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					AN INSIGHT ON RESEARCH AND DEVELOPMENT IN
       CCRAS WITH SPECIAL FOCUS ON
     DEVELOPMENT OF AYUSH QOL -2 FOR
IMPROVEMENT OF QUALITY OF LIFE (QOL)IN HIV /
                   AIDS




                                Dr. G.S.LAVEKAR
                                      DIRECTOR
                                          CCRAS
Initiation of Science
 SCIENTIFIC METHODOLOGY OF LEARNING, CLINICAL PRACTICE AND
 RESEARCH IN AYURVEDA

 •The process of learning, research and clinical practice are scientific and
 evidence based. Like other systems of ancient Indian learning, Ayurveda is
 discovered through most suitable sources (Paramanas) viz.
  (1) Pratyaksha (direct perception),
  (2) Anumana (logical inference),
  (3) Aptopadesa (verbal and authentic
      documentary testimony),
  (4) Yukti (experimental evidence) etc. which are
       reproducible
 •To revitalize these basic concepts, it is pivotal to create the measurable
 objective evidences with the aid of modern science and technology.
 •This would help for sustainable utilization of maximum diagnostic and
 therapeutic principles of these systems and create evidences which are
 reproducible.
Emphasis Of Ayurveda On Integration – A Key issue

•Understands mind-body & spirit connection, believes in
body’s self healing power, involves the patients in decision
making, reassures about positive aspects, sets himself as a
role model, is honest, truthful dedicated and committed and
is willing to accept integrated system of medical practice.

•Ayurveda emphasizes to adopt knowledge of various
sciences.
•Through studying any single branch of science, a physician or
surgeon never get the complete knowledge of Medical Science.
•Therefore he should study as many allied branches of science or
philosophy as possible.
•Authors of Ayurvedic texts emphasized to study all the related
sciences which have implicating with the medicine i.e. Biology,
Chemistry etc.
•They clearly mentioned that one should use the additions of the
updated technology to enrich ones own system and use all the
tools & techniques of the scientific community to make their science
to go in pace with the present world.
Central Council for Research in Ayurveda and Siddha,




Established in 1978, after the bifurcation of erstwhile
CCRIMH (1969), is an Apex body in India for the
Formulation
• Co-ordination
• Development
• Promotion
of research in Ayurveda and Siddha Systems of
Medicine on scientific lines.
                                           CCRAS

Central Research institute     Regional Research institute          Research Units/Centres
                10                           16                               12

  Ayurveda           Siddha      Ayurveda           Siddha             Ayurveda         Siddha

New Delhi                        Patna            Pondicherry   Hastinapur        Palayamkottai [CRU]
                     Chennai
Patiala                          Junagarh
                                                                ALRCA        Palayamkottai [SMPU]
Cheruthuruthy                    Trivandrum
                                                                Kottakal             Chennai
Mumbai                          Tarikhet
                                                                  Jamnagar[MCR]
                                   Pune
Kolkata                                                          Jamnagar[DSRP]
                                 Hyderabad
Lucknow
                                 Itanagar
Gwalior                                                          Leh
                                 Guwahati
Jaipur                                                           Car-Nicobar[THCRP]
                                 Gangtok
Bhubneshwar
                                  Mandi                         Ahmedabad
                                  Jammu                          Bangalore
                                  Jhansi
                                  Nagpur
                                 Vijayawada                TOTAL:38
                                 Bangalore
                RESEARCH AREAS
           RESEARCH AREAS
1. Literary Research (Revival and retrieval of rare books
   and manuscripts)
2. Fundamental research (Anukta dravyas, Prakriti)
3. Drug research
4. Clinical Research
5. RCH Research
6. Neutraceutical Research (Antartica Tea and Antartica
   laddu, food supplement for school going children )
7. Cosmeceutical Research (AYUSH face pack)
8. Bio Medical Instrumentation Research ( Panchkarma
   instruments)
SIGNIFICANT LEADS
•    Ayush-64 for Malaria

•    Ayush-56 for epilepsy

•    Ayush-82 for Diabetes mellitus

•    777 Oil for Psoriasis

•    Antartica Tea and Antartica laddu

•    Ayush Face Pack

•   Anti-dandruff, Anti fungal & Anti-pollutant/Air
     refreshing agent
•   Pippalyadi Yoga an oral contraceptive for females.
DRUG RESEARCH
               (SURVEY ,CULTIVATION ,DRUG STANDARDIZATION ,
                     AND PHARMACOLOGICAL STUDIES)

No. of Raw drugs collected                         1767
No. of Plant Specimens Collected                   1,20,000
No. of Folk-Claims Collected                       3800
No. of the Gardens                                 6
     Area under cultivation (in acres)             165
     Total No. of species under cultivation        460
     No. of Guggulu plants under cultivation       15000
     No. of plants included in AFI – I             200
Pharmacological Studies: More than 340 drugs used in Ayurveda and Siddha including
single drugs, compound formulations and coded drugs have been investigated in vivo and
vitro experimental models for routine pharmacological screening as well as for specific
effects.
LITERARY RESEARCH
  -   Books and Monographs Published >90
  -   Journals of CCRAS:
       - Journal of Research in Ayurveda & Siddha
       - Bulletin of Medico-Ethno-Botanical Research
       - Bulletin of Indian Institute of History of Medicine
  -   News letter
  - The Council has published a Database on medicinal plants           used
  in Ayurveda ( In Seven Volumes)
  -   From    60      Libraries/Repositories/Museum        collected    994
      Manuscripts
   - Microfilms – 272
                NEW DRUG DEVELOPMENT
S.No.                    Area                                    Status
 1         Identification of priority areas and 30 coded drugs have been formulated
        formulation of coded drugs for new for different disease conditions based
        programme projection                    on national priority considering the
                                                strength of Ayurveda
 2       Literary    survey    and  formulation   Extensive literary documentation has
        Hypothetical basis on each formulation    been done on 30 coded drugs and got
        and approval of scientific advisory       the approval of SAC
        committee (SAC)
 3       Development of trial protocols for the   15 protocols on identified diseases
        identified conditions.                    conditions have been completed and
                                                  preparation for other protocols are in
                                                  progress.
 4      Pre-clinical standardisation and toxicity Eight formulations have completed.
        studies.
 5      Biological/ Targeted activities           One formulation completed and others
                                                  are in progress.
 6      Trial drug preparation
                                                  Preparation of eight formulations in
                                                  progress
CLINICAL TRIALS OF CODED FORMULATION (OF WHICH STANDARDIZATION,
SAFETY AND TOXICITY STUDIES BIOLOGICAL/TARGETED ACTIVITY STUDIES
ARE COMPLETED) ON SELECTED CLINICAL CONDITIONS.


1.  Ayush Rasayan-A and Ayush Rasayan-B for Improving QOL
    in elderly persons
2. Ayush-RP for Sickle Cell Anaemia
3. Ayush-Osto for Osteoporosis
4. Ayush-Osto for fractures
5. Ayush-LIV for Hepatitis B & C
6. Ayush-M for Migraine
7. Ayush-SL Capsules and Ayush-SL External application for
    Morbid cases of Filariasis
8. Ayush Manas for Mental retardation
9. Ayush QOL-2 A for improvement of quality of life in HIV/AIDS
10. Ayush QOL 2-C for improvement of quality of life in cancer
CLINICAL TRIALS OF SELECTED CODED FORMULATION (OF
WHICH    STANDARDIZATION, SAFETY AND TOXICITY STUDIES
BIOLOGICAL/TARGETED ACTIVITY STUDIES ARE IN PIPE LINE) ON
SELECTED CLINICAL CONDITIONS.

1.   Ayush-RCH-2 for Menopausal syndrome
2.   Ayush-CARD for Chronics stable Angina (Hridroga)
3.   Ayush-UT for Urolithiasis (Mutrashmari)
4.   Ayush-for DIAB Diabetes (Madhumeha)
5.   Ayush-RHU-2 and Erand Taila-oil of Ricinus
     communis for Rheumatoid Arthritis (Amavata).
6.   Ayush-RCH-1 and Ayush-RCH-3 for DUB(Animitta
     raktapradara)
7.   Ayush-BA for Tamaka Swasa
8.   Ayush-VJ-1and -Ayush-VJ-2 for Malaria (Vishama
     jwara)
        PROJECTS OF NATIONAL & GLOBAL
                 IMPORTANCE



   BIOMEDICAL                         RCH
INSTRUMENATION     RCH

                                      PIPPALIYADI YOGA

                                      JAMA DRUGS

   JAMA DRUGS      PIPPALIYADI YOGA   BIOMEDICAL
                                      INSTRUMENATION
    IPR PROTECTION AND COMMERCIALIZATION

1    Patents obtained                                19


2    Patents filed/processing for filing             12


3    Patents /Processes      released to the Industry 6
     /commercialized )
COLLABORATIVE RESEARCH
CCRAS Institutes   Collaborating Institutes   Research Area
CCRAS              Rashtrapathi Bhavan        Preparation of certain
Head Quarters      (RPB)                      Ayurvedic Medicine by
                                              using      the     Herbal
                                              resources of
                                              Rashtrapathi Bhavan and
                                              Fragrance      &    Flavor
                                              Development        Centre,
                                              Kannauj.(In progress)
CCRAS              NIN, Hyderabad.            To develop Nutritional
Head Quarters      &                          supplement for
                   AMUL, Gujarat              • School going Children
                                              •    Pregnant women
                                              •   Geriatric population
                                                   (In progress)
RRIA, Kothrud, Pune   Bhide foundation         1. Analytical study of
                      Pune                     Bhasmas (Rasmanikya)
                                               2. Project entitled,
                                               “Synthesis
                                               Characterization, toxicity
                                               studies and clinical trials
                                               of Bhasmas-a
                                               Comprehensive study” (In
                                               progress)
CCRAS, Hqrs.          University of Delhi      Genetic susceptibility to
                      National Institute of    rheumatoid arthritis using
                      immunology and Holy      a novel combination of
                      family Hospital, Delhi   prakriti   based    control
                                               selection & molecular
                                               analysis tools
CCRAS Hqrs /          CCMB (CSIR)              Clinical    evaluation   of
CRI, New Delhi        Hyderabad                AYUSH-CT        drops    in
                                               improving the quality of
                                               vision and visual acuity in
                                               age    related    immature
                                               cataract (In progress)
CCRAS Hqrs /     AIIMS Delhi Under process   Clinical Studies of AYUSH-
CRI, New Delhi                               CT in age related immature
                                             cataract (In progress,
                                             Ethical clearance awaited)



CCRAS Hqrs /     AIIMS Delhi Under process Clinical    Evaluation     of
CRI,New Delhi                              AYUSH-DE Drops in Dry
                                           Eye Syndrome (In progress,
                                           Ethical clearance awaited)
CCRAS Hqrs /     AIIMS Delhi Under process Clinical   Evaluation    of
CRI,New Delhi                              AYUSH-AC Drops in Simple
                                           Allergic Conjunctivitis (In
                                           progress, Ethical clearance
                                           awaited)

CCRAS Hqrs /     IIT, New Delhi              Atomization of
CRI,New Delhi                                Panchakarma Equipments
                                             Shirodhara & Kshara sutra-
                                             (in ogress) Sarvanga Dhara-
                                             (commercialization in
                                             progress)
Clinical Research Unit,   NIMHANS, Banglore      Autonomic functions tests in
Banglore                                         patients with depression
                                                 (vishada) Role of Ayurvedic
                                                 therapy ad transcranial
                                                 mangnetic stimulation.

                                                 Efficacy of Manasamitram
                                                 Vadakam on Generalized
                                                 Anxiety Disorder : A
                                                 polysomnographic Study –

                                                 Efficacy of Ayurvedic treatment
                                                 for motor weakness due to
                                                 ischemic stroke a prospective,
                                                 randomized, controlled study
Central Research          TATA Cancer Research   1. Improvement of quality of
Institute, Mumbai         Institute              life in Cancer patients (Study
                                                 will be initiated shortly)
                                                 2.Screening of Herbal drugs for
                                                 potential anti-Cancer activity
                                                 (in the process of finalization)
Central Research       Grant Medical College &   Improvement of quality of
Institute, Mumbai      J.J. Hospital, Mumbai     life in AIDS/HIV patients –
                                                 (in process)
CCRAS Hqs              M/S Nath Agricultural    Development of topical
                       foundation& Cold storage analgesic         & anti
                       company                  inflammatory agent from
                                                C. longa leaf oil
CRI, Siddha, Chennai   Dept. of Orthopedics,     Asthi             saushirya
                       kilpauk Medical college   (Osteoporosis)–        Pre-
                       Chennai                   clinical studies completed.


CRI, Siddha, Chennai   ANNA Peripheral Hospital Yakrit Vikar (Hepatitis – B)
                       attached to kilpauk      preclinical         studies
                       Medical college Chennai  completed

CRI, Siddha, Chennai   Women & Children          Rakta               Pradar
                       Hospital, Egmore,         (Dysfunctional      Uterine
                       Chennai                   Bleeding)–pre-clinical
                                                 studies completed
CCRAS Hqs. (Funded NIPER (CSIR), Mohali        Standardization, Shelf
by Dept. of Family                             Life, Stability, Biological
Welfare)                                       Activity , Bio Availability
                                               Studies, Estrogen
                                               Receptor Assay of
                                               Pippalyadi Yoga Capsule -
                                               A Female oral
                                               contraceptive - in
                                               progress.

CCRAS Hqs.          NIN,Hyderabad              Toxicity studies of five coded
                                               formulations for Urolithiasis,
                                               Menopausal syndrome, Cardiac
                                               Risk Factor, Rasayana for
                                               elderly person, Diabetes
                                               Mellitus- completed

CCRAS Hqs           Sports authority           Development of wound healing
                    of India Pharmacological   drugs for sports injury - under
                    Research Unit              process
                    CCRAS at GAU, Jamnagar
Development Of AYUSH QOL-2
Global Scenario


     •The Joint United Nations Program on HIV/AIDS and the World
     Health Organization (As per AIDS epidemic update, December
     2003-UNAIDS) estimated that 34-46 million people are living with
     HIV/AIDS.

     •More than 20 million have died from AIDS. 4 million children have
     been infected since the virus first appeared.

     •A report released by UNAIDS concludes that at the current rate
     of infection there would be 45 million new cases by 2010.
Indian scenario
•In India HIV/AIDS epidemic is about 20 years old and is considered to be the most
serious public health problem.

•The first HIV infection was reported from Chennai (Madras) and first AIDS case from
Mumbai (Bombay) in 1986.

• The infection has currently taken epidemic proportions in the country. NACO estimates
that 5.13 million persons are currently living with HIV in India by end of 2004.

• 28 thousand new infections were reported in 2004. Although there has been some
decline in the new HIV infections in 2004, yet the situation continues to be grim.

•The HIV, which has earlier confined to high risk categories, has started percolating
down to general population with 2% prevalence in Mumbai, >1%in Hyderabad,
Banglore, Chennai and <1% in Kolkata, Ahmedabad and Delhi. The national prevalence
percentage, however, is currently 0.91%.
Indian scenario

Indian states have been divided into 3 groups on the basis of the
prevalence of the disease in the population:
Group 1: States of Maharashtra, Tamil Nadu, Karnataka, Andhra
Pradesh, Manipur, Goa where HIV prevalence in general
population >5% and >1% in antenatal women.

Group 2: States of Gujarat, Pondicherry where HIV prevalence in
general population is >5% and in antenatal women <1%.

Group 3: Those states where HIV prevalence in general
population is <5% and in antenatal women is <1%.
Indian scenario

•Worst hit state is Andhra Pradesh with 2.25% of its
population estimated to be infected
• Rural and urban populations are equally
vulnerable, with 58.5% of those infected live in
village.

• 31.32lakh are male among the total number of
persons infected with HIV,
Introduction

        In spite of recent advances in the treatment of HIV/AIDS, there is
         no known cure: the final outcome for every HIV-infected patient
         is death

        A patient may die as a consequence of his/her first HIV
         manifestation or may develop a life-threatening OI and
         recover if appropriate treatment is given on time


        Most patients, however, will experience an increasing
         frequency of health problems and finally reach a stage of
         severe immunosuppression over a period of several years


        As the disease progresses, the need for symptomatic relief will
         become more important than curative treatment
      ROLE OF AYUSH

    The most prevalent users of Ayurveda /TSM are
    individuals who have incurable, non–life-threatening
    conditions that may be chronic.
   The second largest group of users are those
    struggling with chronic, potentially life-threatening
    diseases, such as cancer and HIV-AIDS.
    Both groups turn to Ayurveda /TSM for a variety of
    reasons, such as to improve immune functioning, to
    improve overall functioning, to increase quality of life,
    to cope with side effects from conventional therapies,
    and to relieve symptoms related to their illness.
      Various historic and sociopolitical exigencies have
    contributed to the popularity of Ayurveda use for people
    living with HIV-AIDS.

   Early in the struggle with HIV, pharmacologic treatments
    were limited and often were accompanied by severe
    negative side effects that precluded their use.

    Later, with the advent of highly active antiretroviral
    therapies (HAART), access to these expensive therapies
    was limited for many communities.
     THERE ARE MANY REASONS WHY PEOPLE LIVING
         WITH HIV/AIDS USE AYUSH TREATMENTS

    Limitations of Anti-retro Viral Drugs to be used in our
     country include

    1 Restricted availability in our country.
    2. Major side effects
    3. High cost

    The physicians who work in integrated clinics that
     provide both conventional and complementary services
     may refer patients to these clinics for pain management,
     to learn adaptive coping strategies, to manage chronic
     and serious medical illness, and to manage HIV-related
     symptoms.
    The social role of Ayurveda among people living with HIV-AIDS has been
    examined.

   Some studies have examined the effectiveness of Ayurveda on symptom
    management and improvement of quality of life .

   The management of HIV-related symptomatology has become important
    because people living with HIV-AIDS are living longer as a result of HAART.

     Acceptance that a cure for HIV will not be discovered in the near future has
     justifiably shifted attention to quality of life concerns for people living with
     HIV-AIDS and consequently redirected attention to improving the
     management of HIV-
    related symptoms

   In addition, individuals who choose not to use HAART, who have limited
    access to conventional treatments, or who cannot tolerate the side effects of
    HAART (highly active anti retro viral therapy) may turn to Ayurveda for relief
    of HIV-related symptoms.
    AYURVEDA PROVIDES …..

-a comprehensive individualistic approach for the selection
of appropriate therapy considering the body as a whole not
merely treating the disease

Besides this Ayurvedic
-Rasayana
-Swastavritta
-Sadvritta

provides various drugs /counseling regimens to combat
stress related problems there by improving immunity and
QOL.
Kamya Rasayana:        To promote general, physical and mental
                       health(QOL)

Naimittika Rasayana:   Used to cure some particular
                       diseases(Disease oriented)

Ajasrik Rasayana:      Used in the daily routine of life to promote the
                       general health(QOL)

Achara Rasayana:       Practice of good conduct and desirable
                       behavior in every aspect of life(QOL)
D
I
V
E
R   •RASAYANA-BALAKARA           (IMMUNO MODULATORY)
    •OJOVARDHAKA              (IMMUNO MODULATORY/POTENT
S                                   MICRO NUTRIENT)
I   •AYUSKARA                (ADPTOGENIC/ANTIOXIDANT)
F   •AYUSHYA                    ( ADAPTOGENIC)
    •INDRIYA BALAPRADA         (SUPPORTS THE SENSORY
I
                                   AND MOTOR SYSTEMS)
E   •SMRITIKARA              (MEMORY BUSTER)
D   •VRISYA                     ( APHRODISIAC)
    •VAYASTHAPANA           (ANTI AGING ACTION)
E
    •PUSTIKARA / BRIMHANA     (POLYTROPIC TISSUE
F                                  TONIC)
F
E
C
T
S
STRENGTH OF AYURVEDA -
  EXPERIMENTAL BASIS
                   PROPHYLAXIS
    RECONSTITUTION OF GENERAL IMMUNE
            RESPONSIVENESS


•   Ayurvedic preparations act primarily by activating
    the macrophages.

•   It increases the phagocytic activity of macrophges
    and also induces expression of MHC-II antigens
    indicating enhancement of their antigen-presenting
    ability.
                                                     Reconstitution of
                                                     general immune
     AYURVEDIC
  Agents with putative                               responsiveness
        General
immune enhancing activity




Increases the phagocytic
 Activity of macrophages




                       Induces       EXPRESSION
                       OF      MHC-II     antigens
                       indicating enhancement Of
                       their
                                   .
                                antigen-presenting
                       ability
 AYURVEDIC PREPARATION, AS REPORTED MAY BE
 MEDIATED BY ACTIVATION OF CELLULAR IMMUNE
                RESPONSES

•In vitro, treatment of mice splenocytes with Ayurvedic
preparations stimulated the production of IL-2, IFN-
Gamma and TNF-Alpha reflecting activation of Th-1 type
of T cell responses.

•Since Th-1 type of response has been implicated with the
cell mediated immunity the therapeutic effects of
Ayurvedic preparation, as reported may be mediated by
activation of cellular immune responses.

• Infact, the antimicrobial properties of Ayurvedic
preparation have found to be mediated by the immune
system.
                                             Ayurvedic
   Splenocytes +                           Preparation,
     Ayurvedic                            As reported may
    preparations                           be mediated
                                          by activation of
                                          Cellular immune
                                             Responses


      Stimulated
    the production
of IL-2, IFN-Gamma
   and TNF-Alpha




                            Activation of
                     Th-1 type of t cell responses.
References
1. Bhupinder Singh et al – Ind.J.Pharmacol 13(1): 96, 1981.
2. Rege, N. et al, Indian Drugs, 21(12): 544-546, 1984.
3. Chopra R.N. et al, Gloss. Ind. Med. Plants CSIR, N. Delhi,
   244, 1956.
4. Thatte U M et al.J.Post.grad.Med.1994; 40:202-3
5. Singh N., Curr. Med. Pract. 23(1) 50,1981.
6. Singh N, Int.J.Crude Drugs Res. 29: 29, 1982.,Singh N. et al
   Int.J. Crude Drugs Res. 24: 90, 1986
      AIDS AND AYURVEDA


•In AIDS the patient losses something essential.
The cellular immunity becomes defenseless
against the pathogens and suffers from various
clinical manifestations.

•These manifestations are similar to that of
OJOKSHAYA or          BALAKSHAYA patients,
depicted in Ayurvedic classics.
   OJAS         AIDS AND AYURVEDA




AETIOLOGICAL                      OJO
  FACTORS                       KSHAYA-
                                 AIDS

          DHATU
   KSHAYA/DAURBALYA
          Cellular
         immunity
    becomes defenseless
    against the pathogens
Administrating the rasayana medicaments meant for
ojovardhaka, balavardaka (immuno modulation/adoptogenic
and Nourishment) would help in Promote the process of
dhatu poshana and enrich ojus and thus leads to improve
the vital strength and immunity or vyadhi kshamatva (non-
specific immunity) ultimately contribute in
• managing symptoms
• preventing Ois
• stress
• improving QOL.
OJOVARDHAKA
  RASAYANA
   DRUGS




          OJO VARDHANA
             IMMUNO
           MODULATION
           ANTI STRESS
           ANTIOXIDANT
         MICRO NUTRIENT
      SYMPTOM MANAGEMENT
                           IMPROVED
                              QOL

       DHATU
     VARDHANA
     IMPROVED
       TISSUE
     FUNCTIONS
Methodology -Development Of
      AYUSH QOL-2
-Keeping the global prevalence of HIV/AIDS and
potentials of Ayurveda in view, the council has formulated
and developing        AYUSH QOL-2            for symptom
management, Improvement of quality of Life through
extensive pre clinical standardization /safety /targeted
activity                                           studies.
     Objective
-The primary objective is to assess the safety
and therapeutic efficacy of AYUSH QOL-2, in
the symptom management, Improvement of
quality of Life, To study the immunological
responses of the therapy in HIV/AIDS patients
with    CD4+Tcell count ranging from 200-
450/cu.mm.
SCHEMATIC REPRESENTATION OF DEVELOPMENT


                    Literary Survey


          Formulation of Hypothetical Basis


Formulation of Coded Drugs for identified conditions
Pre-clinical standarsation, toxicity, biological activity
                     (Completed)



  Drafting of specific Protocols on each condition


   Approval by Task Force of Experts (Completed)


                     Clinical Trial
  Drug preparation and standardization
The coded drug AYUSH QOL-2 has been
prepared and standardized by council
adopting the WHO/Global norms(including
microbial growth, estimation of pesticides,
presence of adulterants, heavy metals etc).
                STANDARDIZATION AYUSH – QOL-2
Ayush –   Description: Dark brown moderately fine powder with characteristic
 QOL-2                                smell.
                                        Parameters
                     Ash %                      11.63       11.60      11.62
              Acid-insoluble ash %              0.79         0.30       0.63
           Water-soluble extractive %           51.39       53.61      52.50
          Alcohol-soluble extractive %          21.75       22.33      22.04
           Loss on drying at 105C %            14.10       14.80      14.45
              pH (5% aq. solution)                        4.60
               Bulk density g/cc                          0.55
                Tap density g/cc                          0.63
                   Calcium %                    0.30        0.295       0.30
                 Total sugar %                  12.37       12.44      12.41
               Reducing sugar %                 5.65         5.69       5.67
             Non reducing sugar %               6.72         6.75       6.74
                   Sulphur %                    1.65         1.72       1.69
                   Calcium %                    0.30        0.295       0.30
Microbiological analysis
Total viable aerobic count              3.3 x 103 col/g
Total Enterobacteriaceae                      Nil
Total fungal count                            Nil

Test for specific Pathogen
E. coli                                       Nil
Salmonella sp.                                Nil
S. aureus                                     Nil
Pseudomonas aeruginosa                        Nil

Lethal dose                  No mortality and toxic symptoms upto
                             a dose level of 5 g/kg body wt.


TLC                                         Done
       TLC profiles of ingredients




 Toluene : Ethyl Acetate   Chloroform : methanol
93 : 7                            90 : 10
TLC profiles of ingredients




      Benzene : Ethyl Acetate
                     2:1
TLC of Ayush QOL - 2




  Solvent system: n-Butanol : Acetic acid : Water 63:27:10
    SAFETY STUDIES



The preclinical safety and toxicity (Acute/Sub-acute)
  studies have been conducted adopting
  International norms and revealed its safety.
     BIOCHEMICAL PARAMETERS (MEAN  SE)
          Blood Glucose   Serum                SGOT              SGPT
          (mg %)          Creatinine           (U/L)             (U/L)
                          (mg %)

          14 d    28 d    14 d        28 d     14 d     28 d     14 d     28 d

CONTROL   82.75   81.5    0.8         1.05     177.75   150.25   76.5     65.75
                                                                   
          10.80   9.6           0.0       0.00 15.84    8.42     7.39     12.53
                                081       64
TD        82.75   81      0.8         1.05     157      165.5    70.25    66.5
                                                                   
          7.87    6.95    0.001       0.005    9.7      1.7      7.37     9.32

AD        88.75   85      0.8         1.02     185.75   163.25   81.25    65.25
                                                                   
          9.1     8.34          0.0       0.00 5.58     15.37    15.213   6.48
                                091       25
HD        94.25   91.5    0.62        1.05     158.5    151.5    53.5     50.5
                                                                   
              10. 9.53    0.0025      0.005    9.68     10.44    4.9      4.55
              25
                HAEMATOLOGICAL PAREAMETERS (MEAN  SE)
                          CONTROL       TD             AD              HD


Hb               14 d     12.8 ±0.045   12.3 ± 0.41    12.5 ± 0.31     12.1 ± 0.39
(g %)
                 28 d     13.3 ± 0.44   11.8 ± 0.65    12.1 ± 0.45     11.9 ± 0.5
PCV              14 d     50.5 ± 4.01   48 ± 2.34      50 ± 5.01       48.2 ± 3.06
(%)
                 28 d     57.5 ± 7.48   51.2 ± 6.01    46.7 ± 2.59     48.2 ± 2.32
TRC              14 d     4.3 ± 0.006   4.6 ± 0.009    4.1 ± 0.26 **   4.4 ± 0.32*
(106 / cu.mm)
                 28 d     4.8 ± 0.17    4.3 ± 0.12     3.4 ± 0.15      3.9 ± 0.23

TLC              14 d     4.8 ± 0.31    4.7 ± 0.41     5.6 ± 0.27      4.8 ± 0.23
(103 / cu.mm)
                 28 d     5.2 ± 0.11    5.1 ± 0.32     4.8 ± 0.43      5.3 ± 0.38
POLY             14 d     40.7 ± 4.46   32.2 ± 3.35    43.2 ± 1.43     37.5 ± 2.84
(%)
                 28 d     37.7 ± 0.85   46.5 ± 1.84*   30.5 ± 3.30     36.5 ± 3.17

LYM              14 d     59.2 ± 4.46   67.7 ± 3.35    56.7 ± 1.43     57.7 ± 1.91
(%)
                 28 d     62.2 ± 0.85   53.5 ± 1.84*   69.5 ± 3.3      63.5 ± 3.17
PT               14 d     11 ± 0.35     12.25 ± 1.26   13 ± 1.47       11 ± 0.7
(Sec.)
                 28 d     9.25 ± 0.32   9.37 ± 0.55    10.62 ±0.55     11 ± 0.25
          MEAN ORGAN WEIGHT (% BODY WEIGHT) SE

          Liver          Spleen           Kidney           Heart           Teste   ovary
                                                                           s
          Mal     Fema   Male Fema        Male Fema        Male Femal
          e       le          le               le                  e

Control   4.23    4.51   0.31 0.25        1.18     0.8     0.57    0.54    1.27 0.117
                                                                        
          0.2     0.12   0.001 0.001      0.00     0.009   0.00    0.002   0.002 0.012
                         1                27       3       35      5
TD        4.87    4.27   0.46     0.36    1.04     0.86    0.71    0.47    1.55 0.096
                                                                        
          0.28    0.11   0.00     0.008   0.00     0.003   0.111   0.004   0.108 0.004
                         58       5       44       4       3       3       9
AD        3.93    3.97   0.27     0.29    0.96     0.91    0.6     0.46    1.42 0.096
                                                                        
          0.16    0.14   0.00     0.001   0.00     0.001   0.00    0.003   0.008 0.006
                         28       8       68       6       51      8       5
HD        3.67    4.44   0.25     0.28    0.9      0.82    0.42    0.47    1.69 0.101
                                                                        
          0.11    0.22   0.00     0.001   0.00     0.003   0.00    0.003   0.005 0.01
                         18       8       12       2       17      4       6
HISTOPATHOLOGICAL PROFILES
Section of Intestine showing normal villi
lined by columnar cells (VC, Female).
   Section of kidney showing normal
glomeruli (Ayush QOL 2(TD), Female).
Section of Lung normal alveoli. (VC, Female)
Section of Lung showing thickening of interstitial tissue
                   and collection of
           lymphocytes around peribronchial region.
             (Ayush QOL 2 (AD), female).
Section of Liver showing normal portal areas
       and hepatocytes. (VC, Female).
Section of Ovary showing normal graffian
      follicle and luteal cells. (VC).
 Section of Spleen showing normal lymphoid
follicles and germinal centres (VC, Female).
Section of Stomach showing normal mucosal
glands lined by columnar cells (VC, Male).
Section of Testis showing normal seminiferous
                 tubules (VC).
       Targeted Biological activity Studies


- The /Biological activity study reveals significant
 immunomodulator, adaptogenic activities(antagonized
 the effect of      Cyclophosphamide and       confirmed
 immunomodulatory      effect * P<0.001 ) which are
 essential for improvement quality of life and symptoms
 management in HIV/AIDS.
EVALUATION OF IMMUNOMODULATORY ACTIVITY OF
AYUSH QOL - 2
OBJECTIVE:
To evaluate the immunomodulatory activity of Ayush Formulations in
different animal models.
MATERIALS AND METHODS:
Materials:               Ayurvedic formulation Ayush QOL-2
Animals:                 Albino Rats.
Quarantine: All animals were acclimatized to laboratory conditions for
7 days prior to study initiation. Animals were observed for general health
and suitability for testing during this period. The healthy animals were
selected after the health screen conducted by Veterinary physician.
FORCED SWIMMING TEST
                                                INFLUENCE OF AYUSH QOL-2
                                            ON FORCED SWIM TEST IN ALBINO MICE
                             250.00
                                                                 Fig-1
                                                                                     11th   12th   13th
                             200.00
         IMMOBILITY PERIOD


                                                                         *   *   *
             (Seconds)

                             150.00


                             100.00                                                          *
                                                                                                   *   *
                              50.00


                               0.00
                                      CONTROL      AYUSH QOL-2        AYUSH QOL-2       CYCLOPHOSPHAMIDE
                                                                   +CYCLOPHSPHAMIDE
                              GROUP




INFERENCE
1. Cyclophosphamide has significantly decreased the immobility period when compared to control *
P<0.001
2. Ayush QOL-2 has antagonized the effect of Cyclophosphamide and confirmed
   immunomodulatory effect * P<0.001
TAIL SUSPENSION TEST
                                            INFLUENCE OF AYUSH QOL-2 ON
                                                TAIL SUSPENSION TEST
                                                                                                       11th   12th           13th

                     250.00


                     200.00
                                                                         *           *         *
 IMMOBILITY PERIOD
     (Seconds)




                     150.00


                     100.00
                                                                                                               *
                      50.00                                                                                              *         *

                       0.00
                              C ON T R OL           A Y U S H Q O L- 2       A Y U S H Q O L- 2               C Y C LO P HO S P HA M I D E
                                                                         +C Y C LO P HS P HA M I D E
                     GROUP




INFERENCE
 I.Cyclophosphamide has significantly decreased the immobility period
   when compared to control * P<0.001
 2.Ayush QOL-2 has antagonized the effect of Cyclophosphamide and
  confirmed immunomodulatory effect * P<0.001
NEUTROPHIL COUNT
                                               BLOOD NEUTROPHIL COUNT AFTER
                                           14 DAYS ADMINISTRATION OF AYUSH QOL-2

                        12.00

                        10.00
NEUTROPHIL PERCENTAGE




                          8.00

                          6.00
                                                                                                                 *
                          4.00

                          2.00

                          0.00        C ON T R OL      A Y U SH Q O L- 2         A Y U SH Q O L-        C Y C LO PHO SPHA M I D E
                                                                           2 +C Y C LO PHSPHA M I D E


                         GROUP




                        Inference: 1. Cyclophosphamide has significantly decreased the neutrophils
                                      counts *P<0.001
                                   2. Ayush QOL-2 has antagonized the effect of Cyclophosphamide
                                       and neutrophil count is comparable with central group
The following targeted activity studies are in progress

1.To determine the effect of Aush QOL-2 on body weight and
hematological parameters such as TLC, DLC & Hb.
2.To determine the preliminary effect of Ayush QOL-2 on stem cell
proliferation.
3.To determine the effect on the T Cell subjsets CD4+ & CD8+
cells.
4.To study the effect on macrophage mediated Phagocytosis.
5.To study the effect on the proliferation of lymphocytes.
6.To study the effect of Ayush QOL-2 on the level of cytokines
liberated by TH1 (IL-2, IFN-8), TH2 (IL-4, EL-6, IL-10) and
macrophages (IL-12, ILN-8)
7.To study the effect of Ayush-QOL2 on the expression of TH1 and
TH2, Cytokines.
8. In vitro anti retro viral activity on cell lines.
CLINICAL RESEARCH DESIGN AND
           METHODS
   HYPOTHESIS

• Ayurvedic formulation (Ayush QOL-2) is effective
in improving immunological status in HIV infected
patients and in combating symptoms and improves
QOL in HIV/AIDS patents with CD4+Tcell count
ranging from 200- 450/cu.mm.
Study population

The study participants will be screened from the patients
attending out patient department, based on inclusion
and exclusion criteria defined.

Study Design: Randomized controlled study The
eligible subjects will be randomly allocated in to control
and intervention groups.
Period of study:
•The study will be open for one year. The eligible subjects
shall be recruited in the study till this period. Total period
for completion of the study and data analysis will be two
years from the date of commencement of the study.

Sample Size
• 200 subjects, 100 in each group will be randomly
recruited in treatment and control groups. The treatment
group will receive Ayurvedic drug twice in a day and control
group will be given placebo glucose twice in a day
Inclusion criteria
1.   Age group – 20 to 50 years, irrespective of sex
2.   Seropositive to HIV1 by ELISA (3 tests)
3.   CD4 cell count ranging from 200-450/cu.mm
4.   Able to understand and give written consent
5.   Patients not receiving ART / any other medication
 Exclusion criteria

1. Pregnant or lactating females.
2. Presence of serious systemic illness-Chronic
 renal failure, hepatic failure, cardiovascular
 diseases, endocrinal or metabolic disorders (such
 as diabetes mellitus) etc.
3.Patients suffering from secondary infections or
opportunistic infections like severe chronic diarrhea, all
types of pneumonias, disseminated diseases, brain
abscesses, meningitis, encephalitis, herpes simplex,
herpes zoster, syphilis, pulmonary tuberculosis, and
pneumocystis carinii pneumonia, toxoplasmosis,
cytomegalovirus infection.
4.Patients with neoplasm- visceral lymphomas, invasive
cervical carcinoma. Kaposi’s sarcoma
Criteria for withdrawal and Dropout
•Development/occurrence of a life
threaten illness.
•Severe adverse effect of the drug.
•Non adherence to the treatment
End Points
•Change in symptoms            assessed by the ESAS(The
Edmontion Assessment scale) (patient related Visual
analogue scale,(BreuraE, KuehnN, etal.1993), MSAS
(Memorial Symptom Assessment Short-Form) ( Portenoy RK,
Thaler HT, Kornblith AB, et al 1994).
•Weight change of 5 kilo grams or 10% % of body weight
• Change in in Karnofsky Performance
•Confirmed change in CD4+ T cell count        of 100/mm3,
diagnosed AIDS by WHO clinical criteria of confirmed
CD4+T cells <200 mm3.
Methods
•Special case record forms (CRF) developed are used for
screening of the patients, periodical assessment of clinical
status and assessment of laboratory parameters.
•Besides this ,Separate history form is developed to record
gender, age, address, occupation, educational status, Marital
Status, Family history, history of past ,and present illnesses
risk behavior , sexual behavior.
Methods

•History of exposure towards medical causes like,
Blood transfusion Blood products, Major surgery ,I.V
drug use Needle pricks/ Needle stick, other relevant
causes, Injury etc. Personal History on, active drug
abuse, consumption of alcohol, smoking habit etc will
also be recorded.
Methods
•Change in body weight, incidences of opportunistic infections
Karnofsky performance score and clinical status of the
patient: fatigue, night sweats, anorexia, , diarrhea cough
,breathlessness, headache, vomiting edema, .dermatitis,.
Herpes infection. Will be recorded .

Details of past drug schedule covering name of medication,
total daily duration (in days) and past adverse drug effects
including name of drug details of adverse effects
definite/possible will be recorded

.
Assessment criteria
•The efficacy of the trail drug will be assessed on the basis
of changes in clinical parameters as well as laboratory
investigations.
Clinical parameters
•Weight change
• Karnofsky performance score
•Opportunistic infections
•Monthly Change in symptom will be assessed by the
ESAS( Edmontion Assessment scale) (patient related
Visual analogue scale),(BreuraE, KuehnN, etal.1993),
MSAS (Memorial Symptom Assessment Short-Form) ,)(
Portenoy RK, Thaler HT, Kornblith AB, et al 1994) (Joseph
F. O’Neill et al.2003 ).
    Clinical Parameters              Before the study           Follow-up period (in months)


                                            0           1   2           3          4           5   6

i. Weight

ii. Karnofsky
Performance score

Iii. Incidences of
opportunistic infections

iv. Clinical Status of the Patient

1. Fatigue

2. Fever

3. Night sweats

4. Anorexia

5. Diarrhea

6. Vomiting

7. Headache

8. Breathlessness

9. Cough

10.Oedema

11.Dermatitis

12.Herpes

13.Any other
Laboratory investigations
1. ELISA (3 tests)
2. CD4 count (two initial CD4 T Cell Measurements
   at l week apart)
3. Beta-2 micro globulin level
4. HIV RNA-viral load
5. Hemoglobin %
6. Neopterin level
  
 During study, patients will be screened for HIV/AIDS
depending upon the investigations report and other clinical
signs and symptoms. ELISA will be used for screening of HIV
infections. Patients will be followed for a period of 12 months .
• CD4+ count , (Two (2) CD4 T Cell Measurements at l week
apart )Beta-2 micro globulin level, and Neopterin Viral load
and gm% of Hemoglobin will be investigated at 0 month
with interval of 3 months for 12 months .
• Other hematological, bio -chemical and radiological
investigations will be done at 0 month and 12th month.
Laboratory Parameters       Before the trail                Follow-up period (in months)


                                   0                1ST          3                 6
                                                  WEEK
                                                   only
                                                   CD4
                                                  Count
1.CD4 Count

 2. Beta-2 micro globulin                        ---
level
3 HIV RNA. Viral load                            ---

4. Hemoglobin (gm%)                              ----

5. Neopterin level                               ---

                                                 ---

                             Follow-up period (in months)

             9                         12                            REMARKS
Intervention
• The treatment group will receive Ayurvedic drug
(Ayush QOL-2)twice in a day and control group will be
given placebo glucose twice in a day
•Group I: Trail drug- 2 tablets (510 mg/tab) .
•Group II: Placebo (glucose)- 2 tablets (510 mg/tab)
twice in a day before food with water for 12 months .
 Data monitoring       and Conduct of clinical study


• A Data and safety monitoring board(DSMB) will be established
to carefully monitor the data and side effects during the period of
study and put in a place where by prompt reporting of adverse
events occur.
• The board periodically assesses the data and monitors the study.
• A clinical trial manual will be developed and a short training will
be given to the research staff regarding the conduct of the study.
 General Management

• Patients will be managed on out patient level
only. Physicians on the set (Case record form
(CRF) make periodic assessment.
• Patients will be instructed to avoid other
forms of medicines during the period of trail.
• They should report to the physicians
immediately for appropriate treatment in the
event of adverse relation.
Confidentiality
•Strict confidentiality of all data collected will be
maintained to prevent embarrassment or
Victimization of patients.
•Consent form will be obtained from every patient.

 Data analysis
• The, data on clinical and laboratory parameters
taken into account for diagnosis and for the
assessment will be tabulated and analyzed using
suitable statistical method. (SPSS-VERSION -11)
Thank You

				
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