Doxorubicin hydrochloride light-controlled sustained-release liquid crystal gel preparation and preparation method thereof

Abstract

The invention discloses a doxorubicin hydrochloride light-controlled sustained-release liquid crystal gel preparation and a preparation method thereof. The light-controlled sustained-release liquid crystal gel preparation is prepared from 15-40 wt% of phospholipid, 60-70 wt% of glyceride, 1-20 wt% of a cosolvent, 0.01-2 wt% of doxorubicin hydrochloride and 0.001-0.2 wt% of a photosensitizer. The doxorubicin hydrochloride light-controlled sustained-release liquid crystal gel preparation has the advantages of low viscosity, good fluidity, easiness in injection, rapidness in formation of the liquid crystal gel after being injected into or around a tumor or being placed in a post-operative tumor cavity, and realization of in-situ slow release of doxorubicin hydrochloride; and lights cause phase change of the liquid crystal gel and increase the drug release rate, and the preparation prolongs the drug action time, reduces the administration frequency, reduces the toxic and side effects of the drug, releases the drug as needed by adjusting the release of the drug through adjusting the illumination frequency or time according to the tumor pathological conditions of a patient, and greatly improves the bioavailability of the drug.

Description

technical field

[0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a doxorubicin hydrochloride light-controlled sustained-release liquid crystal gel preparation and a preparation method thereof. Background technique

[0002] Lyotropic liquid crystals are mainly an ordered system formed by one or more amphiphilic compounds and solvents. There are lattices inside. The orderly arrangement of lattices and the strong interaction between amphiphiles make them It is gel-like in appearance. Lyotropic liquid crystals have attracted the attention of many scientists due to their own structural characteristics, and are gradually used as carriers of various drugs, which can achieve long-term sustained release of various polar drugs in the body.

[0003] Doxorubicin is an anthracycline antitumor antibiotic, which can inhibit the synthesis of RNA and DNA, thereby preventing the growth of tumor cells. It has a wide antitumor spectrum and ...

Examples

Embodiment 1

[0037] A light-controlled sustained-release liquid crystal gel preparation of doxorubicin hydrochloride, which is prepared from the following raw materials in percentage by weight: 25.99% phosphatidylcholine, 60% glyceryl dioleate, 13.88% absolute ethanol, and doxorubicin hydrochloride 0.1%, IR8200.03%.

[0038] The preparation method of the doxorubicin hydrochloride light-controlled slow-release liquid crystal gel preparation is as follows: after mixing phosphatidylcholine, diolein glyceride, doxorubicin hydrochloride and IR820 according to the weight percentage, then add the The absolute ethanol in the weight percentage is mixed evenly on a mixer to make it completely dissolved, and the doxorubicin hydrochloride light-controlled sustained-release liquid crystal gel preparation is obtained, which is sealed and stored at 4°C.

[0039] The appearance of the product obtained in this example is a light yellow transparent solution, which shows that each raw material has good compa...

Embodiment 2

[0042] A doxorubicin hydrochloride light-controlled slow-release liquid crystal gel preparation, prepared from the following raw materials in weight percentage: 35% phosphatidylcholine, 52% glyceryl dioleate, 12.12% absolute ethanol, doxorubicin hydrochloride 0.8%, IR8200.08%.

[0043] The preparation method is the same as in Example 1.

[0044] The appearance of the product obtained in this example is a light yellow transparent solution, which shows that each raw material has good compatibility and is evenly mixed. There is no delamination phenomenon after storage at -4°C for 6 months and centrifugation treatment, indicating that the product has good storage stability.

[0045] In this example, the cumulative release rate of doxorubicin hydrochloride in the light-controlled sustained-release liquid crystal gel preparation precursor of doxorubicin hydrochloride within one week without and with light were 10.05±0.43% and 22.25±0.21%, respectively. The results are as follows ...

Embodiment 3

[0047] A light-controlled sustained-release liquid crystal gel preparation of doxorubicin hydrochloride, which is prepared from the following raw materials in percentage by weight: phosphatidylcholine 25%, glyceryl dioleate 54.45%, absolute ethanol 20%, doxorubicin hydrochloride 0.5%, IR8200.05%.

[0048] The preparation method is the same as in Example 1.

[0049] The appearance of the product obtained in this example is a light yellow transparent solution, which shows that each raw material has good compatibility and is evenly mixed. There is no delamination phenomenon after storage at -4°C for 6 months and centrifugation treatment, indicating that the product has good storage stability.

[0050] In this embodiment, the cumulative release rate of doxorubicin hydrochloride in the precursor of doxorubicin hydrochloride light-controlled slow-release liquid crystal gel preparation is about 21.15±0.18% within a week without and with light, and the results are as follows image ...

technical field

[0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a doxorubicin hydrochloride light-controlled sustained-release liquid crystal gel preparation and a preparation method thereof. Background technique

[0002] Lyotropic liquid crystals are mainly an ordered system formed by one or more amphiphilic compounds and solvents. There are lattices inside. The orderly arrangement of lattices and the strong interaction between amphiphiles make them It is gel-like in appearance. Lyotropic liquid crystals have attracted the attention of many scientists due to their own structural characteristics, and are gradually used as carriers of various drugs, which can achieve long-term sustained release of various polar drugs in the body.

[0003] Doxorubicin is an anthracycline antitumor antibiotic, which can inhibit the synthesis of RNA and DNA, thereby preventing the growth of tumor cells. It has a wide antitumor spectrum and ...

Examples

Embodiment 1

[0037] A light-controlled sustained-release liquid crystal gel preparation of doxorubicin hydrochloride, which is prepared from the following raw materials in percentage by weight: 25.99% phosphatidylcholine, 60% glyceryl dioleate, 13.88% absolute ethanol, and doxorubicin hydrochloride 0.1%, IR8200.03%.

[0038] The preparation method of the doxorubicin hydrochloride light-controlled slow-release liquid crystal gel preparation is as follows: after mixing phosphatidylcholine, diolein glyceride, doxorubicin hydrochloride and IR820 according to the weight percentage, then add the The absolute ethanol in the weight percentage is mixed evenly on a mixer to make it completely dissolved, and the doxorubicin hydrochloride light-controlled sustained-release liquid crystal gel preparation is obtained, which is sealed and stored at 4°C.

[0039] The appearance of the product obtained in this example is a light yellow transparent solution, which shows that each raw material has good compa...

Embodiment 2

[0042] A doxorubicin hydrochloride light-controlled slow-release liquid crystal gel preparation, prepared from the following raw materials in weight percentage: 35% phosphatidylcholine, 52% glyceryl dioleate, 12.12% absolute ethanol, doxorubicin hydrochloride 0.8%, IR8200.08%.

[0043] The preparation method is the same as in Example 1.

[0044] The appearance of the product obtained in this example is a light yellow transparent solution, which shows that each raw material has good compatibility and is evenly mixed. There is no delamination phenomenon after storage at -4°C for 6 months and centrifugation treatment, indicating that the product has good storage stability.

[0045] In this example, the cumulative release rate of doxorubicin hydrochloride in the light-controlled sustained-release liquid crystal gel preparation precursor of doxorubicin hydrochloride within one week without and with light were 10.05±0.43% and 22.25±0.21%, respectively. The results are as follows ...

Embodiment 3

[0047] A light-controlled sustained-release liquid crystal gel preparation of doxorubicin hydrochloride, which is prepared from the following raw materials in percentage by weight: phosphatidylcholine 25%, glyceryl dioleate 54.45%, absolute ethanol 20%, doxorubicin hydrochloride 0.5%, IR8200.05%.

[0048] The preparation method is the same as in Example 1.

[0049] The appearance of the product obtained in this example is a light yellow transparent solution, which shows that each raw material has good compatibility and is evenly mixed. There is no delamination phenomenon after storage at -4°C for 6 months and centrifugation treatment, indicating that the product has good storage stability.

[0050] In this embodiment, the cumulative release rate of doxorubicin hydrochloride in the precursor of doxorubicin hydrochloride light-controlled slow-release liquid crystal gel preparation is about 21.15±0.18% within a week without and with light, and the results are as follows image ...

Images