Current Research Status of Atorvastatin Calcium

WEN Qi, LI Jun-li, YU Pei-ming

(College of Pharmacy, Henan University, Kaifeng 475004, China)

Current Research Status of Atorvastatin Calcium

WEN Qi, LI Jun-li, YU Pei-ming

(College of Pharmacy, Henan University, Kaifeng 475004, China)

Objective To investigate the current research status of atorvastatin calcium and to provide references for its further research and development. Methods Literature review and online data query were conducted to analyze the situation of research papers, registration and patents. Results and Conclusion Investigation reveals that a lot of research on atorvastatin calcium has been carried out in China. The research and registration grew continuously and it reached the peak in 2012. The number of patents presented an explosive growth from 2008.

atorvastatin calcium; registration; application; patent

Atorvastatin calcium is a new type of synthetic drug with high efficiency. The drug acts on the liver cells selectively, decreases the transform from HMG-COA to methyl dihydroxy pentanoic acid through inhibiting the hydroxy methyl glutaric acyl coenzyme A (HMG-CoA) reductase of liver competitively. It turns out that the drug can restrict the synthesis of endogenous total cholesterol, reduce low density lipoprotein cholesterol (LDL-C) in peripheral blood, decline apolipoprotein B-100 and triglyceride and improve beneficial high density lipoprotein (HDL-C) slightly[1].

Atorvastatin calcium tablets, whose brand name is Lipitor, which were produced from Pfizer Pharmaceuticals Ltd are used commonly in clinical preparation. The drug’s indication is primary hypercholesterolemia, mixed hyperlipidemia and hypercholesterolemia accompanied by atherosclerosis risk. Through the method of surveying literature and online data query, this article summarized the situation of atorvastatin calcium, which contained the study of literature, the situation of registration, acceptance and patents. Our purpose is to provide a reference for further research and development and innovative generic for relevant enterprises in China.

1 Data sources and study methods

This article retrieved through “atorvastatin calcium” theme which took “China National Knowledge Infrastructure (CNKI)” as literature platform. There are 1053 literatures in all from 1998 to 2013.Through screening and identifying the search results, we sorted out a total of 940 literatures about atorvastatin calcium. According to temporal distribution and distribution of research direction, we analyzed 940 literatures statistically.

This article used “State Food and Drug Administration (SFDA) Center for Drug Evaluation (CDE)” as retrieval platform to inquire catalogue of accepted varieties without limiting the year, the type of drug and the type of application. We got a total number of 294 for application and registration about Atorvastatin calcium[2]. According to the type and temporal distribution of application and registration, 294 records were analyzed statistically.

We registered CPIC retrieval system of patent database and set “atorvastatin” as key words, we got a total of 195 patents. The retrieval dates was June 10th, 2013. One patent was for utility model and the others were for invention[3]. This article analyzed the application of patent for invention statistically.

2 Results

2.1 Distribution of research literature

2.1.1 Temporal distribution of research literature

The literature research number of Atorvastatin calcium is on the rise as a whole. The largest number of literature research appeared in 2012. Although this articleonly retrieved literature for the first 6 months in 2013, there are some literatures have not yet entered the database, it is estimated that the literature number of 2013 will not be lower than that of 2012 and the literature research number will maintain the upward trend. Figure 1 shows the specific temporal distribution.

Figure 1 Temporal distribution of research literature about atrovastatin calcium

The present literature research number of atorvastatin calcium increased greatly and the fields of research expanded continuously from 2010. It was concerned with patent expiries of Lipitor at the end of 2011. Many colleges, pharmaceutical enterprises and clinical staff in China increasingly recognized the expansive overseas and domestic markets of atorvastatin calcium and the huge shock to the drug markets after Lipitor patent expiries.

2.1.2 Subject distribution of research literature

The number of literatures about clinical effect of atorvastatin calcium is the largest and it took up 65% of the total number of literatures. Drugs combination also belongs to the aspect of clinical research. It turns out that clinical application fields of atorvastatin calcium are more and more extensive and the research of clinical effects is increasingly deeper. The literatures number of adverse reaction about this drug is only 4% of the total number of literatures. It turns out that the aspects of adverse reaction about this drug have not become the point of the research. Specific distribution of research direction was shown in Figure 2.

2.2 The application situation for registration

Figure 2 Subject distribution of research literature about atrovastatin calcium

2.2.1 Temporal distribution of application for registration

The application situations for atrovastatin calcium registration started in 2011 in China. There are more acceptance notes in 2006, 2008, 2011 and 2012. The number of registration on this drug reached a peak in 2012. It turns out that many famous pharmaceutical enterprises have seen excellent efficacy and broad market of atrovastatin calcium. These enterprises started to apply and register this drug one after another. Specific temporal distribution of application for registration notes was shown in Figure 3.

2.2.2 Type distribution of application for registration

Figure 3 Temporal distribution of application for registration about atrovastatin calcium

We have gotten 294 notes of application for registration about atorvastatin calcium from Feb 26th, 2001 to June 25th, 2013. The application of raw material has 48 notes and the application of preparation has 246 notes

Figure 4 Type distribution of application for atrovastatin calcium registration

The temporal distribution of the type of applicationtherein. The type of application for registration notes about atrovastatin calcium was shown in Figure 4.As figure 5 shows, the number of the type of generic drug of atorvastatin calcium application increased rapidly in 2012. To a large extent, it is connected with patent expiries of Lipitor in Nov 30th, 2011.

Figure 5 Annual type distribution of application for registration about atrovastatin calcium

2.3 The application of patent

The number of patents application of atrovastatin increased annually. The number of patents application was the largest in 2008 and 2011 respectively. The number of patents application grew fast from 2008. It turns out that many famous pharmaceutical enterprises have quickened their pace of the patents application of atrovastatin. The specific temporal distribution of patent application was shown in Figure 6.

Figure 6 Temporal distribution of application of patent about atrovastatin calcium in China

The analysis of the technical classification of atrovastatin patent in China was shown in Figure 7. As Figure 7 shows, the patents of the aspects of A61K and A61P are the largest. It turns out that the patent researches mainly focused on preparation and manufacturing of compound in China.

Figure 7 Analysis of the main technical classification of patent about atrovastatin in China

3 Discussion

3.1 The situation of literature research

The literature research number of atorvastatin calcium is on the rise annually as a whole and it reached a peak in 2012. Although the literatures of 2013 have not been completed, according to this trend, we can predict that the literature research number of 2013 will not be less than that of 2012 and the number will maintain the upward trend. The literature research number of this drug increased greatly from 2010. It turns out that this drug has received more and more attention at present and many people have affirmed the value of it.

3.2 The situation of application for registration

The application for atorvastatin calcium registration started in 2000. The number of application has increased since 2001. Because of the Lipitor patent expiries at theend of 2011, the number of application about this drug at 2012, particularly the number of the type of generic drug application, presented an explosive growth and distanced itself from other type of drug application in quantitative terms. Based on estimation, the situation of application for registration about atorvastatin calcium will be the same in 2013. It turns out that many famous pharmaceutical enterprises have realized the large market after the part patent expiries of Lipitor and have quicken their pace of the generic drug application one after another.

3.3 The situation of patent

A part patents of Lipitor have expired which are produced from Pfizer Pharmaceuticals Ltd in Nov. 30th, 2011. For generic drug manufacturing enterprises, it is not only an opportunity but also a challenge. However, it is difficult for domestic drug manufacturing enterprises to produce several drugs which are approved by the international, such as Lipitor in the short term. In our country, the situation of atorvastatin patent presented an explosive growth from 2008 and reached peak in 2008 and 2011. The main technical classification of patent of this drug focused on preparation and manufacturing process of atorvastatin compound in our country.

3.4 Market prospect

Statins takes the leading position in many lipid regulators which sold well in international medical market. Atorvastatin calcium has crowned the world medical market for years and it has become a mature drug of lipid regulators market. The clinical effect of Statins has received general acceptance in the environment of the high morbidity of hyperlipemia.

The expansion of new indication’s field of Statins and the application of non-lipid-lowering thereof will improve the status of the drug in clinical and promote development of lipid regulators market. It is estimated that the climax of atorvastatin sales will last for some time.

4 Conclusion

The research situation of atorvastatin, which contained the study of literature and the situation of registration and patents, presents a substantial growth in the past three years. It shows that this drug still has big development prospects in our country. With the increase of aging population, the improving of people’s living standards and the fast rhythm of life, the morbidity of hyperlipemia is in high demand. It makes the prospects of this drug more expansive in domestic medical market. At present, there are only several drug manufacturing enterprises producing generic drug of atorvastatin. Domestic market is mainly dominated by Lipitor which are produced by Pfizer Pharmaceuticals Ltd. However, Lipitor’s price is the highest in several drugs about atorvastatin in domestic market. Therefore, drug manufacturing enterprises should quicken their paces in our country. On the basis of sufficient investigating and paying close attention to research situation of all aspects of atorvastatin, we should focus on studying crystal form and chemical synthesis of atorvastatin. Through, improving the manufactured technique and lowering the cost, we can produce the drugs which have fine quality and suitable prices in the near future.

[1]MENG Li-jun, WANG Wen-ying, DIAO Shu-ling.Clinical Application of Atorvastatin [J]. Practical Journal of Cardiac Cerebral Pneumal and Vascular Disease, 2007,15(4):325-327.

[2] Center for Drug Evaluation (CDE).Date query [EB/OL]. http:// www.cde.org.cn/news.do?method=changePage&pageName=servic e&frameStr=2013-06-27.

[3] Retrieval System of Patent Database of the China Patent Information center. Date query [EB/OL]. http://search.cnpat.com.cn/cprs2010/cn/ PatentGeneralList.aspx?No=999.1.194&Query=F%20XX%20(%E9 %98%BF%E6%89%98%E4%BC%90%E4%BB%96%E6%B1%80 %2FTX%2B%E9%98%BF%E6%89%98%E4%BC%90%E4%BB% 96%E4%B8%81%2FTX)&Nm=2013-06-10.

Author’s information: YU Pei-ming, Associate professor, PhD. Major research area: Pharmacy administration and regulations. Tel: 13223806998, Email: ypm@henu.edu.cn