1

DOUBLE BLIND CONTROLLED DOUBLE BLIND CONTROLLED CLINICAL STUDIES OF A UNANI CLINICAL STUDIES OF A UNANI

HERBO-MINERAL CREAM IN PATIENTS HERBO-MINERAL CREAM IN PATIENTS OF PSORIASISOF PSORIASIS

Latif A. , Saleem A., Rahman S. Z. , & Latif A. , Saleem A., Rahman S. Z. , & Tahseen M. *Tahseen M. *

Department of Ilmul Advia, A. K. Tibbiya Department of Ilmul Advia, A. K. Tibbiya CollegeCollege

Aligarh Muslim University Aligarh. * Aligarh Muslim University Aligarh. * Department of Dermatology, J. N. Department of Dermatology, J. N. Medical College, A. M. U. Aligarh.Medical College, A. M. U. Aligarh.

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INTRODUCTIONINTRODUCTIONPsoriasis is a chronic remitting and relapsing scaly, Psoriasis is a chronic remitting and relapsing scaly, inflammatory and common skin disorder which is inflammatory and common skin disorder which is being treated by Unani System of Medicine ( a being treated by Unani System of Medicine ( a recognised traditional system by WHO ) from a recognised traditional system by WHO ) from a very long time*. Sources of Unani drugs for very long time*. Sources of Unani drugs for Psoriasis are herbs, animals & minerals.Psoriasis are herbs, animals & minerals.The present study, double - blind placebo The present study, double - blind placebo controlled, is done by using herbo-mineral controlled, is done by using herbo-mineral preparation as topical application in cases of preparation as topical application in cases of Psoriasis.Psoriasis.________________________________________________________________________________________________________________________* Kitabul- Hashaish of Dioscarides ( 70th B. C.)* Kitabul- Hashaish of Dioscarides ( 70th B. C.)* Jameal- Mufradat-al-advia wa alaghzia of Ibn Baitar. (1248 A. D. )* Jameal- Mufradat-al-advia wa alaghzia of Ibn Baitar. (1248 A. D. )* Al-Qanoon-fial-tibb (Cannon of Medicine) of Avicenna (980 - 1037 A. D.)* Al-Qanoon-fial-tibb (Cannon of Medicine) of Avicenna (980 - 1037 A. D.)* Al- Hawi of Mohammad b. Zakaria al-Razi (866- 925 A. D.)* Al- Hawi of Mohammad b. Zakaria al-Razi (866- 925 A. D.)

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Material & MethodsMaterial & MethodsDrugs:Drugs:

The formulation of Cream consists of the The formulation of Cream consists of the following ingredients:-following ingredients:-

1- Calomel (Hgcl- RasKapoor) 1- Calomel (Hgcl- RasKapoor) 5% 5% w/ww/w2- Camphor (2- Camphor (Cinnamomum camphora Cinnamomum camphora LinnLinn.. ) )

5% w/w5% w/w3- Litharge (Pbo- Murdarsang) 3- Litharge (Pbo- Murdarsang) 12% 12% w/ww/w4- 4- Psoralea corylifoliaPsoralea corylifolia Linn. oil Linn. oil 10% 10% w/ww/w5- Cream base 5- Cream base SQSQ

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Material and Method (Contd.)Material and Method (Contd.)STUDY PROTOCOLSTUDY PROTOCOL

((A) - Phsico-chemical studies: - Solubility, Smooth flow Test, pH, M. p., Absorption of A) - Phsico-chemical studies: - Solubility, Smooth flow Test, pH, M. p., Absorption of Cream by filter paper method & Tared Blade method:Cream by filter paper method & Tared Blade method:

(B) PATCH TEST (B) PATCH TEST (C) - Clinical Studies: - three groups of 25 patients of Psoriasis (Total numbers of (C) - Clinical Studies: - three groups of 25 patients of Psoriasis (Total numbers of Patients 75) of either sex and Patients 75) of either sex and different age groups were made as follows:different age groups were made as follows:(I) Test Drugs (I) Test Drugs (Herbo-mineral cream)(Herbo-mineral cream)

(II) Standard Drug (II) Standard Drug (Dithranol ointment)(Dithranol ointment)

(III) Placebo-(III) Placebo-(Pet Jelly)(Pet Jelly)

(D) Mode of Administration of Cream: Topical Application of Cream followed by (D) Mode of Administration of Cream: Topical Application of Cream followed by exposure to sunlight for 5 minutes in morning & eveningexposure to sunlight for 5 minutes in morning & evening

(E) Routine investigation and "Candle Grease" examination is made by scrapping of (E) Routine investigation and "Candle Grease" examination is made by scrapping of affected part of the skin. affected part of the skin.

(F) Evaluation of Cases after every 15 days up to 90 Days & Post treatment Followup (F) Evaluation of Cases after every 15 days up to 90 Days & Post treatment Followup is also done.is also done.

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Physico- Chemical Studies:Physico- Chemical Studies:General CharacteristicsGeneral Characteristics

SolubilitySolubility pHpH M. P.M. P. Smooth Smooth Flow TestFlow Test

ColourColour

(a) (a) Soluble in Soluble in chloroforchloroform & CCl4m & CCl4

b) b) Partially Partially Soluble in Soluble in Hot WaterHot Water

c)InSolublc)InSoluble in e in Alcohol, Alcohol, Water Water (Cold), (Cold), Pet-ether Pet-ether & ether& ether

Range-Range-6. 6- 6. 8 6. 6- 6. 8 (By Elico (By Elico pH pH Meter)Meter)IndicateIndicated d slightly slightly acidicacidic

Range Range fromfrom83 83 00C- 86 C- 86 00CC

By By ReichertReichertThermovarThermovarInstrumenInstrumentt

Uniform Uniform & Smooth & Smooth DistributiDistributionon

Blackish Blackish BrownBrown

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Drug absorption

0255075

100125150175

0 5 10 15 20 25 30 35 40

Time (Minute) Time Absorption Curve

(By Filter Paper Method)

Dru

g A

bsor

ptio

n

Drug absorption

7

Absorption Drug

0255075

100125150175

0 5 10 15 20 25 30 35 40Time (Minutes)

Drug

Abs

orpt

ion

AbsorptionDrug

Time Absorption Curve (By Tared Razor Blade)

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PATCH TEST OF HM-CREAM ON NORMAL PATCH TEST OF HM-CREAM ON NORMAL HUMAN SKIN OF FOREARMHUMAN SKIN OF FOREARM

S.No.S.No. SexSex

M M FF

IrritatiIrritationon

RednesRednesss(Rashes(Rashes))

HyperpigmentatHyperpigmentationion

BlisterBlister

112233445566778899

1010

MM

MMMM

MMMM

FF

FF

F F

F F FF

--------------------

----------

MildMild--------

--Light BlackishLight Blackish

--Light BlackishLight BlackishLight BlackishLight BlackishLight BlackishLight BlackishLight BlackishLight BlackishLight BlackishLight BlackishLight BlackishLight BlackishLight BlackishLight Blackish

--------------------

10%10% 80%80%

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PATCH TEST OF DITHRANOL ON NORMAL HUMAN PATCH TEST OF DITHRANOL ON NORMAL HUMAN SKIN OF FOREARMSKIN OF FOREARM

S.No.S.No. Age Age YearsYears

SexSex IrritatiIrritationon

RashesRashes HyperpigmentatioHyperpigmentationn

BlistersBlisters

1122334455667788991010

2828252515150606101028282020242417172121

M M FF

MM FFMMMM F F F F M MMM F F F F

++--++--++++----++--

MildMild----

MildMild----

MildMildMildMildMildMildMildMild

BlackishBlackishBlackishBlackish

Dark Blackish Dark Blackish Dark BlackishDark BlackishLight BlackishLight BlackishDark BlackishDark Blackish

BlackishBlackishBlackishBlackish

Light BlackishLight BlackishLight BlackishLight Blackish

----++++--++----++++

50 %50 % 60%60% 80%80% 70 %70 %

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CLINICAL STUDIESCLINICAL STUDIES

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Before Treatment

Cured (30 Days)

Cured (90 Days)

Before Treatment

1

2

12

3

4

Before Treatment

Cured (45 Days)

Cured (65 Days)

Before Treatment

13

Before Treatment

Cured (40 Days)

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A COMPARATIVE STATEMENT SHOWING TOTAL A COMPARATIVE STATEMENT SHOWING TOTAL RESPONSE OF THREE GROUPSRESPONSE OF THREE GROUPS

GroupGroupss

Compound Compound NameName

Total Total TherapeTherape

utic utic ResponsRespons

ee(a+b+c)(a+b+c)

CureCuredd

aa

RelivReliveded

bb

Partially Partially RelivedRelived

cc

No No ResponsRespons

ee

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22

33

HM Cream HM Cream (Test)(Test)

Dithranol Dithranol (Standard)(Standard)

PlaceboPlacebo(Pet- Jelly)(Pet- Jelly)

92 %92 %

88 %88 %

32 %32 %

68 %68 %

60 %60 %

NilNil

12 %12 %

16 %16 %

NilNil

12 %12 %

12 %12 %

32 %32 %

8 %8 %

12 %12 %

68 %68 %

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TOTAL RESPONSE OF HM CREAM, DIATHRANOL & TOTAL RESPONSE OF HM CREAM, DIATHRANOL & PET JELLYPET JELLY

0102030405060708090

100

HMCREAM

DITH. OINT.

PETJELLY

TOTAL RESPONSE

CURED

RELEIVED

PARTIALLYRELIVEDNO RESPONSE

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A COMPARATIVE STATEMENT SHOWING A COMPARATIVE STATEMENT SHOWING SIDE EFFECTS IN TEST & STANDARD SIDE EFFECTS IN TEST & STANDARD

GROUPSGROUPS

GroupsGroups Irritation (%)Irritation (%) Redness (%)Redness (%) Hyperpigmentation Hyperpigmentation (%)(%)

Blister Blister (%)(%)

TestTest MildMild ModeraModeratete

SeveSeverere

MilMildd

ModeraModeratete

SeveSeverere

Light Light BlackishBlackish

Dark Dark BlackishBlackish

66

(24.(24.6 )6 )

NilNil NilNil 2 2 (8)(8)

NilNil NilNil 1717

(68 )(68 )

NilNil NilNil

StandaStandardrd NilNil 55

(20)(20)

NilNil NilNil NilNil 77

(28) (28)

NilNil 10 10

(40)(40)

33

(12)(12)

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S. S. NoNo

Period Period of of

Relapse Relapse after after CuredCured

ChronicitChronicityy

AgeAge sexsex Site of Site of RecurrenceRecurrence

No. of RelapseNo. of Relapse

11

22

33

44

55

66

77

3 3 MonthsMonths

5 5 MonthsMonths

3 3 MonthsMonths

2 2 MonthsMonths

4 4 MonthsMonths

7 7 MonthsMonths

9 9 MonthsMonths

1-2 Yrs1-2 Yrs

2-5 Yrs2-5 Yrs

5-12 Yrs.5-12 Yrs.

12-24 12-24 Yrs.Yrs.

2-5 Yrs.2-5 Yrs.

5-12 Yrs.5-12 Yrs.

10-12 10-12 YrsYrs..

12 12 Yrs.Yrs.

31 31 Yrs.Yrs.

45 45 Yrs.Yrs.

47 47 Yrs.Yrs.

28 28 Yrs.Yrs.

35 35 Yrs.Yrs.

45 45 Yrs.Yrs.

MaleMale

MaleMale

FemaFemalele

FemaFemalele

MaleMale

FemaFemalele

MaleMale

Abd, legAbd, leg

Neck, ScalpNeck, Scalp

Neck, ScalpNeck, Scalp

BacksideBackside

ChestChest

Forearm & LegForearm & Leg

Scalp, Leg & Scalp, Leg & ArmArm

WholeWhole

Scalp OneScalp One

WholeWhole

WholeWhole

WholeWhole

WholeWhole

WholeWhole

RECURRANCE STATUS OF STANDARD GROUP (Dithranol RECURRANCE STATUS OF STANDARD GROUP (Dithranol Ointment)Ointment)

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RECURRANCE STATUS OF TEST GROUPRECURRANCE STATUS OF TEST GROUP (Herbo-mineral Cream)(Herbo-mineral Cream)

S. S. NoNo

Period Period of of

Relapse Relapse after after CuredCured

ChronicityChronicity AgeAge sexsex Site of Site of RecurrenceRecurrence

No. of RelapseNo. of Relapse

11

22

33

44

55

6 6 MonthsMonths

8 8 MonthsMonths

8 8 MonthsMonths

11 11 MonthsMonths

12 12 MonthsMonths

1-2 Yrs1-2 Yrs

2-5 Yrs2-5 Yrs

5-12 Yrs.5-12 Yrs.

12-24 Yrs.12-24 Yrs.

10-12 Yrs.10-12 Yrs.

8 Yrs.8 Yrs.

35 35 Yrs.Yrs.

38 38 Yrs.Yrs.

45 45 Yrs.Yrs.

50 50 Yrs.Yrs.

FemalFemalee

MaleMale

MaleMale

FemalFemalee

MaleMale

ScalpScalp

LegLeg

ForearmForearm

LegLeg

LegLeg

WholeWhole

Scalp OneScalp One

WholeWhole

WholeWhole

WholeWhole

No. Cases 5 (20 %)No. Cases 5 (20 %)

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The test drug (containing Litharge) is described as The test drug (containing Litharge) is described as anti-inflammatory and has a quality of potentiating anti-inflammatory and has a quality of potentiating drug when applied topically (Ghani, 1921). During our drug when applied topically (Ghani, 1921). During our study we also found that the test drug is beneficial in study we also found that the test drug is beneficial in psoriasis total therapeutic response- 92% and has more psoriasis total therapeutic response- 92% and has more absorption capacity in comparison to normal skin .As absorption capacity in comparison to normal skin .As mentioned in classical literature that the drug is safe, mentioned in classical literature that the drug is safe, we could also found less adverse effects with test drug we could also found less adverse effects with test drug in comparison to dithranol. The recurrence rate of in comparison to dithranol. The recurrence rate of psoriasis with dithranol is 28% while observed less psoriasis with dithranol is 28% while observed less number side effects with test drug (i. e., 20%) also number side effects with test drug (i. e., 20%) also shows the better option of drug therapy with test drug. shows the better option of drug therapy with test drug. The above favouring remarks clearly shows that the The above favouring remarks clearly shows that the drug is effective when applied topically. The drug seems drug is effective when applied topically. The drug seems to decrease proliferation of keratinocytes. The to decrease proliferation of keratinocytes. The mechanism by which the test drug causes inhibitory mechanism by which the test drug causes inhibitory effects on Keratinocyts proliferation are not effects on Keratinocyts proliferation are not understood, and needs further clarification.understood, and needs further clarification.

DISCUSSIONDISCUSSION

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CONCLUSIONCONCLUSION It is concluded that topical It is concluded that topical

application of this Herbo- mineral application of this Herbo- mineral cream with phototherapy is having cream with phototherapy is having clinical significance in the treatment clinical significance in the treatment of Psoriasis with less side effects. of Psoriasis with less side effects.

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Drug absorption

0255075

100125150175

0 5 10 15 20 25 30 35 40

Time (Minute) Time Absorption Curve

(By Filter Paper Method)

Dru

g A

bsor

ptio

n

Drug absorption

22

Absorption Drug

0255075

100125150175

0 5 10 15 20 25 30 35 40Time (Minutes)

Drug

Abs

orpt

ion

AbsorptionDrug

Time Absorption Curve (By Tared Razor Blade)