Hydroxypropyl-beta-cyclodextrin; Hydroxypropyl betacyclodextrin is a hydroxylated derivative of β-cyclodextrin. It is one of the betacyclodextrin derivatives that has been studied thoroughly in recent years on preparation methods, toxicological tests and application scope. Hydroxypropyl betacyclodextrin not only has excellent envelope effect on many compounds like betacyclodextrin, but also has high water solubility and improves the release rate and bioavailability of the encapsulated drugs in vivo. Therefore, hydroxypropyl betacyclodextrin has some special excellent properties, and has a wider application range and the most promising application in medicine.
Hydroxypropyl betacyclodextrin is a derivative of betacyclodextrin where the C2, C3, and C8 hydroxyl groups are replaced by hydroxypropyl groups. Due to different reaction conditions, the positions of hydroxypropyl are different, so several systems such as 2-hydroxypropyl betacyclodextrin and 2.3.6-hydroxypropyl betacyclodextrin can be formed.
After the hydroxyl group in betacyclodextrin is replaced by propyl, the hydroxypropyl betacyclodextrin generated is the same as betacyclodextrin in addition to the molecular non-reducibility, stability in alkaline media, decomposition by strong acids, molecular enveloping effect and non-toxic to humans, etc., it also has the following characteristics different from betacyclodextrin. For example:
1, hydroxypropyl betacyclodextrin at room temperature, water solubility is very high, generally more than 50%, so it can not be crystallized in alcohol aqueous solution.
2. The selectivity of hydroxypropyl betacyclodextrin and betacyclodextrin to the enveloped substances is different, and the molecular proportion of the enveloped substances may be changed.
3, hydroxypropyl betacyclodextrin is basically not catabolic in the human body, nor accumulation, oral hydroxypropyl betacyclodextrin most of the excretion with stool, parenteral administration, basically all excreted with urine.
4, hydroxypropyl betacyclodextrin in the biological body can promote the rapid release of enveloped substances.
5, hydroxypropyl betacyclodextrin than betacyclodextrin or other derivatives (such as methylation-betacyclodextrin) has low surface activity, low hemolysis activity, and is safer to use.
Because of the above properties of hydroxypropyl betacyclodextrin, it has received more and more attention in the pharmaceutical field. In order to enhance people's understanding of the application of hydroxypropyl betacyclodextrin, the following examples are illustrated:
1. In terms of increasing the water solubility of insoluble drugs. For example, dihydroartemisinin and artemether are insoluble in water, and their solubility can meet the requirements of powder injection after enveloping with 1 hydroxypropyl betacyclodextrin. The solubility of dioxin in 50% hydroxypropyl betacyclodextrin solution increased from 0.07mg/ml to 68mg/ml in water.
2. In terms of increasing drug stability. For example, after estradiol is enveloped with hydroxypropyl betacyclodextrin and placed at room temperature, its degradation half-life can be extended from 1.2 years to 4 years.
3, in reducing the side effects of drugs. For example, the vasodilator nimodipine is insoluble in water and is susceptible to the first pass of the liver when taken orally. The use of hydroxypropyl betacyclodextrin as an injection for muscular administration can significantly increase the biological absorption of the drug and reduce the damage to gastrointestinal or muscle tissue.
4. In terms of improving drug availability; For example: steroid hormone is hydroxypropyl betacyclodextrin envelope, not only the solubility is high, the release rate is fast, and compared with the unenveloped hormone, the drug level in the blood can be about 2 times higher.
5. In terms of the safety of hydroxypropyl betacyclodextrin. According to systematic subacute and chronic toxicity studies, hydroxypropyl betacyclodextrin does not cause disease or lead to death in mice. After intravenous injection to rabbits, hydroxypropyl betacyclodextrin was rapidly eliminated from the blood and excreted with urine, and there were no adverse symptoms after continuous injection. Intravenous administration of 200mg/kg hydroxypropyl betacyclodextrin did not show clinical effects in mice and monkeys. Oral or intravenous doses of hydroxypropyl betacyclodextrin alone were as high as 15g/kg or 10g/kg, respectively, and did not kill monkeys. Human clinical studies have shown that hydroxypropyl betadextrin is administered orally, intravenously, intravenously, nasal, sublingual, and ocular, with no adverse effects or irritation to the skin, eyes, or muscles. This shows that hydroxypropyl betacyclodextrin is very safe for organisms.
Hydroxypropyl betacyclodextrin is absolutely safe if administered according to the table below.
Administration route and dose of hydroxypropyl betacyclodextrin to human body 1. Total amount of intravenous infusion: 30g. Method of use: 5% for 4 consecutive days
2, the total amount of intravenous injection: 3g each dosage: 150mg/kg Use method: 5% for 4 consecutive days
3, oral (percentage) Total use: 0.2g/kg per dose: 0.2mg/kg Method of use: tablet
4. Total nasal use :600mg/ day each dosage :40mg/ day Method of use :10% aqueous solution
5, oral sublingual use total amount: 120mg/kg each dose: 120mg/kg Use method: tablet
6. Skin usage: 45% aqueous solution
On the other hand, due to the low hemolysis activity and surface activity of hydroxypropyl betacyclodextrin, it is not irritating to skin and muscle, even if the concentration of hydroxypropyl betacyclodextrin reaches 100mg/ml, it is not irritating when injected into the muscle. Hydroxypropyl betacyclodextrin is significantly superior to other cosolvents in these respects.
