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Liposome nanometer carrier situ gel preparation used for eye epidermal growth factor

An epidermal growth factor and lipid nanocarrier technology, which is applied in the directions of liposome delivery, medical preparations containing active ingredients, peptide/protein ingredients, etc. Deformability, industrial production and filling inconvenience, etc., to achieve good physical and chemical stability, overcome rapid loss, easy and accurate dosage control effect

Inactive Publication Date: 2007-10-24
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Chinese patent CN1289619 reports a preparation method of epidermal growth factor eye drops. The preparation makes epidermal growth factor and related auxiliary materials into an aqueous solution, then makes a lyophilized powder and injects it into a solvent, although the preparation process maintains The activity of EGF, but still cannot avoid its slow degradation and loss of activity in aqueous solvent
U.S. Patent UP4944948 has reported a kind of EGF liposome gel preparation, can achieve the purpose of sustained release, but water-soluble EGF leaks easily, thus affects encapsulation efficiency and drug stability
Chinese patent CN1362883 and European patent EP0312208 respectively reported several ordinary gel preparations of epidermal growth factor, but the ordinary gel preparations have the following defects: ① large viscosity in vitro, poor fluidity, and inconvenient clinical application; ② preparation process It is easy to produce a large number of bubbles, which is inconvenient for industrial production and filling; ③ does not have pseudoplastic deformation, and the drug is not easy to spread evenly on the surface of the cornea and conjunctiva by blinking

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036]First, according to the composition of Example 1 given in Table 1 below, 0.1 mg EGF, 20 g MCT, 80 g glycerol monostearate, and 10 g soybean lecithin were dissolved in 100 ml ethanol solution, and the water bath was 50 ° C. Under high shear conditions (IKA, T25 basic type, 10,000rpm), add it into a 500ml ice-water bath and stir for 30min to obtain the EGF lipid nanocarrier suspension. Centrifuge at 20000rpm for 30min to obtain the carrier precipitate, and further disperse the carrier precipitate with 200ml deionized water.

[0037] Dissolve 0.5g gellan gum and 20g glycerin in 400ml deionized water, stir and dissolve at 40°C, add the dispersed carrier suspension, add 0.05g antibacterial agent benzalkonium chloride; the final concentration is 0.3M triethanolamine Adjust the pH of the solution to 6.2, make up to 1000ml with deionized water, and fill it.

Embodiment 2~4

[0039] Using the same preparation method as in Example 1, the lipid nanocarrier in-situ gel preparations in Examples 2-4 were prepared from the composition and process parameters given in Table 1.

[0040] Example 1

Embodiment 5

[0042] First, according to the composition of Example 5 given in Table 2 below, 10mg EGF, 6g soybean oil, 24g glyceryl monostearate, 30g soybean lecithin, and 15g polyoxyethylene castor oil are dissolved in 100ml ethanol solution, and the water bath is 50°C . Under high shear conditions (IKA, T25 basic type, 10,000rpm), add it into a 500ml ice-water bath and stir for 30min to obtain the EGF lipid nanocarrier suspension. Centrifuge at 20000rpm for 30min, and then use 200ml deionized water to disperse the carrier for precipitation.

[0043] Dissolve 1g Carbopol 1934, 15g MC, and 16g glycerin in 400ml deionized water, stir to dissolve at 40°C, add the dispersed carrier suspension, and then add 0.5g bacteriostatic agent benzalkonium chloride; then use 0.5M NaOH solution Adjust to pH 6.8; make up to 1000ml with deionized water, fill it, and get ready.

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PUM

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Abstract

The invention relates to a liposome nano carrier in-situ gelling preparation for eyes containing epidermal growth factor, which is prepared from epidermal growth factor, lipid material, emulsifying agent, thickening agent, isotonic conditioning agent, bacteria inhibitor, pH regulator and purified water, wherein non-irritating phosphatide is employed as the emulsifying agent, macromolecular material having ion and / or pH responsive characteristics is used as the thickening agent.

Description

technical field [0001] The invention relates to a gel preparation, in particular to an ophthalmic lipid nanocarrier in situ gel preparation containing human epidermal growth factor (hEGF). Background technique [0002] Epidermal growth factor is an important biological polypeptide growth factor containing 53 amino acids (Cohem, et al., J.Biol.Chem.248, 7669-7672, 1973), which has both mitogenic and non-mitogenic activities , can stimulate the proliferation and differentiation of ectoderm, mesoderm and endoderm cells, and promote tissue growth, development and maturation. EGF is one of the strongest cytokines in mammalian eyes. It can stimulate corneal epithelial cell proliferation, chemotaxis and migration in wound healing, so it can treat corneal epithelial defects and keratopathy caused by various reasons, mild to moderate dry eye, Corneal abrasions, mild to moderate chemical burns, corneal surgery and postoperative poor healing, corneal ulcers and bullous keratitis, etc....

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/18A61K9/127A61K9/00A61K47/44A61P27/02
Inventor 甘勇甘莉韩顺
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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