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An osteoblast targeted vector constructed based on a polypeptide and preparation and applications thereof

An osteoblast-targeted technology, applied in medical preparations with non-active ingredients, medical preparations containing active ingredients, bone diseases, etc., can solve the problems of inability to eliminate biological effects, potential toxicity and carcinogenicity, and half-life Short and other problems, to achieve the effects of clear biomineralization ability, low production cost, strong plasticity and low toxicity

Inactive Publication Date: 2016-10-26
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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  • An osteoblast targeted vector constructed based on a polypeptide and preparation and applications thereof
  • An osteoblast targeted vector constructed based on a polypeptide and preparation and applications thereof
  • An osteoblast targeted vector constructed based on a polypeptide and preparation and applications thereof

Examples

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Embodiment 1

[0046] An osteoblast targeting carrier constructed based on a polypeptide, the targeting carrier comprises a target head and a scaffold, the target head and the scaffold The target head and the scaffold are covalently connected by polydiethanol carboxylic acid (PEG-COOH). The mass branch rate of the target head is about 6%, and the molar branch 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, where Ser represents serine and Asp represents aspartic acid; the scaffold is a polyurethane scaffold.

[0047] The above-mentioned targeting vector, its synthesis method such as figure 1 As shown, including the following steps:

[0048] (1) Preparation of the target head: A twelve-channel semi-automatic peptide synthesizer was used to synthesize the target head using the amino acid condensation sequence connection method. Serine (Fmoc-Asp(otBu)-OH) and aspartic acid (Fmoc-Ser(Tb...

Embodiment 2

[0059] An osteoblast targeting carrier constructed based on a polypeptide, the targeting carrier comprises a target head and a scaffold, and the target head and the scaffold are covalently connected through polydiethanol carboxylic acid (PEG-COOH). The mass branch 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, where Ser represents serine and Asp represents aspartic acid; the scaffold is a polyurethane scaffold.

[0060] The synthesis method of the above-mentioned targeting vector includes the following steps:

[0061] (1) Preparation of the target head: A twelve-channel semi-automatic peptide synthesizer was used to synthesize the target head using the amino acid condensation sequence connection method. Serine (Fmoc-Asp(otBu)-OH) and aspartic acid (Fmoc-Ser(Tbu) )-OH) Connect in the order of Ser-Asp to obtain Ser Asp of the target head, ready for use;

[0062] (2) Prepar...

Embodiment 3

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

[0068] The synthetic method of the above targeting vector includes the following steps:

[0069] (1) Preparation of the target head: A twelve-channel semi-automatic peptide synthesizer was used to synthesize the target head using the amino acid condensation sequence connection method. Serine (Fmoc-Asp(otBu)-OH) and aspartic acid (Fmoc-Ser(Tbu) )-OH) Connect...

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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 present 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 the main source of inorganic ions and actively participates in the balance of calcium and phosphorus in the body. The normal development and maintenance of bones requires continuous bone resorption and reconstruction. Under physiological conditions, this balance is coordinated. The functions of bone cells, osteoclasts and osteoblasts are normal, and the integrity of bone mass and microstructure is maintained in a stable state. However, this imbalance of bone remodeling is an important cause of many bone diseases including osteoporosis, Paget's disease, osteoporosis, bone metastases, rheumatoid arthritis, osteomyelitis...

Claims

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Application Information

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Patent Type & Authority Applications(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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