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CK21 nano preparation and preparation method thereof

A nano-formulation, CK21 technology, applied in the field of medicine, can solve the problems of intolerant and unpredictable clinical use

Inactive Publication Date: 2021-03-09
CINKATE PHARMA INTERMEDIATES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, water-soluble derivatives PG490-88Na, Minnelide, etc. Among them, PG490-88Na has entered Phase I clinical trials as an antineoplastic drug, but there are high inter-individual differences due to toxic side effects and pharmacokinetic properties in the test (2~ 3 times), and the degree of conversion into the active metabolite triptolide was unpredictable and was forced to stop (Kitzen J J, de Jonge M J, Lamers CH, et al.Phase I dose-escalation study of F60008, a novel apoptosis inducer , patients with advanced solid tumors[J].European Journal of Cancer,2009,45(10):1764-1772.)
In addition, Chinese patent CN106946975A discloses a fat-soluble derivative of triptolide (obtained by esterification of triptolide and saturated fatty acid), and nano preparations such as liposomes of the derivative, although the patent provides And triptolide respectively with MA, PA, SA esterification derived derivative liposomes in SD rats in vivo active metabolite triptolide half-life is equivalent to 5.36 times, 6.73 times, 8.28 times of triptolide solution respectively , but there is no mention of the in vivo toxicity of this derivative, and the in vivo toxicity plays a crucial role in clinical use. If the toxicity is still too high, clinical use will be difficult to tolerate

Method used

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  • CK21 nano preparation and preparation method thereof
  • CK21 nano preparation and preparation method thereof
  • CK21 nano preparation and preparation method thereof

Examples

Experimental program
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Effect test

preparation example Construction

[0074] Typically, the preparation method of described fat emulsion comprises the steps:

[0075] Weigh medium-chain triglyceride and stabilizer for injection, mix well, add CK21, stir at 50-120°C to dissolve, cool down to about 70°C after dissolving, and obtain oil phase; refine lecithin, distearoyl Phosphatidylethanolamine-polyethylene glycol, glycerol, dispersed in water at about 70°C to obtain the water phase; inject the oil phase into the water phase, shear and emulsify to obtain colostrum, dilute to the full amount with water for injection; Place in a high-pressure homogenizer, further emulsify under a homogenizing pressure of 10,000 to 20,000 psi, adjust the pH with a pH regulator, subpackage, seal, and sterilize to obtain CK21 fat emulsion injection.

[0076] In another preferred example, the stabilizer is either dissolved in the oil phase or dissolved in the water phase.

[0077] In another preferred example, the sterilization is high-pressure steam sterilization, whe...

Embodiment 1

[0093] The solubility of embodiment 1 CK21 in injection oil

[0094]In the study, it was found that different oil phases and the composition of the oil phase have huge differences in the dissolution of CK21 drugs, so choosing a suitable oil has an important impact on the preparation of CK21 emulsions. Therefore, the corresponding investigation is carried out for the oil phase. Medicinal oil solutions of medium chain triglyceride, ethyl oleate, soybean oil, and mixed oil phase of medium chain triglyceride and soybean oil were prepared respectively, and placed in a refrigerated environment.

[0095] Take a series of CK21 oil solutions refrigerated for 5 days, centrifuge, and take the supernatant for testing. Accurately weigh an appropriate amount of supernatant, dissolve it with absolute ethanol to about 0.1mg / ml, to obtain the test solution; accurately weigh an appropriate amount of CK21, dissolve it with absolute ethanol to about 0.1mg / ml, to obtain a control solution; 20 μl...

Embodiment 2

[0100] The impact of embodiment 2 phospholipid types on the content of CK21 fat emulsion

[0101] Emulsifier is one of the important auxiliary materials for preparing emulsion and maintaining the stability of emulsion. In order to select a suitable emulsifier, a systematic parallel comparative study is carried out on other emulsifiers and lecithin types under the same prescription and dosage, such as Tween 80, Egg yolk lecithin (PL100M), hydrogenated soybean lecithin (HSPC), egg yolk lecithin (PC-98T), egg yolk lecithin (E80), high-purity egg yolk lecithin (EPCS). The comparative prescriptions are shown in Table 2:

[0102] Table 2

[0103] components Prescription 1 Prescription 2 Prescription 3 Prescription 4 Prescription 5 Prescription 6 CK21 5mg 5mg 5mg 5mg 5mg 5mg medium chain triglycerides 2g 2g 2g 2g 2g 2g Tween 80 0.2g / / / / / PL100M / 0.2g / / / / HSPCs / / 0.2g / / / PC-98T / ...

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Abstract

The invention relates to a CK21 nano preparation and a preparation method thereof. Specifically, the invention discloses the CK21 nano preparation which is safe, stable, small in toxic and side effects, obvious in-vivo drug metabolism advantages, long in half-life period and convenient for industrial production, the clinical administration requirements of triptolide derivatives are met, and the preparation has a wide clinical application prospect.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a CK21 nano preparation and a preparation method thereof. Background technique [0002] Triptolide is an epoxy diterpenoid lactone compound isolated from the plant of the traditional Chinese medicine Tripterygium wilfodii Hook F. It has strong pharmacological activities, mainly including anti-inflammatory, immunosuppressive, anti-tumor , anti-fertility, etc. (Liu Q. Triptolide and its expanding multiple pharmacological functions [J]. International Immunopharmacology, 2011, 11(3): 377-383). As an antitumor drug, triptolide has the following characteristics: ① It has broad-spectrum antitumor activity, and has obvious inhibitory effect on primary tumors of breast cancer, bladder cancer, gastric cancer and melanoma, and has the same effect as tumor suppressor gene (P53 ) state; ②has stronger antitumor activity than traditional antitumor drugs, and can produce strong antitumor activ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K9/19A61K31/585A61K47/24A61K47/14A61K47/34A61K47/44A61P35/00
CPCA61K9/0019A61K9/1075A61K9/19A61K31/585A61K47/34A61K47/44A61P35/00
Inventor 张鹏仇波肖飞
Owner CINKATE PHARMA INTERMEDIATES