Paclitaxel and lapatinib compound nanocrystal and preparation method thereof

Abstract

The invention belongs to the field of pharmaceutical preparations, and relates to a paclitaxel lapatinib compound nanocrystal and a preparation method thereof. The compound nanocrystal is uniform in particle size, is spherical or nearly spherical, and contains paclitaxel and lapatinib at the same time, the paclitaxel drug loading capacity is 20-40%, the lapatinib drug loading capacity is 10-20%, and the mass ratio of paclitaxel to lapatinib is 1: 1-4: 1. The compound nanocrystal provided by the invention can solve the common problem of the two medicines in construction of injections, and meanwhile, the two medicines can achieve a synergistic effect; the compound nanocrystal has good stability after being coated with the phospholipid surface, is suitable for intravenous administration, canfurther improve the capability of being taken by tumor cells through targeted functional modification, and is suitable for treating various tumors after intravenous administration.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations, and relates to a paclitaxel lapatinib compound nanocrystal and a preparation method thereof. Background technique [0002] The prior art discloses that paclitaxel (Paclitaxel, PTX) is a classic antitumor drug, which mainly causes mitotic arrest and cell apoptosis by stabilizing the microtubule structure in cells, and is widely used in the treatment of various types of entities. tumor. Studies in recent years have shown that when PTX is used in combination with molecularly targeted drugs (small molecule targeted drug lapatinib targeting epidermal growth factor receptor), they can use their different action principles to act on different cell cycle stages or metabolic pathways, and work together In tumor cells, to achieve the purpose of synergistic effect, it has significant advantages in the treatment of breast cancer and other malignant tumors (YardleyD.A.Phase II study evalu...

AI Technical Summary

Problems solved by technology

However, studies have shown that the low water solubility of paclitaxel and lapatinib has created a major problem in formulation; the solubility of paclitaxel in water is only 0.5 μg / mL, and the cosolvent contained in its injection can induce allergic reactions, Large doses of antiallergic drugs must be given in advance for prevention; and the water solubility of lapatinib is also very poor, with a solubility of 0.007mg / mL in water, which leads to difficulties in preparing injection forms. Therefore, the current clinical application has to use oral tablets form with less than 20% oral bioavailability

[0003] Therefore, the researchers intend to pack paclitaxel and lapatinib into the same nanocarrier system, which can not only solve the common problems of the two drugs in the construction of injection dosage forms, but also facilitate the synergy of the two drugs, killing two birds with one stone; however, according to Studies have shown that due to the inherent structural characteristics of micelles, the drug loading of paclitaxel and lapatinib are both lower than 10%, which obviously limits the full exertion of pharmacological effects;

[0004] At present, there are very few reports on paclitaxel / lapatinib co-loaded injection preparations, such as the brain-targeted modification of paclitaxel / lapatinib co-loaded with polyethylene glycol- Polylactic acid (PEG-PLA) micelles, which involve the limitations of the inherent structural characteristics of micelles, the drug loading of paclitaxel and lapatinib are both low, which limits the full play of pharmacological effects and other defects

[0005] In recent years, drug nanocrystals with high drug-loading characteristics have attracted great attention from researchers in the field of pharmaceutical preparations; if paclitaxel and lapatinib are respectively made into nanocrystals, there must be certain differences in the size and surface properties of the particles. Differences, the behavior in the circulation and the distribution to the tumor after injection will also be different, affecting the synergistic effect, so it is necessary to make the two into compound crystals; on the other hand, paclitaxel and lapatinib are both It tends to form needle-shaped crystals, but practice has proved that needle-shaped nano-crystals have poor stability, are difficult to functionalize, and are easy to block blood vessels in the blood circulation. They lack sufficient practicability for intravenous administration. form improvement

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