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2 Current situation of medical biotechnology
There is a big gap between China's medical consumption level and the international level. China's annual per capita consumption is only l 16.87 yuan, accounting for 16% every year.
The extent of growth; The total sales of drugs is about 654.38+04 billion yuan (seven kinds of drugs), with an annual growth rate of 265.438+0%-22%, but imported drugs, joint venture drugs and
The share of domestic drugs in the domestic market is basically three points. China will become an export base for raw materials and a sales market for finished drugs, which is dangerous.
After joining WTO, machines will become more and more important. Therefore, accelerating the research, development and production of new drugs is an important national policy of our country.
L Genetic engineering drug China has approved the listing of genetic engineering drug: recombinant human stem cells.
Interferon alb (trade name: interferon, west Qin Luo), recombinant human interferon a2a (trade name: Fukangtai, Lefolong, Internet, Dean, Bell
Fen), recombinant human interferon et2b (trade name rifuning, Anfulong, Andafen, Anfulai, Longhua Nuo), recombinant human interferon, recombinant human interleukin.
Su -2 (trade name: Antruck, Deluxe, Silla, Lu Ying, Yue Kangxian, Onet, Intecon), recombinant human granulocyte colony stimulating factor.
(trade names are gelifen, granular surf, Jiliqiang, leijin Saiqiang, granular surf and perilysin), recombinant human macrophage granulocyte colony stimulating factor (quotient).
Product names are Terry, Ji, Genin, Rial and Libido), recombinant streptokinase rSK, recombinant human erythropoietin (product name is Ning,
Ebbio, Iprodine, EPO, Aixuebao, Ebenen), basic fibroblast growth factor (trade name Befuji), recombinant epidermal growth factor. At present, the products being studied in China include nerve growth factor.
NGF, CNTF, GDNF, BDNF, SOD, leptin (Le), antithrombotic drug design, IGF- 1, hGH antagonist, human insulin C peptide, hirudin, calcitonin, glucokinase, human IL-6, Fit3 ligand, human tumor angiogenesis inhibitor, bFGF, thrombopoietin, etc.
2.2 emblem biological fermentation (mat shed medicine
Genetic engineering medical antibiotics A variety of antibiotics such as propionyl spiramycin, midecamycin, mitomycin and meleumycin were studied. blue mould
Vitamins and Ve are important fermented products in China. Penicillin acylase and penicillin acylase gene engineering bacteria were immobilized by cell membrane reactor.
Production of 6- aminopenicillanic acid by large-scale cracking of penicillin C in the factory. Self-built genetically engineered bacteria ferment to produce cephalosporin C,
The number of fermentation units has increased to more than 2,800, which has been widely used. 7-ACA is the mother nucleus of semi-synthetic cephalosporin, and the import volume of 1997 is 4.
1 100 million yuan, two-step enzymatic conversion of hydrolyzed cephalosporin C to 7-ACA, and the genetic engineering bacteria of the two enzymes were successfully cloned.
The conversion rate of salt is 73.4%, and the purity of 7-ACA is over 90%. In addition, several antibiotics have been developed, such as tobramycin, rifamycin SV, mitomycin C and tylosin. Nicomycin X, ningnanmycin, gentamicin, agricultural antibiotic 66oB, etc. The sale of anti-infective drugs is only in the world.
It ranks second only to cardiovascular drugs, while anti-infective drugs in China have always ranked first, especially after opening the rural market. With the drug resistance of human body
Strengthen, new antibacterial requirements will become more and more urgent.
2.3 lanthanum medicine in animals and plants
This is an important field of traditional pharmacy. In addition to medicines, there are biological products, preventive drugs and nutritional products. At present, this industry has separation technology.
Backward technology, low output and scattered production. Some new progress has been made in the improvement of biotechnology, such as: in the modernization of traditional Chinese medicine, the genes, enzymes, biochemistry and structure-activity of natural plants were analyzed, the effective components of plants were extracted by biotechnology, and taxol, ginkgolides, artemisinin, shikonin, ephedrine and so on were industrially produced by plant cell reactor culture; Biological drugs such as monoclonal antibody, interferon, growth hormone, growth factor and enzyme are produced by animal cell reactor culture.
Biopharmaceutical is a developing field.
With the aggravation of obesity and aging, in addition to cardiovascular drugs, weight-loss and lipid-lowering drugs, diabetes drugs and anti-Alzheimer's drugs have also become best-selling products.
Medicine. With the accelerated pace of life, fierce competition and changeable situation, the incidence of mental illness in major countries in the world has risen rapidly, which has become a serious shadow.
In view of the new problems of people's quality of life, research and development and production of cardiovascular drugs, anticancer drugs, AIDS drugs, diabetes drugs, Alzheimer's drugs and
Psychotropic drugs become the focus. For most cities, the establishment of biopharmaceutical production enterprises,
Upstream research institutions are still relatively scarce, but from a strategic point of view, it is necessary to establish leading research institutions, leading development institutions, leading students, and have one or two "five-year plans"
Biopharmaceutical enterprises. The Ministry of Education and the State Planning Commission approved the "National Life Science and Technology Talents Training Base" established by 36 universities.
The general idea of "combination, four innovations and two matching" (namely: upstream and downstream combination, Industry-University-Research combination, domestic and foreign combination, and cross-combination of different disciplines; System innovation, mechanism innovation and mode innovation; Policy support, investment support) is worth learning.
3. 1 genomics and protein genomics
Pharmacogenomics is a field that uses human genetic information to guide the development of new drugs, and it is a study of heredity.
The diversity of individual differences on the specificity of medication, using known gene theory to study individual medication and optimize drug design, in clinical practice.
Compounds with potential toxicity have been found in the world, and the low-efficiency and high-toxicity drugs on the market have been improved through pharmacogenomics.
After the completion of the human genome project, genomics can provide xuexicn.com for human beings.
Strong evidence proves the correlation between gene activity and diseases, but in fact, most diseases are not caused by gene changes and gene expression patterns.
Complexity, the same gene may play completely different roles in different conditions and different periods, which cannot be answered by genomics.
, resulting in post-genomics and protein's proteomics. The process of completing life function is: DNA-+mRNA_ ten eggs.
White matter, in this process, a gene may encode several or dozens of different protein. Gene transcription produces protein precursors, which are then added.
Engineering and modification into active protein, through a series of transportation and positioning, can play a normal physiological role. Protein omics is the study of "a gene"
The full set of protein's expression ". By comparing and analyzing the protein group of normal individuals and sick individuals, we can find "disease-specific eggs"
White matter molecules have become the molecular target of new drug design.
3.2 Drug Screening and Combinatorial Chemistry
Drug screening refers to the process of screening bioactive compounds from many compounds according to specific biological indicators.
The first compound found was lead compound. There are two kinds of new drug screening: one is random screening (ordinary screening), that is, screening from completely unknown compound groups.
Searching for lead compounds; The second is directional screening, that is, designing new compounds according to known lead compounds to screen out compounds with better efficacy.
Things. The experience of natural compounds, animals and plants, and traditional Chinese medicine is a favorable condition for our drug screening.
Combinatorial chemistry is the combination of chemical synthesis,
The combination of computer design and computer technology can simultaneously produce many structurally related but orderly compounds, and then use highly sensitive raw materials.
Methods These compounds were screened at the same time, and their bioactive substances were determined, and then their structures were determined in order to find new compounds.
Lead compounds. Combinatorial chemistry includes the establishment of molecular diversity compound library, cluster screening (solid phase separation, solid/liquid two-phase) and the confirmation of active molecular structure.
33 gene diagnosis and gene therapy
Gene diagnosis mainly aims at gene detection of pathogens, tumors and genetic diseases, as well as eugenics and intractable diseases (related to genes and heredity) in modern cities.
Control is one of the advanced signs, and there is basically no prenatal diagnosis, so genetic diagnosis is established and accumulated while serving the society.
Prepare data for gene therapy. Gene therapy is to introduce functional genes into patients for expression, and its expression product, protein, plays a role in curing diseases. Genetic variation or defect can lead to various diseases and may be passed on to future generations. Gene therapy is to give genes.
Do an operation, also called "molecular surgery". Somatic cell gene therapy is the mainstream of current research.
3.4 Gene Knockout, Transgenic Animals and Bioreactors
Gene knock out gene knock out refers to the experimental design of a gene with known structure but unknown function at the molecular level.
Because removal (including site-directed mutation), and then observe the whole animal, infer the corresponding function, its technology mainly includes the construction of recombinant gene vector,
Transfer to the nucleus of a human recipient, screen the hit cells, transfer the cells to a human embryo, and make it grow into an animal in gene knockout.
Transgenic animals are a kind of animals that can stably integrate foreign genes into the chromosome genome through experimental introduction and can be passed on to future generations.
Things. From 65438 to 0974, American scholars obtained transgenic mice by microinjection for the first time, and transgenic animals have been widely used in basic research and disease animals.
Model establishment, production of medicinal protein, agriculture (production of transgenic livestock, such as hairless chickens) and other fields.
3.5 biochips and street sensors
Biochip is a continuous integration process using microelectronics, micromechanics, chemistry, physical technology, computer technology, sample detection and analysis.
Miniaturization. Include lab-on-a-chip, DNAchip, protein chip and cell chip.
Chip), tissue chip, etc. Biochip technology includes chip array structure, sample preparation, biomolecule reaction and signal detection and analysis, and mainly
Used in disease diagnosis, drug screening and gene sequencing, it will make great contributions to agriculture, food supervision, environmental protection and judicial expertise.
devote/dedicate/give oneself to
Biosensor has the characteristics of strong specificity, high sensitivity and fast response, and can be used for the metabolism of various biological products and the determination of intermediate products.
Non-biochemical substance Enzymes and cells used in biosensors can be reused. Biosensors use enzymes, immune system, tissues and organelles.
Or the whole cell is used as a catalyst to make an immobilized membrane, which is connected with physical and chemical instruments (chemistry, heat, light and sound waves) to convert physiological signals into physical and chemical signals.
Output, can be prepared into micro sensors and multi-parameter sensors. The United States invests about13 billion dollars every year in the research and development of biosensor technology and products. The combination of bioengineering and computer engineering has great industrial prospects.
3.6 Tissue Engineering and Organ Transplantation
Tissue engineering is the application of biological and engineering principles to research and develop artificial tissues that can repair and improve tissue damage or functional loss.
Or a new organ science. Cartilage, bone, tendon, skin and other tissues were successfully reconstructed, and composite tissues such as blood vessels and trachea were regenerated. The research on the regeneration of pancreas, liver and other tissues has made different progress, and the tissue engineering of ureter, urethra, esophagus, small intestine, kidney, blood vessels, blood cells and other tissues has also made some progress.
3.7 new drugs
Drugs used for treatment, prevention and diagnosis all serve human beings in a certain dosage form, and the authoritative view is that "it provides a new way of administration"
Almost as important as providing new drugs. "Drugs must be made into certain dosage forms, which can be used for treatment, prevention or diagnosis, as well as xuexicn.com of preparations.
4 Medical treatment 1l5 Bigong
Effectiveness, safety, rationality and accuracy all reflect the level of medicine and determine the effect of medication. Improve the curative effect of drugs and reduce drugs.
In order to reduce side effects and drug-induced diseases, higher requirements are put forward for pharmaceutical preparations, and new dosage forms and new preparation technologies are also exerting their strength.
More and more important.
4 Industrialization of biopharmaceuticals
Due to the gradual saturation of the drug market in developed countries such as Europe and America, the patent period of some best-selling drugs protected by patents is coming soon, and the development of new patented drugs is slow, ten major changes have taken place in the international drug market structure: biotechnological drugs have sprung up everywhere; generic drugs
The proportion of prescription drug sales soared, much higher than the average annual growth rate of the entire pharmaceutical industry in the world; Say "no"
The growth rate of prescription drugs (OTC) is also accelerating; In drug development, cholesterol control, congestive heart failure, schizophrenia, old age
In the fields of memory loss, Alzheimer's disease, diabetes, AIDS and various cancers, the research and development speed is accelerated and the market prospect is broad; In terms of pharmaceutical preparations and dosage forms, transdermal absorption and controlled release pharmaceutical preparations have broad prospects; In order to reduce the number of inpatients, reduce the burden of inpatient beds and save medical expenses, new drugs that change hospitalization into outpatient treatment are constantly on the market; The market for senile diseases and maternal and child medicines has developed rapidly; The development of preventive drugs, health care and nutritional supplements will continue to heat up; Natural drugs have great development potential; It is getting more and more difficult to develop new drugs.
Biopharmaceutical has the characteristics of high investment, high benefit, high risk and long cycle. A biopharmaceutical needs to invest a lot of money and technology in its early development.
Surgery, manpower, a few years later Drug approval and clinical trials also take several years, so the success rate of biological drugs is only 5%- 10%. But according to tradition
Compared with the pharmaceutical industry, it has the advantages of convenient large-scale production, high profit, simple production process, less manpower investment, no pollution and short production cycle. Once the new drug is successfully developed, the profit is huge. According to Ernst & Young's analysis, there are currently 0 new biotechnological drugs in the late clinical trial stage, and 240 new drugs will be listed in 2007. There are several problems in the development and industrialization of genetic engineering drugs.
Please pay special attention to:
(1) Choose a good project
The commercialization competition of new biotechnology is fierce, so all new discoveries have been applied for specialization except some achievements in the human genome project without patents.
How to obtain the right to use the patent is the first problem to be studied in the development of new drugs; Followed by market evaluation, some genetic drugs are suitable for the whole world, there are
It can only be used in some fields, and only the market that can be mastered is meaningful to enterprises; The third is the feasibility of the project, including the degree of maturity (there are
Drug certificate does not necessarily mean maturity), whether it can be industrialized, whether the process cost is low and environmental protection issues. , but also consider the re-development investment after acceptance.
The development direction of genetic engineering drugs;
(1) The development of major diseases such as nervous system, tumor, cardiovascular system, AIDS and immunodeficiency, such as peptide, protein and nucleic acid.
Biotechnology products. The development of this field will mainly focus on interferon, growth hormone and T-PA.
② A batch of biotechnological products, vaccines and diagnostic monoclonal antibodies with good market prospects have been selected for development, which has been completed in China.
Basic, development focus is on hepatitis B gene vaccine and monoclonal antibody diagnostic reagents.
③ The development of targeted drugs is mainly the development of anti-tumor drugs. Current treatment
Tumor drugs have the problem of "no distinction between the enemy and me", killing both cancer cells and normal cells. Directional therapy is aimed at this.
The problem is that the so-called targeted therapy is to use antibodies to find the target, just like the navigator of a missile, and introduce drugs into the lesion accurately without causing harm.
And other tissues and cells.
④ Development of humanized monoclonal antibody. Antibodies can fight against various pathogens and can also be used as guides, but the current monoclonal antibodies
Most of them are mouse-derived antibodies, which will produce antibodies (anti-antibodies) or stimulate immune response after being injected into human body. At present, phage antibody technology and embedding have been studied abroad.
Combining antibody technology and genetic engineering antibody technology to solve the humanized antibody problem.
⑤ The research and development of blood substitutes still occupies an important position. Blood products are made of a large amount of mixed human plasma, because human blood
It is inevitably polluted by various pathogens, such as HIV and hepatitis B virus, and cases in which patients are infected with AIDS or hepatitis B through blood transfusion.
This happens from time to time, so it is of great significance to develop blood substitutes through genetic engineering.
(2) Deal with the relationship among T, middle and lower reaches.
The human genome project is of great significance and far-reaching influence. With the initial completion of the more exciting "Human Genome Project" in post genome project.
The planning era of engineering research in protein is coming. The first benefit is preventive and therapeutic drugs and services for human health. Genetically engineered drugs
Extremes meet, but we must handle the relationship between the upper, middle and lower reaches.
(3) Establish an advanced engineering technology platform.
① drug screening platform ~ new drug discovery; ② drug pilot transformation platform; ③ Animal experimental platform.
(4) Strengthen biochemical engineering technology in biopharmaceutical development to ensure the diagnosis of human health and the discovery and preparation of new drugs for treatment.
It is through studying the interaction and recognition of biological macromolecules, through the interaction between exogenous drugs and external fields and the transmission and regulation of biological information, effective synthesis and biotransformation are carried out, and useful active substances found are prepared, extracted, separated and purified to obtain products beneficial to human health.
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(5) Intelligent biochemical process engineering
The research of biochemical engineering includes simulating basic biological reactions, biological surfaces and interfaces, mass transfer, heat transfer, momentum transfer, signal molecular transfer and
Reaction, engineering analysis of complex biological systems, etc. Biochemistry should actively absorb modern physics, mathematics and biology in the direction of intelligent chemical industry.
The latest achievements in science, computer and informatics. Intelligent chemical industry is aimed at generalized chemical processes, carefully designing new products and their reactions, separating and improving choices.
And process optimization control, using modern computers, intelligent instruments, system engineering and other new technologies, closely combined with computer control, related models and specialized.
Home system, local inspection points and actuators make the traditional chemical industry miniaturization, modularization and decentralization. I. e. through that multi-scale study of chemical process
Research integration and intelligent operation to solve the scientific problems of macro-level engineering and technology in the process of material transformation.
(6) Give full play to the role of the National Biochemical Engineering Center as a bridge and incubator.
The State Planning Commission and the Ministry of Science and Technology have allocated some funds for this institution.
Visit (pilot scale-up and engineering) R&D Institute-National Engineering Technology
Heart. 1996 The Ministry of Science and Technology was established in Beijing, Shanghai, Nanjing and Shenzhen respectively.
Biotechnology industry incubator-national biochemical engineering technology research center. In view of the fierce competition and high asking price of mature laboratories of genetic engineering drugs at home and abroad, and the heavy workload of perfecting the pilot scale-up test, Shenzhen National Biochemical Center uses the central equipment and talents.
First, the establishment of a genetic engineering laboratory for source project research not only saves a lot of money, but also gives full play to the potential of existing equipment.
Force, but also accelerated the speed of project development, is conducive to catching up with the international advanced level and market demand, but also conducive to the development of the center.
(7) developing CliO service industry
It is not easy for biotechnology and pharmaceutical companies to bring new drugs to market. A typical new drug application needs at least 4000 cases.
Bed tests sometimes require as many as 50 different tests. With more and more candidate drugs, the burden on the company is increasing. In order to reduce the time-to-market pressure of each drug, many biotechnology and pharmaceutical companies began to integrate external resources for drug development. Entrusted research institution
(CRO) has special expertise required by biotechnology and pharmaceutical companies, global and high-quality clinical practice.
The ability of trial management can meet the requirements of these companies for the time to market of new drugs. CRO mainly faces pharmaceutical and biotechnology companies, providing
Various professional services related to drug development. Now it has been extended to the discovery of drug lead compounds in the early stage and a series of services after the new drugs are listed.
Service. Such as drug discovery, preclinical research, pharmacogenomics, I ~ III clinic, informatics, clinical documents, policy and regulation consultation, production and packaging, promotion, marketing, product release and sales support, pharmacoeconomics and commerce.
Industry consultation, etc. Main references
1. Hebei Chemical Industry. 2004(4): 1-5
2 Modern Chemical Industry, 2004 (6): 1
3. Fine and Special Chemicals, 2004, 12 (2): 1-3.