EP-4736879-A1 - SUSTAINED-RELEASE ANALGESIC PHARMACEUTICAL COMPOSITION, METHOD FOR PREPARING SAME, AND USE THEREOF

EP4736879A1EP 4736879 A1EP4736879 A1EP 4736879A1EP-4736879-A1

Abstract

The present application belongs to the field of pharmaceutical preparations, and particularly relates to a sustained-release analgesic pharmaceutical composition, a method for preparing same, and use thereof. The pharmaceutical composition of the present application comprises a drug, a delivery carrier, and a release regulator. The drug is selected from at least one of a local anesthetic and a non-steroidal anti-inflammatory drug. The release regulator is selected from a phospholipid compound. The delivery carrier is selected from a saccharide and an esterified form thereof. According to the present application, the coaction of the phospholipid compound and the delivery carrier can increase the plasma drug concentration upon the initial release in vivo, reduce the time to peak, enhance the analgesic effect in the early stage after a surgery, and ensure the long-term release of the drug, thus effectively relieving the postoperative pain, reducing the administration frequency, and promoting skin wound healing. The use of a specific solubilizer provides good stability for the drug and prevents precipitation. The composition can be administered through the wound, making it easy to use.

Inventors

LI, Fengquan
YE, Qiongru
LI, Jianxuan

Assignees

Brightintel Biotech Pharmaceutical Co., Ltd.

Dates

Publication Date: 20260506
Application Date: 20241220

Claims (13)

A pharmaceutical composition, characterized by comprising a drug, a delivery carrier, and a release-regulating agent; wherein the drug is at least one selected from the group consisting of a local anesthetic and a nonsteroidal anti-inflammatory drug; wherein the release-regulating agent is selected from a phospholipid compound; and wherein the delivery carrier is selected from the group consisting of a saccharide and an esterified form thereof.
The pharmaceutical composition according to claim 1, characterized in that when the drug contains the local anesthetic, the pharmaceutical composition further contains a solubilizer; preferably, the solubilizer is at least one selected from the group consisting of menthol, camphor, borneol, linalool, and eucalyptol.
The pharmaceutical composition according to claim 1, characterized in that the local anesthetic is selected from an amide anesthetic; preferably, the amide anesthetic is at least one selected from the group consisting of bupivacaine, ropivacaine, and a pharmaceutically acceptable salt or a stereoisomer thereof; the nonsteroidal anti-inflammatory drug is at least one selected from the group consisting of meloxicam, celecoxib, and a pharmaceutically acceptable salt or a stereoisomer thereof.
The pharmaceutical composition according to claim 1, characterized in that the delivery carrier is at least one selected from the group consisting of sucrose, chitosan, sucrose acetate isobutyrate, sucrose octaacetate, and sucrose monoacetate monoisobutyrate.
The pharmaceutical composition according to claim 1, characterized in that the phospholipid compound is at least one selected from the group consisting of a natural phospholipid and a synthetic phospholipid; preferably, the natural phospholipid is at least one selected from the group consisting of a soybean phosphatidylcholine, an egg yolk phosphatidylcholine, a rapeseed phospholipid, and a sunflower phospholipid; and the synthetic phospholipid is at least one selected from the group consisting of dierucoyl phosphatidylcholine, dioleoyl phosphatidylcholine, palmitoyl oleoyl phosphatidylcholine, distearoyl phosphatidylcholine, dipalmitoyl phosphatidylglycerol, and distearoyl phosphatidylglycerol.
The pharmaceutical composition according to any one of claims 1 to 5, characterized in that after administration of the pharmaceutical composition to an animal, when the drug contains the local anesthetic, the time to peak plasma concentration of the local anesthetic is 0.1 h to 8 h; when the drug is selected from a nonsteroidal anti-inflammatory drug, the time to peak plasma concentration is 1 h to 28 h.
The pharmaceutical composition according to claim 1, characterized in that the pharmaceutical composition comprises 0.01-20 parts by weight of the drug, 30-80 parts by weight of the delivery carrier, and 0.05-20 parts by weight of the release-regulating agent.
The pharmaceutical composition according to claim 2, characterized in that when the drug contains the local anesthetic, the pharmaceutical composition comprises 0.01-20 parts by weight of the drug, 30-80 parts by weight of the delivery carrier, more than 0 and less than or equal to 10 parts by weight of the solubilizer, and 0.05-20 parts by weight of the release-regulating agent.
The pharmaceutical composition according to any one of claims 1 to 5, characterized in that the pharmaceutical composition further comprises a solvent; or, the pharmaceutical composition further comprises a solvent and an antioxidant.
The pharmaceutical composition according to claim 9, characterized in that the pharmaceutical composition comprises 0.01-20 parts by weight of the drug, 30-80 parts by weight of the delivery carrier, 0.05-20 parts by weight of the release-regulating agent, more than 0 and less than or equal to 70 parts by weight of the solvent, and 0-5 parts by weight of the antioxidant.
The pharmaceutical composition according to claim 10, characterized in that when the drug contains the local anesthetic, the pharmaceutical composition comprises 0.01-20 parts by weight of the drug, 30-80 parts by weight of the delivery carrier, more than 0 and less than or equal to 10 parts by weight of the solubilizer, 0.05-20 parts by weight of the release-regulating agent, more than 0 and less than or equal to 70 parts by weight of the solvent, and 0-5 parts by weight of the antioxidant; when the drug is selected from the nonsteroidal anti-inflammatory drug, the pharmaceutical composition comprises 0.1-20 parts by weight of the drug, 30-80 parts by weight of the delivery carrier, 0-10 parts by weight of the solubilizer, 0.05-20 parts by weight of the release-regulating agent, more than 0 and less than or equal to 70 parts by weight of the solvent, and 0-5 parts by weight of the antioxidant.
A method for preparing the pharmaceutical composition of any one of claims 1 to 11, characterized by comprising the step of: mixing raw material components to obtain the pharmaceutical composition.
A pharmaceutical preparation, characterized by comprising the pharmaceutical composition of any one of claims 1 to 11.

Description

TECHNICAL FIELD The present disclosure belongs to the technical field of pharmaceutical preparations, and in particular relates to a sustained-release analgesic pharmaceutical composition, a method for preparing the same and use thereof. BACKGROUND Pain is one of the most common postoperative complications. Currently, one or more drugs among opioid analgesics, non-steroidal anti-inflammatory drugs, and local anesthetics are mainly used for postoperative analgesia in clinical practice. Among them, local anesthetics such as Bupivacaine Hydrochloride Injection and Ropivacaine Hydrochloride Injection have a short duration of action; the analgesic effect of a single dose lasts only 6-8 hours, which cannot meet the treatment cycle of postoperative pain and is difficult to relieve the pain of patients during postoperative treatment for a long time. Meanwhile, there is no sustained-release and long-acting dosage form of anti-inflammatory drugs yet. For example, Anjeso Injection (US11253478B2) is a daily dosage form, which is difficult to meet the requirement of long-term sustained release of drug efficacy for multiple days. Therefore, opioid drugs commonly used clinically or those administered continuously with analgesic pumps not only have poor clinical compliance but also cause many side effects, affecting patients' prognosis. To solve the above problems, the foreign marketed drug Posimir (Publication No.: CN101035562A) uses sucrose acetate isobutyrate as a sustained-release carrier and benzyl alcohol as a solvent, with a bupivacaine concentration of 132 mg/mL and a benzyl alcohol dosage of approximately 22% w/w. Due to the certain neurotoxicity of benzyl alcohol, there may be safety issues when the dosage is large; at the same time, the drug has insufficient efficacy and many adverse reactions at the wound site. The foreign marketed drug Zynrelef (Publication No.: CN115025099A) is a compound preparation of bupivacaine and meloxicam, using polyorthoester polymer as the sustained-release carrier. After being administered to the administration site, it achieves a sustained-release effect through the slow degradation of the polyorthoester itself. During the prescription development, precipitation of bupivacaine is observed, and subsequently, maleic acid is added to the prescription to prevent precipitation of raw materials. However, maleic acid is acidic, which can cause adverse reactions at the wound and affect wound healing. Meanwhile, its drug release rate is slow and the time to peak concentration is long, so it cannot exert the required analgesic effect when patients experience severe pain in the early postoperative period. Therefore, there is an urgent need to provide a sustained-release analgesic pharmaceutical composition that can increase the initial release concentration of the drug in the body, enhance the early analgesic effect, maintain sustained release, and promote good wound healing. SUMMARY The present disclosure aims to solve one or more technical problems existing in the existing technologies, and at least provide a beneficial option or create conditions. Specifically, the present disclosure provides a sustained-release analgesic pharmaceutical composition that can increase the initial release concentration of the drug in vivo, enhance the early analgesic efficacy while maintaining sustained release, and promote good wound healing. The inventive concept of the present disclosure is as follows: the sustained-release analgesic pharmaceutical composition of the present disclosure includes a drug, a delivery carrier, and a release-regulating agent; the drug is at least one selected from the group consisting of a local anesthetic and a nonsteroidal anti-inflammatory drug; the release-regulating agent is selected from a phospholipid compound; the delivery carrier is selected from a saccharide and an esterified form thereof. The present disclosure uses a phospholipid compound as the release-regulating agent, which, together with the delivery carrier, can increase the in vivo plasma concentration upon the initial release, enhance the early analgesic efficacy and maintain sustained release. It is exactly opposite to the existing technologies that delays the sustained release duration of the active pharmaceutical ingredient and has a longer time to reach peak drug release. Furthermore, the pharmaceutical composition of the present disclosure can promote wound healing. Therefore, in a first aspect, the present disclosure provides a sustained-release analgesic pharmaceutical composition. Specifically, the sustained-release analgesic pharmaceutical composition includes a drug, a delivery carrier, and a release-regulating agent; wherein the drug is at least one selected from the group consisting of a local anesthetic and a nonsteroidal anti-inflammatory drug;wherein the release-regulating agent is selected from a phospholipid compound; andwherein the delivery carrier is selected from a saccharide and an esterif