Ring-opening Polymerization (II)

1
Ring-opening Polymerization (II)
2
Cyclic Ethers
polymerization
difficult (substituents usually will prevent it)
unreactive
tertrahydropyran
dioxane
3
Cationic Polymerizationof Cyclic Ethers
oxonium ion
3) Oxetane
?-carbon is electron deficient
propagation
4
Need EnergeticThermo Plastic Elastomer
5
Cationic Polymerizationof Cyclic Ethers
4) THF (initiated by (preformed) oxonium ions)
triethyloxonium- tetrafluoroborate
Poly(THF)
6
Cationic Polymerizationof Cyclic Ethers
Difunctional PTMO (initiated by triflic
anhydride)
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Cationic Polymerizationof Cyclic Ethers
Difunctional PTMO (initiated by triflic
anhydride)
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Cyclic Amides
Referred to as ß-propiolactam ?-butyrolactam d-v
alerolactam e-caprolactam
n 2 3 4 5
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Why Caprolactam?
oxime
Beckmann Rearrangement
10
Nylon 6
aminocaproic acid AB monomer Polycondensation
- H2O
Nylon 6
8 10 monomer Need to extract with water
11
Anionic Initiated Polymerization
12
Anionic Initiated Polymerization
13
Anionic Ring Opening Polymerization of
Caprolactone
R- or RO-
Acyl oxygen cleavage
High polymer
14
Polylactic Acid (PLA)

• PLA belongs to the family of aliphatic polyester,
  and it is considered biodegradable and
  compostable. (i.e. ability of degrading a
  material under the action of microorganism in a
  humid environment to produce biomass and carbon
  dioxide)

• PLA is a thermoplastic, high strength, high
  modulus polymer which can be made from annually
  renewable resources to yield articles for use in
  either the industrial packaging field or the
  biocompatible / bioabsorbable medical device
  market.

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Polylactides
Derived from fermentation of carbohydrates
Cyclic dimers
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Method to produce High-Molecular-Weight (PLA).
Chain Coupling Agent
Low Molecular Weight Prepolymer Mw2,000 10,000
Azeotropic Dehydration Condensation -H2O
High Molecular Weight Prepolymer Mwgt100,000
Lactic Acid
Ring Opening Polymerization
Lactide
Low Molecular Weight Prepolymer Mw1,000 5,000
17
Polylactides
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Ring Opening Lactide Polymerization
1) Cationic Polymerization

1. Protic Acid (HBr, HCl, triflic acid, etc)
2. Lewis acid (ZnCl2 AlCl3, etc)
3. Alkilating or Acylating agents (Et3OBF4, etc)

2) Anionic Polymerization
Proceed by nucleophilic reaction of the anion
with the carbonyl and the subsequent acyl-oxygen
cleavage, this produces an alkoxide end group
which continuous propagate.
3) Coordination / Insertion Polymerization
Use less reactive metal carboxylates, oxides, and
alkoxides. Polymerization by tin, zinc,
aluminum, and other heavy metal catalysts with
thin (II) and zinc yielding the purest polymers.
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Anionic Polymerization
O
RO-M
CH3
H
O
O-M
RO
CH3
O
M. H. Hartmann, Biopolymers from Renewable
Resources, (1998)
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Coordination / Insertion Polymerization
CH3
O
O
Int. Product
R
O
O
O
CH3
H
Sn
Int. Product
Oct
O
CH3
O
Int. Product
OR
OH
CH3
O
Int. Product
Int. Product
Int. Product
Reaction mechanism. Du et. al (1995)
Macromolecules
21
Main Producers
Producer 2000 Million lb/yr 2001 Million lb/yr 2002 Million lb/yr
Cargill Dow LLC 16 300 300
Mitsui Chemicals 1.3 1.3 1.3
Cost US / lb 1.5/2.0 1.0 0.5
Chemical Week V162, 2000 Plastics Week,
Jan17, 2000 http//www.cdpoly.com/release.asp?i
d87
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Definitions of a Degradable Polymer

• Biodegradable
• a polymeric matrix that is degradable by
  enzymes
• Bioabsorbable
• a polymer that is degradable by other chemicals
  in the body

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Degradation
Hydrolysis and cleavage of the ester linkage
High Molecular Weight Prepolymer Mwgt100,000

Low Molecular Weight Prepolymer Mw2,000 10,000
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Degradation(Hartmann, M. Whitemann, N. )
Temp, ºC RH, Fragment Onset Biodegradation Complete
4 100 5.3 yr 10.2 yr
25 20 2.5 yr 4.8 yr
25 80 2.0 yr 3.1 yr
40 80 5.1 months 10 months
60 20 1.0 months 2.5 months
60 80 15 days 2 months
Hartmann, M., Whiteman, N. Polylactide, a New
Thermoplastic for Extrusion Coating. Mobley.
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Factors Which Affect Polymer Degradation

• Chemical composition.
• Distribution of repeated units.
• Presence of unexpected units or chain defects.
• Stereochemistry.
• Molecular weight.
• Molecular weight distribution.
• Morphology (amorphous/semicrystalline).

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The Ideal Polymer for Degradable Implants and
Drug Delivery

• A degradable polymer the polymer matrix should
  degrade into smaller fragments over a period of
  time, which then can be excreted from the body
• The degradation products of the polymer should
  not contain or become toxic materials for the
  body
• (An ideal mechanism for release of the drug
  should be at a constant rate )

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Factors that AcceleratePolymer Degradation

• More hydrophilic backbones and/or endgroups.
• More reactive hydrolytic groups in the backbone.
• Less crystallinity.
• More porosity.
• Smaller size device.

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Polymeric drug delivery

• Drugs are embedded in a polymeric matrix so that
  they may be protected from reactions by enzymes
  and body chemical substances that can destroy the
  drug chemistry before it reaches the targeted
  areas.
• The polymeric matrix also functions as a time
  controller in the concentration of active
  ingredient release.

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Polylactides

• Biodegradable Polymer Wafer
• Roughly the size of a dime, biodegradable
  polymer wafers (right) can be implanted in
  specific places in the brain after cancer surgery
  to deliver cancer-killing drugs at a controlled
  rate. (Photo courtesy of Guilford
  Pharmaceuticals)

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Balloon Angioplasty
Balloon Angioplasty without stent
Balloon Angioplasty with stent
From http//www.Angioplasty.org
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Problems With Stents

• Restenosis - A condition in which a stented
  artery becomes clogged with scar tissue that has
  grown through the mesh in a stent.
• Current Treatment - Occasionally doctors can
  perform a second balloon angioplasty, but there
  is a risk of the second balloon getting snagged
  on the old stent. The most common treatment for
  restenosis is to insert a drill-like instrument
  into the clogged artery, which is much more
  invasive than angioplasty.

Rotoblation
Cutting Balloon
Pictures from www.clevelandclinic.org
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2nd Generation Stents Drug delivery Coating on
Metal Stents

• STENT DESIGNBiosensors highly successful
  S-Stent/RX1 delivery platform featuring uniform
  strut geometry for optimized drug distribution,
  to which has been added an ultra-thin,
  proprietary resorbable polymer coating containing
  the drug.
• DRUG TYPE EVEROLIMUSA Rapamycin analogue
  previously studied for organ transplant
  applications, possessing potent smooth muscle
  cell immunosuppressive and anti-proliferative
  properties.
• INHIBITION OF RESTENOSISThe drug eluting stent
  eliminates restenosis compared to bare metal
  control stents implanted in pigs using the
  coronary overstretch injury model.

http//www.biosensors.com.sg/challenge/MainPage.ht
ml
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3rd Generation Stents Totally Bioabsorbable,
Drug-Eluting Stents

• Make the stent entirely from a bioabsorbable
  material
• No chest full of metal
• Structural support only needed for months
• No prolonged blocking of vessel branches
• Higher drug loading possible
• MRI delivery/monitoring possible
• Other applications