water-soluble polysaccharides “ from nuts to soup ”

March 5, 2004. Southern Bio-products Conference

Water-soluble Polysaccharides “ From Nuts to Soup ”

Recent Advances Robert Y. Lochhead

School of Polymers & High Performance Materials

The University of Southern Mississippi


Outline

• Review Recent Advances In Polysaccharides– Focus on Applications – Focus on specialty high profit

• Medical

• Food

• Cosmetics


Cellulose Derivatives

• Sodium Carboxymethylcellulose

• Hydroxymethylcellulose

• Hydroxyethylcellulose– Hydrophobically-modified Hydroxyethylcellulose

• Hydroxypropylcellulose

• Hydroxymethylpropylcellulose


Removing Unpleasant Taste from Medicine

• Mask taste by quick disintegration:– Tablet with medication contains

• mannitol (to improve taste)

• Sodiumcarboxymethylcellulose (disintegrant)

• Sodium glutamate (Corrigent)

Koike, Masahiko; United States Patent Application20040033258, February 19, 2004

Assigned to TAKEDA PHARMACEUTICALS NORTH AMERICA, INC


Gum Karaya • Gum Karaya, (Sterculia gum),

– dried exudation of the Sterculia Urens tree and other species of Sterculia. – The tree is native to India.

• Complex polysaccharide – molecular weight as high as 9.500.000 – yields galactose, rhamnose and galacturonic acid on hydrolysis. – occurs as a partially acetylated derivative.– acid number varies from 13.4 to 22.7.

• Imparts stability – through binding and emulsifying properties


Bioadhesives.

• Mucous membranes – For example mucosa of the buccal cavity

– have a rich blood supply

– desirable site for topical administration of active agents for systemic delivery.

• Transmucosal delivery of active agents – avoids first-pass metabolism by the liver

– avoids poor uptake or inactivation in the gastro-intestinal tract .


Bioadhesives. • Actives that can be delivered via bioadhesives:

– steroids • estrogens, progestins and related compounds• androgens and anabolic steroids;

– non-steroidal anti-inflammatory agents• ketoprofen; diclofenac; propranolol; thyroid hormones;

– pH sensitive peptides and small proteins such as insulin and ACTH;

– physostigmine; scopolamine; verapamil; and gallopamil.– Local treatments to alleviate pain in the buccal cavity.


Bioadhesives. • Requirements for a successful bioadhesive device

– for topical administration of active agents – prolonged periods of time

• The release liner should be easily peelable from the bioadhesive portion• the bioadhesive portion must maintain intimate contact with the site of

application– For 1 to 24 hours – sufficiently adhesive and cohesive – controlled delivery of the active ingredients in wet and moist environments – non-toxic, non irritating– easily removable.


Bioadhesives. • Gum Karaya and Polyvinylpyrrolidone

– Improved bioadhesive– Excellent controlled release.

• Houze, David; Mantelle, Juan; Kanios, David; United States Patent Application20040018241, January 29, 2004,

• Assigned to NOVEN PHARMACEUTICALS, INC


Sulfated Polysaccharides


Carrageenan

• Carrageenan – obtained by extraction with

water or alkaline water of certain Rhodophyceae (red seaweed).

• It is a hydrocolloid– consisting mainly of the

potassium, sodium, magnesium, and calcium sulfate esters of galactose and 3.6-anhydro-galactose copolymers.

3 types:

Kappa, lambda, iota


Carrageenan

• 3 categories of meat:– pale, soft, and exudative (PSE)

• Due to postmortem generation of lactic acid

– dark, firm, and dry or non-exudative (DFD)

– "normal" meat • acceptable

• subjectively between PSE meat and DFD meat.

• Carrageenan + soy protein – Prevents occurrence of PSE meat

Keller, Heinz; United States Patent Application20040037930, February 26, 2004

Assignee: Rhodia Inc.


… However • Carrageenan may cause

stomach lesions, cancer• Wednesday, October 17, 2001By

Environmental News Network Strawberry cheesecake like this may be stabilized and thickened with carrageenan.

• Containers of pudding, ice cream, yogurt, or cottage cheese may include the ingredient carrageenan, a thickener derived from red seaweed. For decades, it has been presumed to be safe to eat, but new research from a medical doctor on the faculty of the University of Iowa shows that presumption may be wrong.

• Carrageenan is a water-soluble polymer, also known as a gum, that is used as a fat substitute

in processed meats and can be found in condensed milk and some soy milk products.

• "Evidence from animal models has demonstrated


Heparin • Heparin is a sulfated polysaccharide

– mean molecular weight of 12000-15000 daltons– isolated from the intestinal mucous membranes of

cattle, sheep and pigs– Treats motoneuron diseases

• amyotrophic lateral sclerosis• progressive spinal muscular atrophy• infantile muscular atrophy• primary lateral sclerosis

Stutzmann, Jean-Marie; Uzan, Andre; United States Patent Application20040038938

Assignee: AVENTIS PHARMACEUTICALS INC.


Sulfated Polysaccharides • Heparin acts as an anticoagulant by

accelerating the inhibition of thrombin and factor Xa by antithrombin

• Dermatan sulfate (DS), a sulfated glycosaminoglycan that has antithrombotic activity in laboratory animals

• The two are synergistic.

Hirsh, Jack;Johansen, Kristian; Weitz, Jeffrey I.; United States Patent Application20040038932


Curdlan Sulfate

• Sulfated polysaccharide– Sulfated polysaccharides are known to have

• anti-retroviral activity (JPA S62-215529)

• antimalarial activity (WO95/08334).


Hyaluronic acid

• Used extensively in eye surgery


Mucosal Membranes

• Mucosal membranes are lined by epithelial or endothelial cells having "tight junctions" – physiologically connect the enterocytes apically.

• Examples of membranes– located in or on the skin, ear, eye, nose, gastrointestinal tract

• (e.g., mouth, throat, esophagus, stomach, large intestine, small intestine, etc.), reproductive tract (e.g., vagina, uterus, etc.)

• Mucosa have limited permeability to therapeutic agents– especially if molecular weight > 500 daltons

• includes most peptides and proteins.


Sulfated chitin and chitosan to deliver actives

across mucosal membranes

• Sulphated chitinous polymer – a primary carrier

• delivers therapeutic agent across a membrane

Kydonieus, Agis; Elson, Clive; Thanou, Maya; United States Patent Application20040038870, February 26, 2004


Aloe Vera Polysaccharide • Aloe (Liliaceae) is a shrubby tropical/subtropical plant which

has succulent and elongate leaves.• Aloe barbadensis Miller (Aloe vera Linne) is the most widely

used for its therapeutic properties.• Aloe vera plants contain two major juice materials:

– yellow exudate • Contains a high concentration of anthraquinone compounds that has been used

throughout the centuries as a cathartic and for medicinal purges;

– a clear mucilaginous gel • used since ancient times to treat burns and other wounds• increases the rate of healing and reduces the risk of infection.

– Grindlay, D.; Reynolds, T., J. Ethnopharmcol. 1986, 16(2-3), 117-151; – Joshi, S. P., J. Med. Aromat. Plant Sci. 1998, 20(3), 768-773.


Aloe Vera Polysaccharide

• Aloe gel comprises a mucilage of polysaccharide substances.– Most are glucomannans, mannans or pectins

– polysaccharide fraction ("NP18298") having an apparent molecular weight above 2 million daltons is a powerful immunostimulant

• 0.015% of the original dry weight

• the most potent polysaccharide fraction characterized to this point

• potent for macrophage activation

Elsobly, Mahmoud; (Oxford, MS) ; Ross, Samir; (Oxford, MS) ; Pasco, David Stanley; (Oxford, MS) ; Pugh, Nirmal Derek; (Oxford, MS)., United States Patent Application20040038931, February 26, 2004,


Galactomannans


Guar Gum

• Guar is a native plant of India – principally for its green fodder

– pods are used for food and feed.

– It has soil-enriching properties since it is a legume.

– the primary importance of guar is the commercial value of its seed gum (galactomannan gum).

• Guar was introduced into the United States from India in 1903


Guar Gum

• Oilfield – Drilling fluids – Fraccing fluids – Tertiary enhanced oil Recovery


Locust Bean Gum • Locust bean gum

– obtained from the endosperm of the Carob or locust seed (Ceratonia siliqua).

– carob paste was used by Egyptians to treat bindings for wrapping mummies,

– by Greeks as laxative, – by Arabs as a weight standard. – Locust bean gum is currently

being produced in parts of Spain/Portugal, Italy, Greece, Cyprus, Algeria, Morocco, Israel and Turkey


Locust Bean Gum

• retards ice crystal growth • shows viscosity synergy with xanthan.


Galactomannans in Chemotherapy • Galactomannan is isolated from Gleditsia triacanthos or

Medicago falcata– Molecular mass of 40,000-200,000 D.– used to reduce toxicity of a therapeutic agent

• mixed with the agent prior to administration• chemotherapeutic agents are adriamycin or 5-Fluorouracil

• treats cancer • chronic leukemia, breast cancer, sarcoma, ovarian carcinoma, rectal cancer,

throat cancer, melanoma, colon cancer, bladder cancer, lung cancer, mammary adenocarcinoma, gastrointestinal cancer, stomach cancer, prostate cancer, pancreatic cancer, or Kaposi's sarcoma.

Klyosov, Anatole; Platt, David; United States Patent Application20040038935 ,

Assigned to Pro-Pharmaceuticals, Inc


Glucomannans to Treat Obesity

• Konjac (Amorphophallus konjac) is a plant– the tuber is the source of the konjac flour

• highly viscous sol of glucomannan and soluble starches when reconstituted in water.

• The principal soluble constituent is glucomannan – a polysaccharide comprised of D-glucose and D-mannose

• Also useful in industrial applications– films, oil drilling fluids and paints


Glucomannans to Treat Obesity

• Pharmaceutical compositions for treating obesity– a lipase inhibitor, (orlistat)– Glucomannan

• Prevents oily leakage

Bailly, Jacques; Martin, Rainer Eugen; Raab, Susanne; United States Patent Application20040033983 Assignee : HOFFMANN-LA ROCHE INC


Dextran

Colloidal Metals for Medical Diagnosis • For immunological assays

– colloidal metal particles for labeling biomolecules– must stabilize the biomolecule-coated metal particles – add stabilizing and blocking substance

• non-saturated, "sticky" sites on the particles are blocked. • aggregation of the particles is minimized• re-diffusion of the relevant biomolecule is reduced.• inert proteins are used

– But they are not versatile

• Core-shell crosslinked , water-soluble polymers• Core-shell particles stabilized with amino-dextrans

– No cross-linking needed– Facile processing, cheap, versatile

Sluka, Peter; Heimerl, Sebastian; Kuerzinger, Konrad; Fischer, Thomas; United States Patent Application 20040038431, February 26, 2004,


Alginate


Alginate

• Origin: – Seaweeds in Northern Waters

• Red Weeds– Phaeophycase

• Giant kelp – Macrocystis pyrifera


Alginate

http://213.151.132.39/Biomed.nsf/0/b2f1464fb38d059bc12566d7004d73e9?OpenDocument


Alginate ‘Egg Box’ Model

http://213.151.132.39/Biomed.nsf/0/b2f1464fb38d059bc12566d7004d73e9?OpenDocument

Grant, G.T., Morris, E.R., Rees, D.A., Smith, P.J.C. and Thom, D., FEBS letters, 32(1) (1973), pp195-198


Alginates for Improving Bread & Doughnuts

• Consumers prefer bread with a soft and glutinous mouth feel– Contains large amounts of gelatinized starch

• Cannot return its shape after cutting & slicing

– Addition of hydroxypropyl alginate• Confers shape retention and good mouth feel.

Takahashi, Toshihiro; Sugitani, Hiromi; United States Patent Application 20040033300, February 19, 2004, Assigned to KIBUN FOOD CHEMIFA CO., LTD.


Alginate Coacervates

• Gelled Alginate + Guar – Coating for fresh meat

• No crosslinking required

– Better than collagen• Need smoked cross-linking

Goorhuis, Johannes Gerardus Maria; United States Patent Application20040037922, February 26, 2004


Hydrogels and Superporous Hydrogels

• Interpenetrating networks of poly(acrylic acid) and a polysaccharide-: – alginic acid (sodium salt)– chitosan – sodium salt of carboxymethylcellulose– Pectin, starch– xanthan, Gellan– carrageenan, gum arabic, guar gum, ghatti gum, tragacanth

gum, pontianac gum, karaya gum, agar-agar– methyl cellulose, and hydroxypropyl methylcellulose

• … for enhanced elasticity


Hydrophobically-modified Polysaccharides

• polysaccharides partially modified by cholesterol.– stabilize liposomes for chemotherapy and

immunotherapy. – liposomes coated by polysaccharide derivatives

• improved drug carrier.


Hydrophobically-Modified Hydrophilic Polymers

• Outline– Hydrophilic polymers modified by hydrophobic

moieties– Combination of surfactant and polymer

properties in one molecule– Self-associate in aqueous solution to form

complex micellar structures


HYDROPHOBICALLY MODIFIED HYDROXYETHYL CELLULOSE

• Mol wt. = 300,000

• One cetyl group

• per 143 anhydroglucose residues

• Rigid backbone

• Huggins k = 2.63 indicates association eve in dilute solution – Nishikawa, Yekta, Pham Winnik, & Sau; Langmuir, (Dec, 1998),

14, 7119,



Nishikawa, Yekta, Pham Winnik, & Sau; Langmuir, (Dec, 1998), 14, 7119,


HMHEC EFFECT OF SDS

Nishikawa, Yekta, Pham Winnik, & Sau; Langmuir, (Dec, 1998), 14, 7119,

COMICELLIZATION



VISCOSITY

[SDS]

CMC

Landoll &Sau; ACS Adv. Chem Ser, 213; (1986) 343


Hydrophobically Modified Alginate


Hydrophobically-modified Polysaccharides


Conditioning Shampoos

• Cationic polysaccharides– Cationic hydroxyethyl cellulose, cationic guar,

chitosan– used in shampoos for

• disentangling of wet hair • improving hair’s softness after drying.

Dubief, Claude; Restle, Serge; Giroud, Franck; United States Patent Application20040038931, February 26, 2004 ,


Polymer-Surfactant InteractionPolymer-Surfactant Interaction

[cationic[cationicpolymer]polymer]

[anionic surfactant][anionic surfactant]

1:1 CHARGE1:1 CHARGE

CMCCMCCMCCMC

+ + + +


Summary

• A Brief (not all-inclusive) review of recent advance) in polysaccharides – Mainly medical and pharma– Cosmetics – Food – Commercial & oilfield


QUESTIONS ?

[email protected]


Pullulan

water-soluble polysaccharides “ from nuts to soup ”

Documents

gum karaya gum karaya

sterculia gum

pse meat

active ingredients

categories of meat

dfd meat

bioadhesive portion

unpleasant taste