ANTI MICROBIAL AGENTS

These are the chemicals & their preparations used in reducing or preventing infection due to microorganisms.

Antiseptic: Inhibit the growth of MO (used for the living objects)

Disinfectant: Destroy the Pathogenic MO (used for non-living object)

Germicides: Kill Bacteria, Fungi, Viruses, Spores

Bacteriostatic: Primarily inhibit the Bacteria – Only arrest their growth not kill them.

Mechanism of Action of Antimicrobial

1. Oxidation
2. Halogenation
3. Protein Precipitation
4. Astringents

Oxidation:

Antimicrobial agents that function through oxidative mechanisms are hydrogen peroxide, metal peroxides, permanganates, halogens like chlorine, iodine, and certain oxohalogens anions. They act on the –SH group in cysteine present in most proteins to form a disulphide bridge between two – SH group. Which alters the specific function of the protein in the microorganism and overall change is responsible for the ultimate destruction of the microorganism.

Halogenation mechanism

This category of agents act on peptide linkage and alter its potential and property. The destruction of specific functions of protein causes the death of microorganisms. Most of the enzymes are proteinous in nature.

Peptide linkage undergo chlorination with change in molecular shape & ultimate destruction of the protein of microorganism.

Protein Precipitation

Many metal ions exhibit protein binding or protein precipitation. The nature of interaction with protein takes place through a polar group of protein which act as ligand and metal ions as a lewis acid. The complex formed may be strong chelate giving rise to the inactivation of the protein.

Astringents

Transition metal cations have protein precipitating action. But if a very dilute solution of such metal cations do not destruct protein & causes shrinkage or firming up skin or mucous membrane. This is called astringent action.

Use of Astringents

• Constriction capillaries & small blood vessel as styptics.
• Reducing the volume of exudate from wounds & skin eruptions.
• As Anti-perspirants- constrict skin pores & destroying body odour producing MOs.

Classification of Anti-Microbial Agents

1. Iodine Preparation & Compounds
   • Iodine & Iodine solution
   • Povidone-Iodine
2. Oxidizing agents
   • Hydrogen Peroxide,
   • Potassium Permanganate
   • Zinc peroxide
   • Sodium hypochlorite
   • Chlorinated water
   • Sod. perborate
3. Protein Precipitant
   • Silver nitrate
   • Mild Silver Protein
4. Mercury Compounds
   • Yellow mercuric oxide
   • Ammoniated Mercury, Mercuric Chloride
5. Sulphur & Sulphur compounds
   • Sublimated sulphur
   • Precipitated sulphur
   • Sulphur dioxide
   • Selenium sulphide
   • Cadmium sulphide
6. Arsenic Compounds
   • Carbarsone
   • Glycobiarsol
   • Tryparsamide
7. Antimony Compounds
   • Antimony Sodium Gluconate
   • Sod. Gluconate
   • Stibophen
8. Acids
   • Boric Acid

Iodine Preparation & Compounds

Iodine

Mol formula: I₂ ; Mw: 253.8

Iodine is widely used as a disinfectant and antiseptic, frequently in a solution of alcohol and water containing potassium iodide. Several compounds of iodine, such as iodoform (CHI₃), also serve as antiseptics.

• Iodine: It is found in Sea-water (traces) & Seaweeds Laminaria digitata.
• Any preparations which provide free Iodine are bactericidal, fungicidal, amoebicidal & virucidal.

Preparation

Iodine is manufactured by extracting kelp (sea weed ash) with water and the solution is concentrated. The sulphate and chloride of sodium and potassium are crystallized out, leaving soluble sodium and potassium iodides in the mother liquor. Sulphuric acid is added to the mother liquor and sulphur which is liberated from small amount of thiosulphate and sulphide is allowed to settle. The mother liquor is decanted and to this MnO2 is then added and the Iodine is distilled out.

2NaI + 3H₂SO₄ + MnO₂ → MnSO4 + 2 NaHSO₄ + I₂ + 2H₂O

Impurities like I Cl, I Br and I CN are removed by heating crude iodine with potassium iodide.
ICl + KI → KCl + I₂

Physical Property

It combines directly with some non-metals and with many metals.
2P + 3 I₂ → 2PI₃
Fe + I₂ → FeI₂
Reducing agent reacts with aqueous iodine solution and gets oxidized.
H₃ASO₃ + I₂ + H2O → 2HI + H₃ASO₄
H₂S + I₂ → 2HI + S
Iodine reacts with alkali to form an iodide and iodate when heated.
3I₂ + 6NaOH → 2NaI + NaIO₃ + 3H₂O

Potassium iodide dissolves large quantity of iodine in water, because of the formation of poly iodide. (I₃−)
KI + I₂ → KI₃

Assay

It is estimated by addition of potassium iodide solution, and acidified with acetic acid and titrated with sodium thiosulphate using starch mucillage as indicator. The end point is appearance of blue colour.

2Na₂S2O₃ + I₂ → 2NaI + Na₂S₄O₆ Sodium Tetrathionate

Incompatiability

It oxidizes hypophosphite, sulphite, some metals and reducing agents and iodine itself gets reduced to iodide. It reacts with ammonia or ammoniated mercury to form explosive iodide or nitrogen.

Storage

It is volatile at room temperature and reacts with rubber and corks. So it should be stored in amber colour bottles with tight glass stopper and kept in a cool place.

Povidone Iodine/PVP – IODINE/ Polyvinyl Pyrrolidone – Iodine Complex

• Povidone iodine is a complex of iodine with a polymer povidone. Povidone a polymer of polyvinylpyrrolidone/PVP.
• It is a complex of polyvinyl pyrrolidone and iodine containing not less than 9% and not more than 12% W/V of available I₂ (iodine).
• Povidone-Iodine is a complex produced by interaction between iodine and poly(2-oxopyrrolidin-l-ylethylene).
• Povidone-iodine belongs to Iodophores class of compounds. Iodophores are complex of iodine with career organic compound serving as a solubilizing agent, which slowly liberate iodine in solution.

Property

• It is Non-staining preparation & can be washed clear from skin & Cloths
• Yellowish brown amorphous complex
• Non-irritating & low oral toxicity

Storage

• Air-tight containers

Uses

• Topical Antiseptics
• Major advantages over other iodine preparation is lack of tissue irritation. Solutions are used for surgical scrubs and for pre operative antisepsis for the skin.
  It is also used in gargles and mouth washes for the treatment of infections in the oral cavity.

Povidone-Iodine Solution

• Povidone-Iodine Solution is a solution of Povidone-Iodine in Purified Water. It may contain a small amount of Ethanol.
• Usual strengths. 5 per cent w/v; 7.5 percent w/v; 10 per cent w/v.

Read more Various Iodine Solutions click here

Oxidizing agents

Hydrogen Peroxide: (20 Vol)

Chemical formula: H₂O₂
Molecular weight: 34.016

Hydrogen Peroxide Solution (20 Vol) is an aqueous solution of hydrogen peroxide. It may contain a suitable stabilising agent. Hydrogen Peroxide Solution (20 Vol) contains not less than 5.0 per cent w/v and not more than 7.0 per cent w/v of H₂O₂ corresponding to about 20 times its volume of available oxygen.

Hydrogen Peroxide Solution (100 Vol)

Strong Hydrogen Peroxide solution: 27 % w/v of H₂O₂.(Also Known as Strong Hydrogen Peroxide Solution or Hydrogen Peroxide Solution (100 Vol))
Hydrogen Peroxide Solution (100 Vol) contains not less than 26.0 per cent w/w and not more than 28.0 per cent w/w ofH20 2, corresponding to about 100 times its volume of available Oxygen.

Preparation

It is prepared by adding a paste of barium peroxide in ice cold water to a calculated quantity of ice cold dilute sulphuric acid. The insoluble barium sulphate is filtered off.

BaO₂ + H₂SO₄ → BaSO₄ (ppt)+ H₂O₂

It is also manufactured by electrolysis process. Electrolysis of sulphuric acid to peroxy sulphuric acid which is hydrolyzed to give the product. Sulphuric acid is oxidized to give peroxydisulphuric acid (H₂S₂O₈)

Oxidation

2H₂SO₄ → H₂S₂O₈ + H₂ (Gas)

Hydrolysis

H₂S₂O8 → H₂SO₅ + H₂SO₄ (Peroxy sulphuric acid)
H₂SO₅ + H₂O → H₂O₂ + H₂SO₄

Properties

Hydrogen peroxide solution is a colourless liquid with slightly acidic taste. The solution is decompases in contact with oxidisable matter, reducing agent, when made alkaline or even on standing.
2 H₂O₂ → 2H₂O + O₂ (gas)
The solution is stabilized by the addition of small amount of acid and adjusting the pH between 2 and 3. Polyvalent metal ions catalyse decomposition of hydrogen peroxide and complexing agent prevent it by acting as stabilizer.

Hydrogen peroxide acts as oxidizing or reducing agent depending upon the chemical environment.
In oxidation reaction (in acidic medium) it accepts two electrons.
H₂O₂ + 2H+ + 2e- → 2H₂O
In reduction – release of two electrons.
Decolourisation of permanganate solution.
5 H₂O₂ + 2KMnO₄ + 3H₂SO₄ → K₂SO₄ + 2MnSO₄ + 8H₂O + 5O₂

Assay

It is estimated by titration with potassium permanganate in presence of 4 N sulphuric acid. Potassium permanganate is reduced to manganese sulphate. This determination depends on mutual oxidation – reduction as expressed by following equations.
2KMnO₄ + 3H₂SO₄ → K₂SO₄ + 2MnSO₄ + 3H₂O + 5(O)
H₂O₂ + (O) → H₂O + O₂
Hydrogen peroxide is oxidized to oxygen by nascent oxygen produced from the reaction between potassium permanganate and dilute sulphuric acid. The appearance of permanent pale pink colour indicates the end point.

Storage

It should be stored in light resistant container in a cool place.

Use

1. Used as an Antiseptic and topical Anti-infective.
2. It arrests the bleeding of wounds.
3. It is used to clean the wounds and ears

Potassium Permanganate

Mol. formula: KMnO₄; Mw: 158.034 g/mol

Preparation

Manganese dioxide is fused with solid potassium hydroxide along with potassium chlorate, a green mass potassium manganate is obtained. The mass is cooled is extracted with water and filtered.
3MnO₂ + 6KOH + KClO₃ → 3K₂MnO₄ + KCl + 3H₂O
The filtrate is treated with carbon dioxide followed by chlorine. By this potassium manganate is converted into potassium permanganate.
3K₂MnO₄ + 2 CO₂ → 2KMnO₄ + MnO₂ + 2K₂CO₃
2K₂MnO₄ + Cl_{2 →} 2KMnO₄ + 2KCl

Potassium permanganate can also be prepared by electrically, by electrolysing warm solution of the manganate.
2K₂MnO₄ + 2 H₂O → 2KMnO₄ + H₂  + 2KOH

Physical Properties

It occurs in the form of deep, dark purple, monoclinic prismatic crystals and moderately soluble in water. The taste is sweet and astringent.

Chemical Properties

It is very powerful oxidizing agent both in dry state and in solution. Explosions may occur when it comes in contact with organic or other readily oxidisable materials.
It act as an oxidizing agent because it produces nascent oxygen in solution.

2KMnO4 + 3H₂SO4 → K₂SO₄ + 2MnSO₄ + 3H₂O + 5(O) (acid solution)
2KMnO₄ + H₂O → 2MnO₂ + 2KOH + 3(O) (Alkaline (or) neutral solution)

Potassium permangante oxidizes iodides, bromides, chlorides, ferrous salts, nitrites, sulphites, thio sulphates peroxides and oxalates. Organic materials such as ethyl alcohol and charcoal are readily oxidized.

Assay

It is assayed by titrating it with N/10 oxalic acid in presence of disulphuric acid at 70^oC. If the temperature is not maintained at 70C, the reaction will become slow.

5 (HOOC-COOH)+5(O) → 10CO₂ + 5H₂O

Storage:

It should be stored in well closed container.

Use

1. It is used as local anti infective.
2. It is used as mouthwash and gargle (more than 1 in 1000 solution).
3. It is also used as stomach wash in the treatment of Narcotic drug poisoning.

Protein Precipitant

SILVER NITRATE (AgNO₃)

Preparation

It is prepared by action of dilute nitric acid on pure silver. 3 parts of silver are added to the solution of 25% nitric acid (10 parts) and warmed. Then it is heated to expel the nitrous fumes, filtered and evaporated until it is dry.

3 Ag + 4 HNO₃ → 3 Ag NO₃ + NO + 2H₂O

Properties

It occurs as colourless crystalline compound odourless, bitter in taste. When it is exposed to light or organic matter it turns grey or greyish black. It is more soluble in water and in alcohol.
When it is heated, it melts at 212^oC to yellowish liquid and when heated further it decomposes in to metallic silver with evolution of NO₂ and O_2.
2AgNO₃ 2Ag + 2NO₂  + O₂

It gives white yellow-white precipitate with hydrochloric acid and other halogen salts.

Silver Mirror Test

Ammonium hydroxide with silver nitrate forms silver-ammonium complex. To this solution, if reducing agent like glucose is added the silver ions are reduced to metallic silver and silver mirror is formed.

Incompatibilities

It is incompatible with reducing agents, tartrates, sugars and tannins. In neutral and alkaline conditions precipitation results with halides, borax, hydroxide, phosphate sulphate etc.

Assay

It is estimated by dissolving in water, nitric acid is added to it and titrated against standard ammonium thiocyanate using ferric alum as indicator. The end point is the formation of reddish-brown colour.
AgNO₃ + NH₄ SCN → AgSCN  + NH₄ NO₃

Storage

It is decomposed (reduction) by light so it should be stored in well closed, glass container and protected from light.

Uses

1. It is used as antibacterial (0.01 – 0.5%).
2. At higher concentration it is used as Astringent (1% and above).
3. At very low concentration acts as bacteriostatic (0.0025 to 0.0050%).
4. Silver nitrate ophthalmic solution in 1% strength is used as eye wash.

MILD SILVER PROTEIN

It is a preparation with silver available in colloidal form by the presence of proteins or in combination with it. It contains not less than 19% and not more than 23.0% of silver.

Preparation

It is prepared by using silver salt with an excess of denatured protein (serum albumin, casein, or gelatin). The product is dried in vacuum and stored in amber coloured bottles.

Properties

It is a dark brown – blackish shining scales or granules, odourless and is hygroscopic, it is soluble in water but insoluble in alcohol, ether and chloroform.

Assay:

Same as that of silver nitrate.

Storage

It is stored in tightly closed amber-coloured glass containers, in dry and dark place. Disodium edetate (EDTA) in 10 mg/ml is used as stabilizer for aqueous solution.

Uses

1. Aqueous solution of 1-2% are used as antibacterial.
2. For rhinitis, tonsilities it is used in 0.5 – 10% of concentration.
   Only freshly prepared solutions are to be used. Since it has less free silver ions, it is effective antimicrobial and show less irritation and astringent effect.

Mercury Compounds

YELLOW MERCURIC OXIDE (HgO)

Preparation

It is prepared by pouring concentrated solution of mercuric chloride into a dilute solution of sodium hydroxide with constant agitation. This is then allowed to stand at room temperature for about an hour. Then the supernated liquid is decanted off and the precipitate is washed with water until the washings are free from alkali. The yellow precipitate is collected and dried on absorbent paper at 30C. The above steps are carried out in dark place to get bright orange-yellow product.
HgCl₂ + 2NaOH → Hg (OH)₂ + 2NaCl
Hg(OH)₂ → HgO + H₂O

Properties

It is an orange-yellow heavy amorphous powder, odourless and gets decolourized on exposure to light. It is practically insoluble in water and alcohol but readily soluble in dilute hydrochloric acid and dilute nitric acid.

On heating to red hot it decomposes into oxygen and vapour of metallic mercury.
2HgO → O_2 + 2 Hg

Assay

It is estimated by volumetric thiocyanate method. An accurately weighed quantity is dissolved in nitric acid and water. The solution is titrated against ammonium thiocyanate solution using ferric ammonium sulphate as an indicator.

Storage

It should be stored in tightly closed containers and protected from light.

Uses

1. It is used as mild antiseptic.
2. It is used as 1% solution for ophthalmic purpose to treat inflammation and
   conjunctivitis.

AMMONIATED MERCURY (NH₂ (Hg) Cl)

Preparation

It is prepared by adding 5% mercuric chloride solution to a mixture of 4 parts of dilute ammonia and 20 parts of water with constant stirring. The precipitate is collected, washed with cold water and dried below 30.
HgCl₂ + NH₃ → Hg (NH₂ )Cl+ NH₄Cl

Properties

It is white amorphous powder and is odourless, darkens on exposure to light. It is practically insoluble in water alcohol and ether.

Assay

It is treated with potassium iodide solution with stirring. The mercuric iodide formed in the reaction is converted into potassium mercuric iodide (K2HgI4) by potassium iodide. The liberated (alkali) ammonia and potassium hydroxide is titrated with hydrochloric acid using methyl orange as an indicator.

NH₂ HgCl + 2KI + H₂O → HgI₂ + NH₃ + KOH + KCl
HgI₂ + 2KI → K₂HgI₄

Uses

1. It is acting as mild antiseptic.
2. It is used in various skin infections caused by fungi, lice and other infestation.
3. It is used as an ointment and dusting powder in the strength of 5%.

Pharmaceutical Preparations of Mercuric Compound

1. Mercuric oxide eye ointment–
   Preparation contains 0.9 to 1.1% of HgO in simple ointment.
   Ointment is used to reduce inflammation and as antiseptic in conjuctivitis.
2. Ammoniated mercuric ointment–
   It contains 2.25 to 2.75% of NH₂ HgCl. The preparation is used as mild antiseptics.

SULPHUR AND ITS COMPOUNDS

SUBLIMED SULPHUR

Symbol : S
Syn : Flowers of Sulphur

Preparation

It is prepared by heating any kind of sulphur and condensing the vapour.

Properties

1. Fine crystalline powder.
2. It has faint characteristic odour but tasteless.
3. It is insoluble in water.

Use :
Antiseptic and scabicide.

PRECIPITATED SULPHUR

Symbol : S

Preparation (Small Scale)

It is prepared by acidifying sodium thiosulphate solution with hydrochloric acid. The unstable thiosulphuric acid is liberated, gets rapidly decomposed to give precipitated sulphur.
Na₂ S₂O₃ + 2 HCl → H₂S₂O₃ + 2 NaCl
H₂S₂O₃ → S + SO₂ + H₂O

Industrial Method

It is prepared by heating together sublimed sulphur and milk of lime for an hour.
2Ca(OH)₂ + 12S → 2 CaS₅ (cal. Penta sulphide)+ CaS₂O

CaS₅ (Calciumpenta Sulphide)+ 2 HCl → CaCl₂ + H₂S + 4S

Properties

1. Pale greenish yellow soft powder.
2. Odourless and tasteless.
3. Upon heating it burns with a blue flame.
   S + O2 =SO₂
4. It is insoluble in water and alcohol.

Use:

1. Good scabicide.
2. Antiseptic
3. Used in treatment of acne.
4. Parasiticide.

SELENIUM SULPHIDE

M.F. SeS₂

Preparation

It is prepared by passing hydrogen sulphide gas into selenious acid. The precipitate is filtered and dried.
H₂SeO3 (Selenious acid) + 2H₂S → SeS₂  + 5H₂O

Properties

1. It is orange powder having faint sulphide odour.
2. Insoluble in water, alcohol and organic solvents.
3. It dissolves in nitric acid and form selenious and sulphuric acid.
   SeS₂ + 16 HNO₃→ H2SeO₃ + 2H₂SO₄ + 16NO₂  + 5H₂O

Use: Anti dandruff