Antimicrobial and astringent agents - Pharmaceutical Inorganic Chemistry B. Pharma 1st Semester

Antimicrobial and astringent agents

Antimicrobial agents: These are the chemicals or its preparation that help in reducing or preventing infection due to microbes. There are several terms used in describing anti-microbial activity. First let’s study the definition of these terms.

Antiseptic: These are the agents or substances that are able to kill or prevent the growth of microorganisms that is fungi, bacteria, etc. They widely applied on the living tissues. They act by inhibiting the growth of microbial multiplication and metabolic activities or by killing the microorganisms. An ideal antiseptic kills the microorganism without causing any damage to the host. They can be applied to all parts of the body and used in the form of mouthwashes, soaps, deodorants, nasal spray, etc.

Disinfectants: These are the agents or substance that prevents infection by the destruction of pathogenic microorganisms. They are usually applied to the non-living things like for the sterlisation of surgical equipment. It is helpful in maintaining the public places like sanitation or even in hospital etc. Some chemical disinfectants are too irritant and corrosive to the skin or tissue, so it not used on the living tissue.

Germicide: These are substances that kill the microbes. This is further used more specifically for different types of microbes like, bactericide for bacteria, fungicide for fungus, virucide for virus, etc.

Those agents which do not kill the microbes but just inhibit the growth of microorganisms are described by terms using the suffix stat for examples like bacteriostat, fungistat, etc., as the Greek word static's means 'standing still'.

The term's antiseptic and germicide may be further specified according to their area and type of use as topically or internally. Internal agents are those absorbed systemic and that not absorbed internally that is nonsystematic.

An antimicrobial agent should have the following properties.

1. It should posse antiseptic or germicide activity and not bacteriostatic activity.

2. It should have rapid onset of action and sustained activity.

3. It should show good activity whatever might be the concentration of agent used.

4. It should not cause local cellular damage or should not interfere with body defenses.

5. It should not show any systemic toxicity from topical application.

6. It should have broad spectrum of activity against bacteria, fungi, protozoa, etc.

7. The topical antimicrobial agent should have favorable lipid water distribution coefficient so that its effectiveness has been best.

Mechanism of action:

The Mechanism of action of these agents may range from mild astringent to powerful oxidative processes. Inorganic compounds are generally not used internally but for topical application like oral, skin infection, etc.

Inorganic compounds generally exhibit antimicrobial action by involving either of the following three mechanism through,

1. Oxidation. 2. Halogenation. 3. Protein binding or precipitation.

These represent the primary chemical interactions or reactions that occur between microbial protein and agent and result in death or inhibition of growth of microbes.

Oxidation mechanism: Compounds acting by this mechanism belong to class of peroxide peroxyacids, oxygen liberating compounds like permanganate and certain oxo halogen anions. These anti-infective agents bring about oxidation of active functional groups present in proteins or enzymes, which are necessary for the growth, or survival of microorganisms and also which reducing in nature. These cause a change in the shape of the protein and there by alter its function.

For examples: A free sulfhydryl group has been essential for function of various proteins and enzymes. If this free sulfhydryl group is destroyed by oxidation into formation of di sulfide group, the microorganism will die because of the altered protein molecule.

Halogenation mechanism: Compounds that are able to liberate the chlorine or hypochlorite or iodine act by this mechanism. The category of agents act on the peptide linkage and alter its potential and property. The destruction of specific function of protein causes death of microorganisms.

Most of the enzymes are proteineous in nature. A protein molecule is composed of a variety of amino acids connected through a peptide linkage (-CONH-) if an hypo chlorites attaches the peptide linkage by replacing the H by Cl then protein molecule will have an altered structure and the microorganisms.

Amino acid-CONH- Amino acid     halogenation     Amino acid -COCl-Amino acid.

(Protein structure)                                                        (Altered structure)

Protein precipitation:  This type of mechanism involves the interaction of protein with metallic ions having large charge or radius ratio or strong electrostatic fields. Hence most of the metals belonging to groups IB, IIB, IIIA or transition metals show protective activity but alkali alkaline earth metals do not show this activity. The nature of interaction of metal with protein takes place through polar group of protein, which acts as ligand and metal ions as Lewis acid. The chelate formed may be strong chelate giving rise to inactivation of protein. This action in general non-specific and at sufficient concentration will react with host as well as with microbial protein. The protein precipitant properties of metal cations can be altered accordingly to the concentration at the site of action.

By increasing the concentration, antimicrobial, astringent, irritant and corrosive properties are available.

The various inorganic compounds studied under above mechanism are as follows:

Potassium permanganate, Boric acid, Hydrogen peroxide*, Chlorinated lime*, Iodine and its preparations

Hydrogen peroxide

Chemical formula: H2O2

Molecular weight: 34.0 g/mol

Standards: 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.

Method of Preparation:

1. It is obtained adding thick paste of barium or sodium peroxide in ice cold water to a calculated quantity of ice cold solution of sulphuric acid. The insoluble barium sulphate

Chemical reactions:

Na2O2 + H2SO4 → H2O2 + Na2SO4

2. By electrolysis of 50 percent ice cold sulphuric acid. First per disulphuric acid will be formed which on distillation under reduced pressure gives hydrogen per oxide. The yield of hydrogen peroxide is 30%. The distillate containing hydrogen per oxide is analysed and is adjusted to the required strength.

Chemical reactions:

2H2SO4 → H2S2O8

H2S2O8 + 2H2O → 2H2SO4 + H2O2

Description:

• A clear, colourless liquid; odourless

• It decomposes in contact with oxidisable organic matter and with certain metals and also if allowed to become alkaline

Assay Principle: REDOX TITRATION PERMANGANOMETRIC TITRATION.

The assay method is based on the oxidation-reduction that is redox titration; the assay is based on the reducing property of the hydrogen per oxide. Simultaneous oxidation and reduction takes place between hydrogen peroxide and potassium permangate, in presence of the acidic media, which is maintained by sulphuric acid, the hydrogen per oxide is oxisidised to oxygen and permanganate ion is reduced to manganese ion. In this titration potassium permanganate acts as self-indicator, the end point is appearance of permanent pale pink

Chemical reactions:

2KMnO4 + 3 H2SO4 + 5H2O2 → K2SO4 + MnSO4 + 5O2 + 8H2O

Storage: Store protected from light in containers resistant to hydrogen peroxide at a temperature not exceeding 30°C. If the solution does not contain a stabilising agent, it should be stored in a refrigerator (2° to 8°C). It should not be stored for long periods

Medicinal uses:

     Anti-microbial agent

     Bleaching agent

     Antidote for phosphorus and cyanide poisoning

Iodine

Chemical formula: I2

Molecular weight: 253.8 g/mol

Standards: Iodine contains not less than 99.5 per cent and not more than 100.5 per cent of Iodine

Method of Preparation:

Iodine is obtained by natural source, by extracting kelp (seaweed’s ash) with water. The solution is concentrated to remove salts of sulphate and chloride leaving freely soluble sodium and potassium iodide in the mother liquor. To this solution sulphuric acid is added to remove sulphur and sulphides, which gets liberated, from small amount of thio sulphates and sulphide is allowed to settle down. The mother liquor is decanted and to this solution manganese di oxide is added and iodine distils over

Chemical reactions:

2NaI + 3H2SO4 + MnO→ MnSO4 + 2NaHSO4 + I2 + 2H2O Description:

     Heavy, bluish-black, rhombic prism or plates having metallic lusture

     Peculiar odour

     Irritant

     It volatilises at ordinary temperature

     Freely soluble in chloroform and ether, soluble in water in presence of potassium iodide

Storage: Store in ground-glass-stoppered containers or in earthenware containers with waxed bungs.

Medicinal uses:

    Counter irritant

    Disinfectant

    Proper thyroid functioning

Preparations of Iodine

    Aqueous iodine solution

    Weak iodine solution

    Strong iodine solution

    Povidone-Iodine solution

Aqueous iodine solution

Synonym: Lugols solution

Standards: It is having 5%w/v of iodine and 10 % w/v of potassium iodide in purified water

Composition:

    Iodine --- 50g

    Potassium iodide --- 100g

    Purified water sufficient to produce-----1000 ml

Method of preparation: Potassium iodide and iodine are first of dissolved in 100 ml of water with trituration or shaking process. Then the volume is made upto 1000 ml with purified water.

Description

     Transparent

     Brown liquid,

     Having the smell of iodine

Storage condition: It is preserved in well closed container of glass or plastic which are resistant to iodine. It is not stored in metallic containers because iodine attacks metal.

Medicinal uses:

     Good source of iodine (internally)

     Externally as germicide, fungicide

Advantages:

     Non irritant

Weak iodine solution

Synonym: Iodine tincture or tincture of iodine

Standards: It is having 2%w/v of iodine and 2.5 % w/v of potassium iodide in 50 % alcohol

Composition:

     Iodine --- 20g

     Potassium iodide --- 25g

     Alcohol (50%) to produce-----1000 ml

Method of Preparation: Potassium iodide and iodine are first of dissolved in 100 ml of 50 % alcohol. Then the volume is made upto 1000 ml with 50 % alcohol

Description:

     Transparent

     Brown liquid,

     Having the smell of iodine

Storage condition: It is preserved in well closed container of glass or plastic which are resistant to iodine. It is not stored in metallic containers because iodine attacks metal.

Medicinal uses:

     Good source of iodine (internally)

     Externally as germicide, fungicide

     Well known antiseptic

Disadvantages:

      Irritant

Strong iodine solution

Standards: It is having 10 %w/v of iodine and 6 % w/v of potassium iodide in 90 % alcohol

Composition:

     Iodine --- 100g

     Potassium iodide --- 60g

     Purified water sufficient----100 ml

     Alcohol (90%) to produce-----1000 ml

Method of Preparation: Potassium iodide and iodine are first of dissolved in 100 ml purified water. Then the volume is made upto 1000 ml with 90 % alcohol

Description:

     Transparent

     Brown liquid,

     Having the smell of iodine

Storage condition: It is preserved in well closed container of glass or plastic which are resistant to iodine. It is not stored in metallic containers because iodine attacks metal.

Medicinal uses:

     Good source of iodine (internally)

     Externally as germicide, fungicide

     Well known antiseptic

Disadvantages:

     Irritant

Povidone –Iodine solution

It is an aqueous solution of Povidone iodine. It is complex produced by the interaction between iodine and Povidone (Poly vinyl pyrrolidine). The complex is having about 10 % of iodine.

Description:

     Yellowish brown, amorphous powder,

     Having a characteristic odour

     Soluble in water and alcohol

      The solution is transparent in nature and has reddish brown colour and faint smell of iodine

     Its aqueous solution is having acidic pH

Storage: It is kept in a closed container and remains stable. Medicinal uses:

     Bactericidal

     Disinfection of skin cuts and wounds and even applied on burnt cases also.

Advantages:

      Water solubility

      Nonirritant

      Less toxicity

      Non staining in nature

Potassium permanganate

Chemical formula: KMnO4

Molecular weight: 158.0g/mol

Standards: Potassium Permanganate contains not less than 99.0 per cent and not more than 100.5 per cent of KMnO4

Method of Preparation: On large scale potassium permanganate is prepared by mixing a solution of potassium hydroxide with manganese di oxide and potassium chlorate. The mixture is boiled, evaporated to yield the residue which is heated in iron pans until it has acquired a paste consistency.

Chemical reactions:

3MnO2 + KOH + KClO3 →K2MnO4 + 3H2O+ KCl

Potassium manganate (green) so formed is extracted with boiling water and a current of chlorine or carbon di oxide or ozonised air is passed in to the liquid until it gets converted to permanganate. The manganese di oxide so formed is removed continuously so as to prevent its breaking down to manganate.

Chemical reactions:

6K2MnO4 + 3Cl2 → 6 KMnO4 + 6KCl

The solution of potassium permanganate is drawn off from any precipitate of manganese di oxide which is then concentrated and crystallised. The crystals are then centrifuged and dried.

Description:

     A dark purple or brownish black, granular powder or dark purple or almost black slender, prismatic crystals

     Having a metallic lustre

     Odourless.

     It decomposes on contact with certain organic substances

Storage: Store protected from moisture

Medicinal uses:

    Anti-microbial agent

    Antiseptic in mouth wash

    Anti-dote: Barbiturates, chloral hydrate

    Veterinary practice: antiseptic

Chlorinated lime

Chemical formula: Ca(OCl) Cl

Molecular weight: 142.9 8g/mol

Standards: It contains not less than 30 per cent w/w of chlorine

Synonym: Calcium hypochlorite, Calcium oxychloride, Bleaching powder

Method of preparation: By action of chlorine gas on calcium hydroxide. Calcium hydroxide is spread on the shelves in a suitable container, then the chlorine gas is introduced at the top of the chamber and then allowed to pass through the contents of the shelves. This step is carried out at 25oC, thereby minimising the formation of calcium chloride, when absorption of chlorine gas gets completed, powdered lime is blown into the chamber to absorb the excess of calcium chlorate.

Chemical reaction:

Ca (OH)2 + Cl2 → Ca(OCl) Cl  + H2O

Description

It occurs as a dull white powder having a charteristic odour. When exposed to air, gradually absorbs moisture and gradually gets decomposed. Slightly soluble in water and alcohol

Assay: Principle: Based on Redox titration, Iodometric titration

The available chlorine in the compound is liberated by the action of acetic acid, then an equivalent weight of chlorine gas is replaced with iodine by the action of potassium iodide. The liberated iodine is then titrated against sodium thio sulphate using starch as mucilage. Until the blue colour changes to colourless

Chemical reactions:

Ca (OCl)Cl + 2CH3COOH →(CH3COOO)2Ca + Cl2 + H2O Cl2+ 2KI→ I2+ 2KCl

I2+ 2Na2S2O3 → 2NaI + Na2S4O6

Storage: Store in well closed container in a cool place

Medicinal Uses:

    Disinfectant

    Bleaching agent

Boric acid

Chemical formula: H3BO3

Molecular weight: 61.8

Standards: Boric Acid contains not less than 99.5 per cent and not more than 100.5 per cent of H3BO3, calculated on the dried basis

Synonyms: Borarcic acid, ortho boric acid

Method of preparation: Boric acid may be prepared by reacting borax (sodium tetra borate deca hydrate) with a mineral acid, such as Sulphuric acid

Na2B4O7 +H2SO4 + 5H2O → Na2SO4 + 4H3BO3

Description:

     A white, crystalline powder or colourless shiny plates unctuous to the touch or white crystals

    Odourless

    Slightly acidic and bitter in taste

    Stable in air

    Weak acid pKa=9.19

Storage: Store protected from moisture

Medicinal uses:

    Anti-microbial agent: weak germicide

   Local anti-infective

    Aqueous solution: eye wash and mouth wash

    Dusting powder

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