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Development trend of chiral drug

Posted Date : 21/12/2011  Click : 918

  Chiral drugs in the design, research, development, and listing of new drugs is a major issue - 4] - [1. Three dimensional chemical structure is an important aspect of pharmacology [1]. In the past few decades, the dominant force in the pharmacopoeia is racemic, but since the advent of new technology in 1980, allowing significant amounts of pure enantiomers in pharmaceutical, awareness and interest in people of drug action of stereochemistry has increased [2-4].
Advances in stereo selective biological analysis have led to a new understanding of the importance of stereo selective pharmacodynamics and pharmacokinetics, and the relative contribution to the overall drug action has been different. When a of enantiomers for interested in the activity, and pairs of counterpart may be ineffective, with some activity of interest, activity of antagonists enantiomers may also want or do not want to separate activities [3-5]. Considering these possibilities, seems to be the main advantage of pure solid chemical drugs, for example, total dose reduced therapeutic window increase, reduce inter subject variability and dose-response relationship between more accurate estimation [3,4]. These factors lead to a growing preference for single enantiomers in the enterprise and some regulators. Chiral drug regulation began in the United States, in 1992 the United States published a formal policy on the development of chiral drugs, the paper's title is a policy statement of the new stereo isomer drug [6]. Then, in 1994, the European Union published a chiral active drug [7] began the regulation of rival drugs. The applicant must recognize the existence of chiral drugs in the drug, in an attempt to separate the stereoisomers, evaluate different stereoisomers of the different contributions to the activity of interest, and make a rational choice of listed stereoisomerism of the form.
Global sales of chiral drugs in the form of a single enantiomers continues to grow. Single enantiomer forms of medicine market share increased year by year, from 1996 27% ($744 billion) to 29% in 1997, 30% in 1998, 32% in 1999, 34% in 2000, 38% in 2001 to 2002 the market for estimation to 39% (151.9 billion dollar) [8 13].
Ranking top ten single enantiomeric drugs (annual sales of more than $1bn) is: atorvastatin (cardiovascular), (cardio vascular simvastatin, pravastatin sodium (heart blood vessel of), paroxetine hydrochloride (central Bible system), bisulfate clopidogrel (blood), sertraline hydrochloride (central nervous system), propionic acid fluoride for fluticasone and salmeterol (breathing), Esso esomeprazole magnesium (gastrointestinal), amoxicillin and clavulanate and clavulanate potassium (antibacterial), valsartan (cardio vascular of).
Previous reports of a limited range of chiral and non chiral drugs, each covering only a short cycle and limited to a single jurisdiction. Include the following example, from 1996 to 2000, UK Medicines Control Agency (MCA, now of the medicines and healthcare products Regulatory Agency (MHRA) of 95 to submit the new chemical entities (nces) an informal analysis evaluation [14], in the years 1998-2001. Analysis of new molecular entities (NMEs) is FDA approved.
This paper assesses and provides a perspective on the development of chiral and chiral drugs, and investigates the effects of this on industrial drug development and drug regulation around the world.
According to the characteristics of chiral drugs, the global distribution of drug approval
Overall, the 20 year period (1983-2002) was a single enantiomers over the non chiral drugs, and the DL represents a small number of categories, and the whole world was approved by the drug in 23%. Since 1998, a single to reflect the advantages may be single enantiomer drugs approved driven, in 1983 to 1986 during the 4 years, more of the racemic drug (32%) and single enantiomer drugs and non chiral drugs compared, more than all the chiral drugs. However, even in the early 1980s, single enantiomeric drugs not approved drugs and the approval of the minor components of chiral drugs, in the next few years, fly chiral drugs in the proportion of drug approval gradually decreased, from 43% to 34%. The proportion of non chiral drugs was 43:57 (1983-1986), 36:64 (1987-1990), 34:66 (1991-1994), 41:59 (1995-1998), and 34:66 (1999-2002). During the period of 1999-2002, the proportion of the foreign body decreased sharply in the period of 8%, compared with the earlier stage, and decreased gradually. The 2001 was not approved in 2002, and the two kinds of foreign dl were approved in (in Japan and South Korea). In 1998, the first 50% of the approved drugs were approved for the first time in, and the number reached more than 60% during the period of 2001-2002.
These trends are likely to be largely influenced by the regulatory body of the major jurisdictions, which is conducive to encouraging the development of single enantiomers beyond the [6,7]. Thus explaining this dramatic shift, pharmaceutical companies are more interested in the manufacture of more secure single enantiomers and non chiral drugs than have problems with the.
According to the characteristics of chiral drugs, the distribution of FDA approved drugs
From 1991 to 2002 years, the FDA approved drug distribution and worldwide distribution have something similar to that in the 12 years, 44% of single enantiomers in pharmaceutical, 42% of non chiral drugs and a small part of the racemic drugs accounted for about 14% of the. Every three years the distribution of single enantiomers of advantage is obvious, starting in 1991-1993 45%, from 1991 to 2002 years of the index changes is slight, however, this period of the racemate of serious decline. Non enantiomers from 35% to 1997-1999 between 52% and 1991-1993, and then 2000-2001 years under1 Eichelbaum, M., Testa, B. and Somogyi A., eds (2003) Stereochemical Aspects of Drug Action and Disposition , Springer.
2 Eichelbaum, M. and Gross, A.S. (1996) Stereochemical aspects of drug action and disposition.  Adv. Drug Res.28, 1-64.
3 Caldwell, J. (1999) Through the looking glass in  chiral drug development.  Modern Drug Discov.2, 51-60.
4 Agranat, I., Caner, H. and Caldwell, J. (2002) Putting chirality to work: the strategy of chiral switches. Nat. Rev. Drug Discov. 1,753–768.
5 Shah, R.R. (2003) Improving clinical risk/benefit through stereochemistry. In Stereochemical Aspects of Drug Action and Disposition (Eichelbaum, M., Testa, B. and Somogyi, A., eds), pp. 401–432, Springer.
6 Food and Drug Administration (1992) FDA’s policy statement for the development of newstereoisomeric drugs. 57 Fed. Reg. 22 249
7 Committee for Proprietary Medical Products (1993) Working parties on quality, safety and efficacy of medical products. Note for guidance: investigation of chiral active substances. III/3501/91
8 Stinson, S.C. (1998) Counting on chirality. Chem. Eng. News 76 (38), 83-104
9 Stinson, S.C. (1999) Chiral drug interactions. Chem. Eng. News 77(41), 101-120
10 Stinson, S.C. (2000) Chiral drugs.  Chem. Eng. News78(43), 55-78.
11 Stinson, S.C. (2001) Chiral pharmaceuticals.Chem. Eng. News 79(40), 79-97.
12 Rouhi, A.M. (2002) Chiral roundup. Chem. Eng. News 80(23), 43–50
13 Rouhi, A.M. (2003) Chiral business. Chem. Eng. News 81(18), 45-55
14 Shah, R.R. and Branch, S.K. (2003) Regulatory requirements for the development of chirally active drugs. In Stereochemical Aspects of Drug Action and Disposition (Eichelbaum, M. et al., eds), pp. 379–399, Springer.
15 Hilts, P.J. (2003)  Protecting America’s Health: the FDA Business, and One Hundred Years of Regulation. pp. 144–165. Alfred A. Knopf, New York.

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