody or binding fragment thereof for use as a medicament or for use as a screening agent.

The present invention relates to a compound, the compound is a compound represented by a formula (I), or an isomer, an isotope derivative, a polymorphic substance, a prodrug, a pharmaceutically acceptable salt or a solvate thereof, and the definitions of A1, B1 and L are the same as the definitions in the specification. Also provided are pharmaceutical compositions and compounds of formula (I) for use in methods of treating related diseases by inhibition of MAT2A, including some cancers in which a gene encoding a methylthioadenosine phosphorylase (MTAP) is deleted and / or not fully functioning.

A collagen-boosting supplement that contains at least 4, optionally at least 10, collagen building block amino acids and is substantially free of histidine. The building block amino acids may be selected from: Glycine, L-Proline, L-Hydroxyproline, L-Glutamic Acid, L-Alanine, L-Arginine, L-Aspartic Acid, L-Serine, L-Leucine, L-Lysine, L-Hydroxylysine, L-Valine, L-Phenylalanine, L-Threonine, L-Isoleucine, L-Methionine, and L-Tyrosine. The supplement may further comprise: vitamin C; one or more mast cell stabilisers which may be selected from: quercetin, molybdenum, bromelain, DAO (diamine oxidase), Urtica Dioica (stinging nettle), Nigella Sativa (black cumin), Zingiber (ginger), Scutellaria baicalensis (Chinese skullcap), Sambucus (Elderberry), Aloe Vera, Syzygium aromaticum (clove), and matcha; one or more collagen-strengthening herbs which may be selected from: Bilberry, Centella, and Astragulus; one or more Glucosaminoglycans (GAGs) which may be selected from: Hyaluronic acid, glucosamine, and chondroitin; one or more antioxidants which may be selected from: astaxanthin and resveratrol; and / or one or more cofactors which may be selected from: zinc, biotin, silicon, manganese, magnesium, Vitamin D, Vitamin A, Vitamin E, and iron. The supplement may be a foodstuff, medicament, nutraceutical, or cosmetic. The supplement may be used to treat hypermobile Ehlers-Danlos syndrome (hEDS) while reducing the likelihood of mast cell degranulation through histamine activation.

The present invention provides a method for preparing and applying amino acid-derived carbon dot nanozymes, belonging to the field of new biomedical materials technology. The amino acid comprises one of histidine, proline, cysteine, tryptophan, aspartic acid, arginine, lysine, methionine, and phenylalanine; the mass ratio of the amino acid to citric acid monohydrate is 1:1 to 1:5. The amino acid-derived carbon dots proposed in the present invention have free radical scavenging activity and superoxide dismutase-like properties, exhibiting low toxicity and good biosafety at the cellular, nematode, and animal levels. Furthermore, the amino acid-derived carbon dot nanozymes exhibit excellent anti-inflammatory activity, downregulating cellular inflammation, reducing oxidative stress damage to nematodes, improving intestinal flora structure, increasing the richness and diversity of intestinal flora, and alleviating and treating DSS-induced ulcerative colitis in mice. The nanozymes can be further applied to the preparation of drugs for treating inflammatory bowel disease.

The application provides a method for preparing cross-linking enzyme based on a tyrosinase mutant, the cross-linking enzyme and application thereof. The tyrosinase mutant is mixed with an ultrasonic broken solution of S-adenosylmethionine synthetase containing a tyrosine tag to obtain water-insoluble cross-linking enzyme particles, the cross-linking enzyme is collected by centrifugation or filtration and the like, and enzymatic conversion is carried out. It is found that the cross-linking enzyme of S-adenosylmethionine synthetase can be continuously and stably used for 6 batches, and the activity retention is 85%. The cross-linking enzyme particles prepared by the method have the characteristics of easy recovery, reusability and low cost, and have good industrial application value.

The present invention relates to peptide conjugates that comprise a plant-derived oligopeptide capable of crossing the blood-brain barrier (BBB) and a therapeutic or diagnostic agent. The BBB-penetrating oligopeptide is an oligopeptide according to Formula I, Asp–R2–Gly–Leu–R5–R6–R7–Leu–Gly–R10–R11–R12, wherein R2 represents Arg, Lys, Cyt, D-Arg or Orn; R5 represents Phe, Arg, Lys, His, Trp, Tyr, D-Tyr, D-Phe, Orn, 4-aminophenylalanine or 3-phenylpropionate; R6 represents Pro, Leu, Glu or Lys; R7 represents Phe or Trp; R10, R11 and R12 each independently represent Lys, Arg or Orn; or an oligopeptide according to Formula II, Glu–R2'–R3'–Gly–R5'–R6'–Glu–R8'–R9'–R10'–Glu–R12'–Leu–Pro–Gly, wherein R2', R3', R8', R10' and R12' each independently represent Lys, Arg or Orn; R5' represents Phe, Ile, Arg, Lys, His, Trp, Tyr, D-Tyr, D-Phe, 4-aminophenylalanine, or 3-phenylpropionate; R6' represents Met, Leu, Ile, Asn, norleucin, D-norleucin, seleno- methionine or D / L-2-hydroxy-(4-methylseleno)butanoic acid; and R9' represents Leu or Ile. The conjugates comprising a BBB-penetrating oligopeptide compound and a therapeutic agent can be used in treatments for diseases of the central nervous system (CNS). Furthermore, conjugates with a BBB-penetrating oligopeptide compound and a diagnostic agent can be used in both in vivo and in vitro diagnostic methods.

The application discloses a high-temperature-resistant alkaline alpha-galactosidase mutant and a preparation method thereof. The mutant is obtained by performing site-directed mutation on alpha-galactosidase derived from Anoxybacillus vitaminiphilus, and at least one amino acid in three positions of 444th, 457th and 509th in the amino acid sequence shown in SEQ ID No. 1 is replaced. The asparagine Asn in the 444th position is mutated into phenylalanine Phe, the aspartic acid Asp in the 457th position is mutated into methionine Met, and the arginine Arg in the 509th position is mutated into tryptophan Trp. The alpha-galactosidase mutant has good thermal stability and alkali stability by performing site-directed mutation on alpha-galactosidase derived from Anoxybacillus vitaminiphilus (Anoxybacillus vitaminiphilus WMF1).

The invention relates to a preparation of an antibody drug, which belongs to the field of biological medicines, is used for a preparation of a high-concentration antibody drug with an anti-oxidation requirement, and also has an anti-degradation capability. The preparation contains 20 mmol / L to 30 mmol / L of L-methionine and 200 mmol / L of trehalose, and is particularly suitable for being used for preparing Jukoulikumab, omaszumab and cetuximab. The preparation not only has a better anti-oxidation effect, but also can realize a synergistic stabilization effect by combining high-concentration L-Met with 200 mM trehalose, has anti-degradation ability, is widely applicable to various therapeutic antibodies, and provides an extensible solution for improving the stability and shelf life of a high-concentration biological preparation.

This invention relates to the field of lyophilized formulation technology, specifically disclosing an esupagglutide α-nano-lyophilized micelle and its preparation method. The micelles of this invention utilize polylactic-co-hydroxyacetic acid copolymer and sodium phosphatidylglycerol as micelle carriers, with arginine and cysteine ​​providing branching synergistic effects. Homogenization via film formation and low-temperature lyophilization yield lyophilized nano-micelle powder. The nano-micelle powder reduces protein oxidative decomposition during lyophilization, decreases impurity fragments, and reduces various non-fucose glycosylation, basic components (succinimide, methionine oxidation products), N-terminal deletion, Asn deamidation, and Met and Trp residue oxidation impurities that affect product quality. Product quality analysis and animal experiments after reconstitution show good resistance to impurities and degradation risk. The reconstituted esupagglutide α-nano-micelle system exhibits better stability and sustained-release properties, enhancing the hypoglycemic sustained-release effect 72 hours after injection, significantly improving upon conventional non-micelle formulations.