1.Introduction of Product
Hydroxycamptothecin was an anit-cancer agent which could obtain from the fruits of Camptotheca acuminata(Camptotheca acuminata was uniquely distributed in South China) or semi-synthesize from camptothecin.it was a novel and promising member of topoisomerase one inhibitors currently undergoing preclinical trials as an anticancer agent.Since 70's,Camptothecin had been used for therapy of several cancers, but it therapeutics was heavily restricted by their high toxicity, Hydroxycamptothecin was a high eutherapeuticity and low toxicity anit-cancer agent from camptothecin by chemical structure modification and obtained the remarkable curative effect in clinic. The findings of its inhibition to topoisomerase I of recent years had got great attention of international experts, and it had already become another focalization of anti-cancer research.
Hydroxcampththecin could inhibit topoisomerase I in its normal function of re-jointing the broken DNA chains,and furtherly caused the rupture of single DNA chain, inhibited the duplication of DNA, interfered the cell cycle (inhibit S Cyc, prolong the G2 Cyc), so as to the rupture & degradation of chromosome DNA and finally induced the perishment of cancer cell.
Hydroxycamptothecin had a good clinical curative effects towards Gastrointestinal cancer,Liver cancer, Head and Neck cancer and Lung cancer, so it was got welcome and recognition in clinic. It had a broad expectation and was listed as basic drug of the state.
Currently,the preparation of hydroxycamptothecin in the market were mainly injection,including liquid injection & lyophilized injection. When used to therapy of cancer patient,it caused the partial anti-cancer effects through systemic treatment,the dosage and toxicity were high,the lungs cancer patients were also treated through systemic treatment,if gathered the Hydroxycamptothecin at the lungs cancer part effectively.would be able to reduce the toxicity and side-effect effectively in treatment of lung cancer,achieved highly effective and the low toxicity veriestly.
The powder inhalation was a preparation that the drugs were prepared to the ultra thin powder and the thin powder for a carrier vehicle for the administration of drugs and mixed equably, Administered the drugs through a special equipment,the patients could inhale the drug into lungs on their own initiative,obtained The therapeutic effects, compares with the aerosol,The powder inhalation had more merits:
(1)The drugs could be administrated on patient's own initiative;
(2)They could avoid to pollute the atmospheric and to stimulate respiratory tract because of no the projectile of Freon;
(3)The drugs were administrated by the capsule form,the dosage was accurate;
(4)With no antiseptic and ethyl alcohol;(5)Better patients'compliance in thetreatment;
(6) the local action medicine, reduced the medicine dosage, poisonous and side effect, the security was high.
2.Goal of The Invention
The invention provided a kind of hydroxycamptothecin powder inhalation which the drug was administered through a special equipment and entered the respiratory tract by dryness-power,the drug could be preserved in the lungs for long times, achieved the therapeutic goal of the target, high efficient and safety.
The hydroxcampththecin powder inhalation which was stated in this invention was composed by following ingredient(percent by weight): hydroxcampththecin(1-100%), carrier vehicle(0-99%). After mixed equably,the hydroxcampththecin and the carrier vehicle which was ultr-micronization,was put into the powder inspiration installment(example: glutin, plastic capsule and bubble) by the single dosage form,the advantageous dosage was 100ug to 10mg,or the powder was contained in the multi-dosage does in the powder inspiration installment by the storehouse form.
The above hydroxcampththecin powder inhalation measured up the related national standard substance,carrier vehicle including:glycin,Aspartate,propionic acid,tryptophan,isoleucine,threonine, glutamic acid,phenylalanine,leucine,cystine,proline,tyrosine,mannitol,dextran,glucose,sucrose,
fructose, mannose and so on.
The dryness-powder of hydroxcampththecin were allowed to have the average diameter of 100um at most, the advantageous diameter was 1-10um,usually 1-50um. the dryness-powder of carrier vehicle were allowed to have the average diameter of 300um at most, the advantageous diameter was 100um,usually 10-100um.
The micronization described in this invention shatter could be processed by the fluid bed supersonic flow,high speed grinding,machinery grinding such as muller and so on,it also could be processed by recrystallization from the solvent.
When the compound which was inhaled from the single-dosage capsule inhalator inspiration,the dosage of hydroxcampththecin in the capsule was able to 100ug-10mg, advantage was 1-5mg, the dryness-powder mixed with the above carrier vehicle was 10-100mg,the advantage was 20-30mg