# US 10,307,373 B2 · Drug delivery formulation for controlling of initial burst and manufacturing method thereof

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- Number: US 10,307,373 B2
- Document ID: US10307373B2
- Status: Granted
- Kind: B2
- Application number: 13/022,734
- Filed: 2011-02-08
- Published: 2012-07-12
- Granted: 2019-06-04
- Earliest claimed: 2011-01-12
- Assignees: Ajou University Industry-Academic Cooperation Foundation
- Applicants: Moon Suk Kim; Da Yeon Kim
- Inventors: Moon Suk Kim; Da Yeon Kim
- Web page: https://patentgrep.com/patent/US10307373B2

## CPC

- A61K 9/10: Dispersions; Emulsions
- A61K 9/0024: {Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L)}
- A61K 9/1647: {Polyesters, e.g. poly(lactide-co-glycolide)}
- A61K 9/1694: {resulting in granules or microspheres of the matrix type containing more than 5% of excipient}
- A61K 9/5031: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)}
- A61K 9/5089: {Processes}
- A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Provided is a drug delivery system for control of initial burst of a drug. More particularly, there are provided a drug delivery formulation including: a granule containing a biodegradable polymer and a drug; and a temperature-sensitive hydrogel, and a method for preparing the same. The presently disclosed drug delivery formulation can be prepared via a relatively simple process and allows a drug to be released slowly at a constant rate without initial burst and thus maintains a constant blood level of the drug for a long period of time. Consequently, it is capable of preventing the initial burst of the existing injection-type drug delivery formulations and slow-release granules and providing a desired release profile, including sustained release with time.

## Claims

### Claim 1

A drug delivery formulation comprising a plurality of granules suspended in a temperature-sensitive hydrogel, each granule comprising a biodegradable polymer forming the shell of the granule and a protein or peptide drug forming the core of the granule
wherein the temperature-sensitive hydrogel is carboxymethyl cellulose(CMC)/polyethyleneimine(PEI) hydrogel,
wherein the biodegradable polymer is poly(lactide-co-glycolide)(PLGA), and
wherein the drug release is controlled by the shell of the granule and then by the temperature-sensitive hydrogel, reducing the initial burst of the drug and obtaining a sustained release of the drug.

### Claim 2 (depends on 1)

A method for preparing the drug delivery formulation according to claim 1, comprising:
incorporating a protein or peptide drug into a biodegradable polymer having a molecular weight 10,000-200,000 g/mol to prepare a granule wherein the drug is entrapped; and
mixing a plurality of the prepared granules with a temperature-sensitive hydrogel to suspend the plurality of granules in the temperature-sensitive hydrogel to form a drug delivery formulation,
wherein the biodegradable polymer is PLGA, and the temperature-sensitive hydrogel is carboxymethyl cellulose(CMC)/polyethyleneimine(PEI) hydrogel.

### Claim 3 (depends on 1)

The method for preparing the drug delivery formulation according to claim 1, wherein the incorporation is performed by ultrasonic spraying or using a syringe.