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A peptide-based osteoblast targeting carrier and its preparation and application

An osteoblast-targeted technology, applied in medical preparations with non-active ingredients, medical preparations containing active ingredients, bone diseases, etc., can solve potential toxicity and carcinogenicity, can not eliminate biological effects, very Difficult to eliminate and other problems, to achieve the effects of clear biomineralization ability, low production cost, strong plasticity and low toxicity

Inactive Publication Date: 2019-04-02
TONGJI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] As an antibacterial drug, tetracycline is used as a bone-targeted target, which cannot eliminate its own biological effects, and has side effects that lead to limited effects; the bone-targeted delivery system constructed from bisphosphonates can be used on the bone surface and dentin. Surface enrichment, difficult to rule out; growth factors have natural bone tropism, but short half-life, variability, and excessive application may have potential toxicity and carcinogenicity and other disadvantages

Method used

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  • A peptide-based osteoblast targeting carrier and its preparation and application
  • A peptide-based osteoblast targeting carrier and its preparation and application
  • A peptide-based osteoblast targeting carrier and its preparation and application

Examples

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Embodiment 1

[0046] An osteoblast targeting carrier constructed based on a polypeptide, the targeting carrier includes a target head and a scaffold, and the target head and the scaffold are covalently connected to the target head and the scaffold through polyethylene glycol carboxylic acid (PEG-COOH). The mass coverage rate of the target head is about 6%, and the molar coverage rate of the target head is 3%. The target head is a polypeptide composed of serine and aspartic acid, wherein the sequence of the polypeptide is Ser AspSer Ser Asp, wherein Ser represents serine and Asp represents aspartic acid; the scaffold is a polyurethane scaffold.

[0047] The above-mentioned targeting carrier, its synthesis method is as follows: figure 1 shown, including the following steps:

[0048] (1) Preparation of the target head: using a twelve-channel semi-automatic peptide synthesizer, the target head was synthesized by using the amino acid condensation sequence connection method, and serine (Fmoc-Asp...

Embodiment 2

[0059] An osteoblast targeting carrier constructed on the basis of polypeptides, the targeting carrier includes a target head and a scaffold, and the target head and the scaffold are covalently connected through polyethylene glycol carboxylic acid (PEG-COOH). The mass coverage rate of the target head is about 5%. The target head is a polypeptide composed of serine and aspartic acid, wherein the sequence of the polypeptide is Ser Asp, wherein Ser represents serine, and Asp represents aspartic acid; the scaffold is a polyurethane scaffold.

[0060] The synthesis method of the above-mentioned targeting carrier, for example, comprises the following steps:

[0061] (1) Preparation of the target head: using a twelve-channel semi-automatic peptide synthesizer, the target head was synthesized by using the amino acid condensation sequence connection method, and serine (Fmoc-Asp(otBu)-OH) and aspartic acid (Fmoc-Ser(Tbu) )-OH) is connected in the order of Ser-Asp to obtain the target h...

Embodiment 3

[0067] An osteoblast targeting carrier constructed based on a polypeptide, the targeting carrier includes a target head and a scaffold, and the target head and the scaffold are covalently connected through polyethylene glycol carboxylic acid (PEG-COOH). The grafting rate of the target head mass is about 6%. The target head is a polypeptide composed of serine and aspartic acid, with a length of 20 amino acids, wherein the sequence of the polypeptide is Ser Asp Asp Asp AspSer Asp Asp Asp Asp Ser Asp Asp Asp Asp Ser Asp Asp Asp Asp(Ser:Asp= 1:4), wherein, Ser represents serine, Asp represents aspartic acid; the scaffold is a polyurethane scaffold.

[0068] The synthesis method of the above-mentioned targeting carrier, for example, comprises the following steps:

[0069](1) Preparation of the target head: using a twelve-channel semi-automatic peptide synthesizer, the target head was synthesized by using the amino acid condensation sequence connection method, and serine (Fmoc-Asp(...

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Abstract

The invention relates to an osteoblast targeted vector constructed based on a polypeptide. The targeted vector comprises a target head and a support. The target head is the polypeptide. The grafting mass ratio of the target head is 5-10%, and the mole grafting ratio is 2-6%. The targeted vector is prepared by subjecting the polypeptide and a vector to carboxylic acid covalent linking through polyethylene glycol, and is used for filling medicines treating bone fractures, osteoporosis, osteoarthritis, rheumatoid arthritis or tumor bone metastasis. Compared with the prior art, the targeted vector has osteoblast targeting performance, high bone tissue affinity and efficient medicine delivery capability, and is capable of enhancing osteogenesis effects, reducing medicine using amounts, and reducing cell toxicity and side effects. The targeted vector provides an important medicine delivery tool for future osteoporosis treatment.

Description

technical field [0001] The invention relates to the field of biological materials, in particular to a polypeptide-based osteoblast targeting carrier and its preparation and application. Background technique [0002] Bone is a highly specific connective tissue in higher vertebrates, which provides support for the body and muscle attachment sites. It is also a major source of inorganic ions and actively participates in the balance of calcium and phosphorus in the body. The normal development and maintenance of bone requires continuous resorption and remodeling of bone. Under physiological conditions, this balance is coordinated, the functions of osteocytes, osteoclasts, and osteoblasts are normal, and the integrity of bone mass and microstructure remains in a stable state. However, this bone remodeling imbalance is an important cause of numerous bone diseases including osteoporosis, Paget's disease, osteoporosis, bone metastases, rheumatoid arthritis, osteomyelitis, etc. ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/42A61K47/34A61K9/19A61K45/00A61P19/10A61P19/08A61P19/02A61P35/04
CPCA61K9/0019A61K9/19A61K45/00A61K47/34A61K47/42
Inventor 孙瑶
Owner TONGJI UNIV
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