Apocalypse of the innovation of dosage form to the market of Rayleigh peptide drugs

At present, the polypeptide drugs are mainly administered by injection The dosage forms are generally injection, suspension injection, powder injection, etc The new injection drug delivery system includes controlled-release microsphere injection, injection implant, infusion pump delivery system and PEG delivery system On September 22, AstraZeneca announced the official listing of 10.8mg noread (general name: goserelin acetate) in China It is a three-month long-term injection sustained-release implant, or it will provide more convenient and economic treatment for prostate cancer patients Relin drugs are a kind of synthetic peptide drugs based on GnRH structure, also known as luteinizing hormone releasing hormone (LHRH) When exogenous GnRH or its analogues are in physiological pulse frequency (every 90min Once) in the short-term low-dose administration, it can promote the pituitary gonadal system and be used to treat the symptoms of hypofunction, anovulation and delayed puberty; in the long-term high-dose administration with non physiological pulse frequency, it can inhibit the secretion of LH and FSH in the pituitary, resulting in the decrease of gonadal hormone secretion capacity and atrophy of sexual organs, and it can be used to treat some hormone dependent diseases , such as prostate cancer, leiomyoma, breast cancer, endometriosis and puberty precocious puberty   LHRH analogues are the first-line chemocastration drugs of choice for endocrine therapy of metastatic prostate cancer According to the competition pattern of endocrine therapy drugs in minenet-2011, the market shares of goserellin and triptorelin rank first   Peptide drugs are usually small in dosage, but need to be administered for a long time, which provides opportunities for innovative dosage forms Sustained release microsphere technology is to encapsulate the drug in the microsphere carrier, through subcutaneous or intramuscular administration, make the drug release slowly, change the process of transport in vivo, and extend the action time Triptoreline sustained-release microspheres, developed by Ipsen company of France, were first listed in 1986 Implants are divided into non injectable implants and injectable implants Non injectable implants implant drugs into the human body through surgery, and then the drugs can be released slowly and evenly in a long time At present, this method is commonly used for contraceptives The injectable implant is to mix and melt the drug and PLGA, then extrude them into strips by porous device, cut them into a certain length of about 1mm, sterilize them and put them into a special disposable syringe In the clinical direct subcutaneous or intramuscular injection, the drug will play a long-term role with the degradation of the skeleton material Injectable implants do not need to be implanted or taken out like non injectable implants, so they are easy to use and simple to prepare The computer-controlled infusion pump delivery system can achieve long-term and accurate drug delivery, which is a safe and effective way to treat chronic diseases The process of PEG modification is called PEGylation When protein and peptide drugs are combined with PEG with different molecular weight and different structure, the solubility and stability increase, immunogenicity and toxicity can be weakened, the half-life in vivo can be significantly prolonged, and the therapeutic index of drugs increases, so the effect is better At present, because of the high price and inconvenient use of the drug delivery system of infusion pump, there is no relevant product on the market in China, and the other three products are on the market However, there are only the first two kinds of peptide drugs Table 1 innovative dosage forms of Rayleigh peptide drugs on the market in China Drug name Light prolin Qu Puruilin Gore Sherry Lin Dosage form Microsphere controlled release formulation Sustained release implant Domestic manufacturers Shanghai Lizhu Beijing Bonte / / Foreign manufacturers Takeda Germany Fai Ling AstraZeneca   For patients with chronic diseases who need long-term treatment, the price of drugs and the convenience of application are the two most concerned aspects For triptoreline, the standard injection is 0.1mg/dose, the usage is 0.5mg/dose once a day for seven consecutive days, and then 0.1mg/dose once a day as the maintenance dose; the standard release agent is 3.75mg/dose, the usage is once every four weeks The price of common injection is about 80 yuan / dose, and the price of controlled release is 1850 yuan / dose From a long-term perspective, innovative dosage forms can save patients money and are easy to use In terms of market development, AstraZeneca is well considered For example, its specification is 3.6mg noread (goserellin acetate slow release implant), which has been ranked first in the market of endocrine therapy drugs Now it has launched the specification of sustainable release for three months On the basis of equivalence with the original specification, AstraZeneca has better tolerance, fewer injections, and monthly treatment costs 23% savings This is undoubtedly a better choice for patients Although the long-term dosage form has many advantages, the data of drug evaluation of minenet shows that the domestic enterprises are weak in the follow-up application, which is due to many reasons At present, China is in a critical period of enterprise transformation and upgrading, and innovation is the way of enterprise products and upgrading But the current situation is that the high-end field is occupied by foreign capital, the low-end products are not profitable, and most enterprises are still at a low level of repetition How to innovate and how to upgrade products is not only a matter of the manufacturers, but also related to the whole industrial chain As for the above sustained-release microspheres and sustained-release implants, the requirements for excipients are very high For various reasons, the upstream excipients manufacturers, as the preparation manufacturers, are difficult to obtain approval for injection level related excipients, leading to the basic shortage of domestic products, while the imported excipients are more expensive, thus inhibiting the enthusiasm of domestic drug research and development and production enterprises How to make products with high added value and get rid of the repeated phenomenon of low water products requires the government to increase its efforts to encourage innovation, and the whole industrial chain can only be realized through joint efforts (researcher Lily cha)