Drugs Produced By Biotechnology

"KNOWLEDGE IS THE BEST MEDICINE"

Prepared by Mr. Sagar L. Vekariya Roll No : 64 (06PH83)

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Biotechnology???
According to United Nations Convention on Biological Diversity :- Any technological application that uses biological systems, living organisms, or derivatives thereof, to make or modify products or processes for specific use. OR United States Congresss Office of Technology Assessment defined biotechnology as any technique that used living organism to make or modify a product, to improve plants or animals or to develop microorganisms for specific uses.

Applications of Biotechnology
Red biotechnology is applied to medical processes. E.g.antibiotics,gene therapy,cloning,etc. Green biotechnology is agricultural processes. E.g. pesticide, Bt corn,etc. White biotechnology, biotechnology biotechnology applied to

also

known

as

industrial

Blue biotechnology is a term that has been used to describe the marine and aquatic applications of biotechnology, but its use is relatively rare.
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Drugs
1. 2. 3. 4. Altepase [Activase] Human Insulin [Humulin] Humatrop : Growth Hormone Hepatitis B [Recombinant HB(Merck) a Hepatitis B Vaccine]

 Alteplase (USAN,INN) [Activase]

What is alteplase?
Alteplase is an enzyme that occurs naturally in man and causes blood clots to dissolve. Man-made protein manufactured by recombinant DNA technology. The naturally occurring protein, known as tissue plasminogen activator (TPA), is made by ovarian cells from the Chinese hamster. Nevertheless, the amount that is given to patients is far greater than the amount naturally made by the body itself. Molecular formula: C2736H4174N914O824S45 (non-glycosylated) C2569H3894N746O781S40 (glycosylated) Sterile, purified glycoprotein of 527 amino acids. White to off-white, lyophilized powder.
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Altepase cont.

Manufacturing process
The secretion of the enzyme alteplase into the culture medium by an established mammalian cell line (Chinese Hamster Ovary cells) into which the cDNA for alteplase has been genetically inserted.

Phosphoric acid and/or sodium hydroxide may be used prior to lyophilization for pH adjustment.

Fermentation is carried out in a nutrient medium containing the antibiotic gentamicin, 100 mg/L.
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Altepase cont.

Mechanism of action
Alteplase

Fibrin-bound plasminogen

Endogenous tissue plasminogen

Plasmin (active form)

Fibrinolysis and dissolution of clots.

Altepase cont.

Indications:
1. Acute Myocardial Infarction 2. Acute Ischemic Stroke 3. Pulmonary Embolism 4. Thrombo-embolic disorders

Contraindications:
Because of increased risk of bleeding: Active internal bleeding History of cerebrovascular accident Recent intracranial or intraspinal surgery or trauma Severe uncontrolled hypertension Intracranial neoplasm, arteriovenous malformation

Altepase cont.

Adverse effects:
Bleeding Allergic Reactions Nausea Vomiting Fever

Drug Interactions:
With heparin and vitamin K antagonists, drugs that alter platelet function (such as acetylsalicylic acid, dipyridamole and Abciximab) may increase the risk of bleeding if administered prior to, during, or after Activase therapy.

Altepase cont.

Dosage Administration:
Activase (Alteplase) is for intravenous administration only. Extravasation of Activase infusion can cause inflammation.

Supplied as:
Sterile, lyophilized powder in 50 mg vials containing vacuum and 100 mg vials without vacuum.

Storage:
Store lyophilized Activase at controlled room temperature not to exceed 30C (86F), or under refrigeration (2-8C/36-46F). Protect the lyophilized material during extended storage from excessive exposure to light. Do not use beyond the expiration date stamped on the vial.
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 Humulin : Humulin
Humulin :
Humulin is the branded product of the famous pharmaceutical manufacturer, Lily, containing human-insulin and its host of variants, being produced by it in different countries across the globe.

Description about Insulin :

It is a pancreatic-hormone produced by the -cells of the islets of Langerthans of the pancreas and essentially comprise of two separate chains of amino acids, the A and B chains, joined together by two disulphide bridges. essentially involved in the regulation of blood-glucose concentrations And also specific role in the protein and lipid metabolism.
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Humulin cont

Types of Diabetes :

1. 2.

Diabetes incipidus Diabetes mellitus I. Insulin-dependent diabetes mellitus II. Non-insulin-dependent diabetes mellitus

Treatments :
The human, porcine, bovine or mixed porcine-bovine insulin

Insulin-dependent diabetes mellitus (control & management) Diabetic ketoacidosis (control & management) In some cases of non-insulin-dependent diabetes mellitus

Drawbacks :
Hypersensitivity reaction Hypoglycemia
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Humulin cont

Insulin produced by a variety of species

Same basic structure Different in sequence of amino acids

Type of insulin
Porcine insulin

Molecular Formula (M.W.) C256H381N65O76S6 [5777.6]

Comments
Differs from human insulin in only one amino acid in B-chain

Human insulin

C257H383N65O77S6 [5807.7] ------One A.A. in B-chain & Two in A-chain

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Bovine insulin

C254H377N65O75S6 [5733.6]

Humulin cont 1.

Five different types of insulins :

Conventional Insulin :
An extract of insulin- recrystallized it. - Other than insulin - A number of pancreatic peptides (e.g. glucagon, pancreatic polypeptide, somatostatin, etc.)

2.

Single-peak Insulin :
Gel Filtration - Reduction in the content of Pancreatic-peptides or insulin derivatives.

3.

Highly Purified Insulin :

Gel Filtration + ion-exchange chromatography -further lower the proinsulin and other peptides.

4.

Monocomponent Insulin :
In UK, Highly Purified Insulin product Known as this name.

5.

Purified Insulin :
Designated by FDA in USA, which containing less than 10 ppm of proinsulin. 15

Humulin cont

Several human insulin variants :

(Changed in A.A. sequences)
1. 2. Human insulin (emp) Human insulin (crb)
e.g. -Dalanted Insulin -Insulin Defalan -sulphated insulin Quite -Insulin Argine recently. -Insulin Lispro

Produced by r-DNA technology & Also known as Bio-synthetic insulin

3. 4.

Human insulin (prb)[Bacteria] Human insulin (pyr)[yeast]

Examples of Humulin :
1. Humulin 70/30, 80/20, 70/30, 60/40, 90/10, 50/50 2. Humulin I 3. Humulin L (insulin zinc suspension)
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Humulin cont

Formation of Proinsulin using Bacteria(E.Coli)

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 Humatrope

; Growth Hormone

Growth hormone : an anabolic hormone secreted by the anterior pituitary which stimulates growth and anabolism. - it affects fat, carbohydrate and mineral metabolism.

Somatropin USAN,INN Humatrope; Umatrope

synthetic human-growth hormone comprises of a single polypeptide chain of 191 A.A. having disulphide linkages between positions 53 = 165 & 182 = 189.

Different Preparations
epr :enzymatic conversion of specific precursor produced by a bacteria(Escherichia coli). rbe : from bacteria by r-DNA technology. rmc : from mammalian (mouse) cells by r-DNA technology.
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Humatrope cont
Somatropin is a synthetic human growth hormone; and Somatrem is its corresponding methionyl analogue.

Uses and Mechanism of Action:

Promotes :
the growth of muscular Skeletal Other tissues Stimulates proteins anabolism Also affects fat and mineral metabolism Carbohydrates metabolism

Pharmacokinetics :
Well-absorbed after S.C. or I.M. injection. (half-life 3-5hrs) Pediatric dose: 0.18mg/kg/week ; adult dose: 0.006mg/kg/day Phosphoric acid and/or sodium hydroxide may have been added to adjust the pH. Reconstituted solutions have a pH of approximately 7.5. This product is oxygen sensitive. Metabolized in the liver and excreted in bile. 19

Humatrope cont

Indications :
In pediatric

an inadequate secretion of normal endogenous growth hormone. Turner syndrome--whose epiphyses are not closed.
Adult

who have growth hormone deficiency either alone, or with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma

Contraindication :
pediatric patients with closed epiphyses. any evidence of active malignancy. with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma or to patients having acute respiratory failure. in patients with Prader-Willi syndrome

Side Effects :
Leukemia Injection site pain Transient edema 20

Humatrope cont

Storage :
At 2-8oC in perfect airtight containers in dosage forms not less than 2.5 units.mg-1. The bulk solution stored at -20oC in airtight containers.

Trade Names : Genotropin Humatrope Norditropin Nutropin Saizen Serostim

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Hepatitis B (Hepatitis B Vaccine)

Hepatitis B virus infects the liver of hominoid, including humans, and causes an inflammation called hepatitis. It is a DNA virus and one of many unrelated viruses that cause viral hepatitis. The disease, originally known as serum hepatitis.

Types of Hepatitis
Hepatitis A Hepatitis B Hepatitis C (no vaccine for HC) Hepatitis D (no vaccine for HD) Hepatitis E (no vaccine for HE)

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HBV cont
1a. How is HBV transmitted ?

Sex with an infected partner Injection drug use that involves sharing needles, syringes, or drugpreparation equipment Birth to an infected mother Contact with blood or open sores of an infected person Needle sticks or sharp instrument exposures Sharing items such as razors or toothbrushes with an infected person 1b. How is HBV not transmitted ? HBV is not spread through food or water, sharing eating utensils, breastfeeding, hugging, kissing, hand holding, coughing, or sneezing.
2.How long does HBV survive outside the body?

HBV can survive outside the body at least 7 days and still be capable of causing infection.

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HBV cont
3. What are the signs and symptoms of HBV infection?

Abdominal pain Fever Dark urine Fatigue Joint pain Loss of appetite Nausea Jaundice Vomiting Persons with chronic HBV infection might be asymptomatic
4. How likely is HBV infection to become chronic?

The risk for chronic infection varies according to the age at infection and is greatest among young children. Approximately 90% of infants and 25%50% of children aged 15 years will remain chronically infected with HBV. By contrast, approximately 95% of adults recover completely from HBV infection and do not become chronically infected.
5.How is HBV infection treated?

For chronic infection, no medication is available; treatment is supportive. For acute infection, several antiviral drugs like :

adefovir dipivoxil

interferon alfa-2b telbivudine

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 Hepatitis B Vaccination
1.Who should be vaccinated against hepatitis B?

All infants, beginning at birth & All children aged <19 years who have not been vaccinated previously Susceptible sex partners of hepatitis B surface antigen (HBsAg)-positive persons Susceptible household contacts of HBsAg-positive persons Healthcare and public safety workers at risk for exposure to blood or blood-contaminated body fluids Persons with end-stage renal disease, including predialysis, hemodialysis, peritoneal dialysis, and home dialysis patients Travelers to regions with intermediate or high rates of endemic HBV infection Persons with chronic liver disease Persons with HIV infection

2. Who should not vaccinated hepatitis B vaccine?

serious allergic reaction to a prior dose of hepatitis B vaccine.

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HBV cont
3. Can hepatitis B vaccine be given during pregnancy or lactation?

Yes. Hepatitis B vaccine contains no live virus, so neither pregnancy nor lactation should be considered a contraindication to vaccination of women.
4. Can hepatitis B vaccine be given after exposure to HBV?

Yes. After a person has been exposed to HBV, appropriate prophylaxis, given as soon as possible but preferably within 24 hours, can effectively prevent infection.
5. Are booster doses of hepatitis B vaccine recommended?

For hemodialysis patients, the need for booster doses should be assessed by annual testing for antibody to hepatitis B surface antigen (anti-HBs). For other immunocompromised persons (e.g., HIV-infected persons, hematopoietic stem-cell transplant recipients, and persons receiving chemotherapy), the need for booster doses has not been determined. For persons with normal immune status who have been vaccinated, booster doses are not recommended
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HBV cont

6. What are the hepatitis B vaccines licensed for use in the United States?

Single-antigen hepatitis B vaccines

ENGERIX-B RECOMBIVAX HB

Combination vaccines
COMVAX:
Combined hepatitis B-Haemophilus influenzae type b (Hib) conjugate vaccine. Cannot be administered before age 6 weeks or after age 71 months.

PEDIARIX:
Combined hepatitis B, diphtheria, tetanus, acellular pertussis (DTaP), and inactivated poliovirus (IPV) vaccine. Cannot be administered before age 6 weeks or after age 7 years.

TWINRIX:
Combined hepatitis A and hepatitis B vaccine. Recommended for persons aged 18 years who are at increased risk for both hepatitis A virus and HBV infections. 27

Hepatitis Virus

1. Genetic material is extracted from hepatitis virus

3. Gene that directs production of surface protein is located

4. Gene is removed from viral DNA and inserted into plasmid

5. Plasmids are inserted into yeast cells

Yeast

Surface proteins that provoke an immune response

2. Individual genes analyzed and identified 8. Results is a large quantity of pure surface protein particles that provoke an immune response

Plasmids containing gene for surface protein 6. Yeast is grown by fermentation. Cells reproduce and generate more surface proteins 7. After 48 hr yeast cells are ruptured to free surface protein. Mixture is proceed to extract and purify surface protein

9. Surface proteins are combined with preserving agent and other ingredients to make vaccine

A Schematic Diagram Illustrating a Genetically Engineered Vaccine

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References
Web sites
www.rxlist.com www.drugplus.com www.drugs.com www.wikipedia.com www.nlm.nih.gov

Books
Pharmaceutical Biotechnology By K.Sambamurthy, Ashutosh kar Pharmaceutical Biotechnology By S.S.Purohit, A.K.saluja, H.N. kakrani Essentials of Medical Pharmacology By KD TRIPATHI
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Thank You..

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Medical Terms Explained

Diabetes incipidus :- Deficiency of vasopressin in posterior pituitary hormone (ADH)
leading to excessive urine production.

Diabetes ketoacidosis :- it develops in the absence of insulin because of increase fat

breakdown to Acetyl Co-A, which ,in the absence of aerobic carbohydrates metabolism, is converted to acetoacetate and B-hydroxybutyrate (which cause acidosis) and acetone (a ketone).

Epiphysis: The spongy extremity of a bone, attached to it for forming a joint with the
similar process of another bone.

Prader-Willi syndrome who had one or more of the following risk factors: severe
obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection.

Leukemia :- Progressive disease of blood forming organs with abnormal accumulation of white corpuscles and its precursors in blood and bone marrow . Vaccine :- A suspension of inactivated or killed microorganism (bacteria, viruses or
rickettsiae) administered for the prevention, amelioration or treatment of infectious diseases.

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* Combined hepatitis BHaemophilus influenzae type b conjugate vaccine. This vaccine cannot be administered at birth, before age 6 weeks, or after age 71 months. Combined hepatitis B, diphtheria, tetanus, acellular pertussis adsorbed, inactivated poliovirus vaccine. This vaccine cannot be administered at birth, before age 6 weeks, or at age >7 years. Combined hepatitis A and hepatitis B vaccine. This vaccine is recommended for persons aged 18 years who are at increased risk for both hepatitis B virus and hepatitis A virus infections. Recombinant hepatitis B surface antigen protein dose. ** Not applicable. Adult formulation administered on a 2-dose schedule. Higher doses might be more immunogenic, but no specific recommendations have been made. 32 Dialysis formulation administered on a 3-dose schedule at 0, 1, and 6 months. *** Two 1.0-mL doses administered at one site, on a 4-dose schedule at 0, 1, 2, and 6 months.