Opioid receptor partial agonist supported sustained release microsphere as well as preparation method and application thereof

A technology of opioid receptors and slow-release microspheres, which is applied to medical preparations with non-active ingredients, medical preparations containing active ingredients, and pharmaceutical formulas, etc., which can solve the problems of side effects, research and drug effect interference, and bioavailability In order to avoid problems such as poor accuracy, it can achieve the effect of facilitating industrial scale-up production, ensuring repeatability, and improving drug loading rate

Active Publication Date: 2018-10-26
INST OF PROCESS ENG CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In summary, the current clinical application of opioid receptor partial agonists mainly has problems such as short half-life, low solubility, poor bioavailability, and easy side effects, which make it difficult to meet the needs of indication treatment. Slow-release microspheres, there are technical obstacles, including:
[0007] Due to the limitation of preparation technology (stirring, spraying, etc.), the particle size of the obtained opioid receptor partial agonist microspheres is not uniform, resulting in poor repeatability between different batches, which interferes with subsequent research and drug efficacy, release behavior and cycle. It is difficult to summarize the rules and precise control;
[0008] Opioid receptor partial agonists have low solubility in water and oil-phase organic solvents of the traditional single-emulsion method, resulting in the inability to be prepared by the conventional single-emulsion method and double-emulsion method, and the technical difficulties are relatively large
[0009] The existence of the above-mentioned technical barriers has led to little research on the sustained-release microspheres of opioid receptor partial agonists, and the pharmaceutical market urgently needs to develop sustained-release microspheres loaded with opioid receptor partial agonists for long-term sustained release.

Method used

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  • Opioid receptor partial agonist supported sustained release microsphere as well as preparation method and application thereof
  • Opioid receptor partial agonist supported sustained release microsphere as well as preparation method and application thereof
  • Opioid receptor partial agonist supported sustained release microsphere as well as preparation method and application thereof

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preparation example Construction

[0054] The invention also discloses a preparation method of slow-release microspheres loaded with an opioid receptor partial agonist, comprising the following steps:

[0055] Step A, dissolving the opioid receptor partial agonist (drug) in a first organic solvent to form an internal oil phase (O1);

[0056] Step B, dissolving the degradable polymer material in at least one second organic solvent to form an external oil phase (O2);

[0057] Step C, preparing by injecting the inner oil phase (O1) obtained in step A into the outer oil phase (O2) obtained in step B and uniformly mixing to form an O1 / O2 mixed dispersed phase;

[0058] Step D, adding the mixed oil phase obtained in step C to the external water phase (W) containing a stabilizer to form an O1 / O2 / W pre-emulsion;

[0059] Step E, passing the pre-emulsion obtained in step D through a microporous membrane under pressure to form a uniform O1 / O2 / W emulsion;

[0060] In step F, the homogeneous emulsion obtained in step E i...

Embodiment 1

[0091] A hydrophilic and uniform porous membrane with a pore diameter of 35 μm is soaked in water to fully wet the porous membrane. Dissolve 100 mg of dezocine at a concentration of 25 mg / mL in 4 mL of ethanol as the internal oil phase (O1), and simultaneously add 1 g of polylactic acid-polyhydroxyl Acetic acid copolymer (PLGA) was dissolved in 10 mL of dichloromethane as the external oil phase (O2). Dissolve 1 g of polyvinyl alcohol (PVA) in 100 mL of distilled water and stir evenly as the external water phase. Add the inner oil phase to the outer oil phase and homogenize at 6000rpm, mix for 30s to obtain a uniformly mixed O1 / O2 mixed oil phase, then add the mixed oil phase to the outer water phase and continue to homogeneously emulsify for 3 minutes to obtain a pre-emulsion O1 / O2 / W, the pre-emulsion O1 / O2 / W is pressed through the microporous membrane device under the operating pressure of 300kPa (operating steps such as figure 1 shown), the emulsion was obtained, and the ...

Embodiment 2

[0093] A hydrophilic porous membrane with a uniform pore diameter of 30 μm is soaked in water to fully wet the porous membrane. 200 mg of pentazocine with a concentration of 50 mg / mL was dissolved in 4 mL of glycerol as the internal oil phase (O1), and 2 g of polylactic acid with a molecular weight of 10,000 (polylactic acid:polyglycolic acid=50:50) - Polyglycolic acid copolymer (PLGA) was dissolved in 10 mL of dichloromethane as the external oil phase (O2). Dissolve 1 g of polyvinyl alcohol (PVA) in 100 mL of distilled water and stir evenly as the external water phase (W). Add the inner oil phase to the outer oil phase and homogenize at 9000rpm, mix for 60s to obtain a mixed oil phase O1 / O2, then add the mixed oil phase to the outer water phase and continue to homogeneously emulsify for 5 minutes to obtain a pre-emulsion O1 / O2 / W. The pre-emulsion O1 / O2 / W was pressed through the microporous membrane device at an operating pressure of 600kPa to obtain an emulsion. The emulsion...

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Abstract

The invention discloses an opioid receptor partial agonist supported sustained release microsphere as well as a preparation method and application thereof. The opioid receptor partial agonist supported sustained release microsphere has a drug embedding rate of higher than 80%, the initial burst release of the drug is lower than 20% within half an hour, and the drug can realize sustained release ata constant speed for 1-15 days. The preparation method disclosed by the invention is simple in process, the prepared product is uniform in particle size, the repeatability of each batch of products is excellent, industrial production is easily realized, the repeatability of the product is ensured, the curative effect of the drug is stable, the prepared microsphere has excellent re-suspending property in water, and industrial production cost is saved.

Description

technical field [0001] The invention relates to the preparation of sustained-release microspheres in the field of medicine, in particular to a sustained-release microsphere loaded with an opioid receptor partial agonist, its preparation method and application. Background technique [0002] "Pain" is clinically divided into acute pain and chronic pain. Acute pain has a clear etiology and is an acute symptom caused by disease or tissue damage. Clinically, it is common in surgical trauma, acute inflammation, myocardial infarction, visceral perforation, labor pain, etc.; However, the etiology of most chronic pain is not clear, and the mechanism is complex, mostly involving dorsal root ganglion neurons. Patients with chronic pain have complex mental, emotional, and psychological changes, often manifested as inhibition symptoms, mental depression, and avoidance behaviors. Prolonged illness may lead to pessimism, disappointment, and even world-weariness. In recent years, as expert...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K9/50A61K9/52A61K47/34A61K31/439A61K31/135A61P25/04
CPCA61K9/5031A61K31/135A61K31/439A61K45/00A61P25/04
Inventor 马光辉李勋韦祎周炜清苏志国
Owner INST OF PROCESS ENG CHINESE ACAD OF SCI
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