Glucagon-like peptide-1 analogue sustained release microsphere as well as preparation method thereof

A technology of glucagon and sustained-release microspheres, which is applied in the field of sustained-release preparations and preparations of glucagon-like peptide-1 analogues, and can solve the problem that microspheres cannot achieve the release effect, affect the therapeutic effect of the preparation, and cause blood Avoid problems such as increased drug concentration, achieve uniform size, reduce the number of administrations, and control blood sugar

Inactive Publication Date: 2018-08-24
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although there are many microsphere products on the market, there are still the following problems in the current microsphere technology: (1) due to the contact with organic solvents during the preparation process and the strong shear force in the emulsification process, it is easy to It will lead to the degradation and inactivation of the encapsulated polypeptide, thus affecting the therapeutic effect of the preparation
(2) The sudden release of microspheres is the most important problem in the clinical application of microspheres. Generally speaking, the effective therapeutic dose of peptides is very small. However, many experiments in vivo and in vitro have proved that PLGA sustained-release microspheres are the first The release within one day will have a relatively large burst release. This burst release will not only cause a sudden increase in blood drug concentration and bring certain side effects, but also cause a release plateau period for a period of time, so that the microspheres cannot achieve a sustained release effect and affect the formulation. Efficacy

Method used

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  • Glucagon-like peptide-1 analogue sustained release microsphere as well as preparation method thereof
  • Glucagon-like peptide-1 analogue sustained release microsphere as well as preparation method thereof
  • Glucagon-like peptide-1 analogue sustained release microsphere as well as preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0076] Accurately weigh 6 mg of GLP-1 analogue and dissolve it in 200 μl of water to configure an inner aqueous phase solution with a concentration of 30 mg / ml, and add the inner aqueous phase to 1 ml of polylactic acid polyglycolic acid (LA:GA= 50:50Mw=17kDa) in dichloromethane solution (oil phase), the volume ratio of the inner water phase to the oil phase is 1:5. The inner water phase is mixed with the oil phase, and ultrasonicated with a power of 50 W for 3 minutes in an ice-water bath to obtain a W / O emulsion. Slowly inject the obtained colostrum into 20ml of the external water phase containing 2% polyvinyl alcohol and 2.5% sodium chloride with a 25G syringe, and use a homogenizer to emulsify at a speed of 3000rpm for 1 minute to form a W / O / W double emulsion . Add the above-mentioned double emulsion to 200ml of 0.1% polyvinyl alcohol aqueous solution, solidify for 4 hours, and after the organic solvent is completely volatilized, centrifuge the suspension at 3000rpm for f...

Embodiment 2

[0078] Sprinkle 4mg of polypeptide lyophilized powder (S) into ethyl acetate solution (O) containing 1ml of 100mg / ml lactic acid polyglycolic acid (LA:GA=50:50Mw=17kDa), mix and use in an ice-water bath Sonicate the probe at 50W for 3 minutes to obtain the S / O suspension. Slowly inject the S / O suspension into 20ml of the external aqueous phase containing 2% sodium lauryl sulfate and 2.5% sodium chloride with a 25G syringe, and emulsify with a homogenizer at 3000rpm for 1 minute to form S / O / W lotion. Pour the above emulsion into 200ml of aqueous solution containing 0.1% PVA. After curing for 4 hours, after the organic solvent has evaporated completely, centrifuge the suspension at 8000rpm for five minutes, wash it with water for five times, and set it at 0.12MPa, -40 Freeze-dry at ℃. The obtained microspheres have an average particle size of 3.68 μm and a drug loading of 1.5%.

Embodiment 3

[0080]Accurately weigh 6 mg of GLP-1 analogue and dissolve it in 200 μl of water containing 10% PEG as a protective agent to form an internal aqueous phase solution with a polypeptide concentration of 30 mg / ml, and add the internal aqueous phase to 1 ml of polylactic acid poly(lactic acid) with a concentration of 100 mg / ml. In the chloroform solution (oil phase) of glycolic acid (LA:GA=50:50Mw=17kDa), the ratio of the inner water phase to the oil phase is 1:5. The inner water phase is mixed with the oil phase and ultrasonicated for 3 minutes using a probe ultrasonic method with a power of 50W in an ice-water bath to obtain a W / O emulsion. Slowly inject the obtained colostrum into 20ml of the external aqueous phase containing 2.5% polysorbate and 2.5% sodium chloride with a 25G syringe, and use a homogenizer to emulsify at a speed of 3000rpm for one minute to form a W / O / W complex milk. Pour the above double emulsion into, for example, 200ml of 0.1% polyvinyl alcohol aqueous so...

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Abstract

The invention discloses a glucagon-like peptide-1 analogue sustained release microsphere as well as a preparation method and an application thereof. The sustained release microsphere mainly includes 1-10 parts by weight of the glucagon-like peptide-1 analogue and 90-99 parts by weight of a polylactic acid-glycollic acid copolymer and is 0.5-100 [mu]m in range of average particle size. The invention also discloses the preparation method and the application of the sustained release microsphere and also inspects appearance, particle size, in-vitro releasing and in-vivo pharmacodynamic experimentof the microsphere. The sustained release microsphere supporting GLP-1 analogue has uniform particle size and has significant treatment effect on diabetes, can effectively control blood glucose for 14days and has the effect as a slow-effect preparation. The sustained release microsphere greatly reduces dosing frequency and increases compliance of patients, and also can inhibit food intake. The preparation method has simple process and gentle conditions, and is low in influence on activities of polypeptides.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to a slow-release preparation of glucagon-like peptide-1 analogue and a preparation method thereof. The slow-release preparation can release medicine for a long period of time to control blood sugar. Background technique [0002] Diabetes mellitus is a group of metabolic diseases characterized by chronic hyperglycemia caused by genetic and environmental factors. According to statistics, there were about 246 million diabetic patients in the world in 2007, and it will reach 380 million in 2025. Therefore, diabetes is a disease that seriously threatens human health. In the current clinical treatment, blood sugar is mainly controlled by injecting insulin and oral hypoglycemic drugs. However, these therapeutic drugs either have no obvious hypoglycemic effect, or are prone to relatively large side effects and poor patient compliance. With the advancement of medicine, the discover...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/50A61K47/34A61K38/26A61K47/52A61P3/04A61P3/10
CPCA61K9/5031A61K38/26A61K47/52A61P3/04A61P3/10
Inventor 蔡挺金亮阮思达
Owner CHINA PHARM UNIV
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