Orthoester miscible substance pharmaceutic adjuvant, preparation method and local sustained-release drug delivery preparation containing orthoester miscible substance pharmaceutic adjuvant

A technology of pharmaceutical excipients and orthoesters, which is used in pharmaceutical formulations, medical preparations without active ingredients, and medical preparations containing active ingredients, etc. To solve problems such as sexuality, to achieve the effect of simple preparation method, improved therapeutic index and compliance

Pending Publication Date: 2022-04-19
ANHUI UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The technical problem to be solved by the present invention is that the pharmaceutical excipients in the prior art are solid or semi-solid, have no fluidity or poor fluidity, and cannot be directly used as good solvents to dissolve medicines, nor can they be directly used in local injections, creams and Ointment, the repeatability of each batch is poor, and it is easy to destroy the structure of the drug. It provides an orthoester miscible pharmaceutical excipient, a preparation method, and a local sustained-release drug preparation containing the excipient

Method used

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  • Orthoester miscible substance pharmaceutic adjuvant, preparation method and local sustained-release drug delivery preparation containing orthoester miscible substance pharmaceutic adjuvant
  • Orthoester miscible substance pharmaceutic adjuvant, preparation method and local sustained-release drug delivery preparation containing orthoester miscible substance pharmaceutic adjuvant
  • Orthoester miscible substance pharmaceutic adjuvant, preparation method and local sustained-release drug delivery preparation containing orthoester miscible substance pharmaceutic adjuvant

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0074] Synthesis of orthoester compound 4,4'-(oxybis(methylene))bis(2-methoxy-1,3-dioxolane)(OE-1)

[0075] Under nitrogen protection, diglycerol (16.6g, 0.1mol), trimethyl orthoformate (31.84g, 0.3mol) and p-toluenesulfonic acid (344.4mg, 0.002mol) were added to the reaction flask, and acetonitrile (150mL ) was dissolved and reacted overnight at room temperature. After the crude product was distilled off under reduced pressure to remove acetonitrile, ethyl acetate was added to dissolve it, extracted with saturated sodium carbonate solution, dried over anhydrous magnesium sulfate, ethyl acetate and excess trimethyl orthoformate were distilled off under reduced pressure to obtain a colorless oily product, The rate is 83%, 1 H NMR as figure 1 shown.

Embodiment 2

[0077] Synthesis of ortho ester compound 4,4'-(oxybis(methylene))bis(2-methoxy-4-methyl-1,3-dioxolane)(OE-2)

[0078] Under nitrogen protection, diglycerol (16.6g, 0.1mol), trimethyl orthoacetate (36.05g, 0.3mol) and p-toluenesulfonic acid (344.4mg, 0.002mol) were added to the reaction flask, and acetonitrile (150mL ) was dissolved and reacted overnight at room temperature. After the crude product was distilled off under reduced pressure to remove acetonitrile, ethyl acetate was added to dissolve it, extracted with saturated sodium carbonate solution, dried over anhydrous magnesium sulfate, ethyl acetate and excess trimethyl orthoformate were distilled off under reduced pressure to obtain a colorless oily product, The rate is 78%, 1 H NMR as figure 2 shown.

Embodiment 3

[0080] Synthesis of ortho ester compound 4,4'-(oxybis(methylene))bis(4-ethyl-2-methoxy-1,3-dioxolane)(OE-3)

[0081] Under nitrogen protection, diglycerol (16.6g, 0.1mol), trimethyl orthopropionate (40.25g, 0.3mol) and p-toluenesulfonic acid (344.4mg, 0.002mol) were added to the reaction flask, and dichloro Methane (150 mL) was dissolved and reacted overnight at room temperature. After the crude product was distilled off under reduced pressure to remove acetonitrile, ethyl acetate was added to dissolve it, extracted with saturated sodium carbonate solution, dried over anhydrous magnesium sulfate, ethyl acetate and excess trimethyl orthoformate were distilled off under reduced pressure to obtain a colorless oily product, The rate is 81%, 1 H NMR as image 3 shown.

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Abstract

The invention discloses an orthoester miscible pharmaceutical adjuvant, which relates to the field of pharmaceutical adjuvants and is mainly obtained by mixing and dissolving different orthoester compounds according to different proportions or mixing and dissolving orthoester compounds and biocompatible medical polymer materials according to different proportions. The chemical formula I of the orthoester compound is shown in the specification, wherein R represents hydrogen, methyl, ethyl, propyl, isopropyl, butyl or phenyl. The invention also provides a preparation method of the pharmaceutic adjuvant and a local sustained-release drug delivery preparation containing the adjuvant. The invention has the following beneficial effects: the fluidity of the orthoester miscible pharmaceutical adjuvant is adjustable; the degradation rate is adjustable, and the drug release rate is adjustable; a good solvent, which can dissolve small molecule and protein drugs; local injections, cream and ointment can be prepared; the biological compatibility is good, the metabolism is clear, and the clinical conversion use is easy.

Description

technical field [0001] The invention relates to the field of pharmaceutical excipients, in particular to an orthoester miscible pharmaceutical excipient, a preparation method, and a local sustained-release drug preparation containing the excipient. Background technique [0002] Poly(ortho esters), POE is an acid-sensitive biodegradable polymer material. Since it was first synthesized by Jorge Heller and his colleagues in the United States in the 1960s, it has been clinically used because of its unique properties. has been extensively researched and applied. The orthoester bond has a self-catalytic function, which can endow drug excipients with specific physiological and microenvironmental responsiveness as required, and achieve long-term sustained release and targeted enrichment of drugs at the site of action through dynamic changes in physical and chemical properties, thereby enhancing the therapeutic effect. Therefore, the construction of human body-specific pH (ultra)sen...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/06A61K45/00A61K47/10A61K47/22A61K47/34C07D317/34
CPCA61K47/22A61K47/34A61K47/10A61K45/00A61K9/06A61K9/0019C07D317/34
Inventor 唐汝培闫国卿
Owner ANHUI UNIVERSITY
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