And Address / Mudasir Khazir
P.G scholar Dept. Of Ilmul-Advia, National Institute of Unani Medicine, Boys Hostel, Room no. 25, Kottigepalya Magadi Road, Bangalore.560091
2. /
Name of the Institution
/ National Institute of Unani Medicine3. / Course of study and subject / M.D Ilmul Advia
4. / Date of Admission to course / Nov. 03.2010
5 /
Title of the Topic
/ Development of Mizaj inventory for single drugs and its validation by LD50 – A preliminary studyPROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
66.1 / Brief resume of the intended work:
Need for the Study:
Mizaj has been defined as “A resultant state produced after interaction of different states (kafiyat) of such constituents that have divided into minute particles for thorough mixing together”1. Mizaj Advia has remained central to the theory of drug action in Unani system of medicine. Mizaj has been defined in a number of ways to account a general picture of properties of a person, drug or any other object. Human knowledge is an all out effort to assimilate the facts observed by him to present in a frame work that has got not only summarising element, but also predictive nature. Mizaj of human being as well as the drugs serves as conceptual frame to use drugs in a rational way, to predict the effect of drug on body and serve as an indicator of potency of a drug. The mizaj of drugs specifically has been defined in terms of nature and extant of deviation due to drug action from normal state of human body, produced after administration of the drug. For example, a drug is said to be hot or cold in nature when on administration it tends to increase or decrease the heat content or induce such effects in the body which can be attributed to increased heat or coldness respectively1, 2.
The centrality of mizaje Advia warrants its exact evaluation and it becomes more imperative when we have recently got rigorous research tools for evaluation of drug action.
Unani medicine has got its own method of establishing action of drugs. A priori drug is subjected to mizaj assessment by the method of analogy and than it recommends experimentation in humans3. Pre assessment of mizaj by analogy is carried out on the basis of organoleptic characters of drug and by its physico chemical properties. However, the assessment of these characters have greater component of subjectivity. Also there is considerable controversy among scholars about mizaj of certain drugs as a result of which different mizajs have been ascribed to the same drug by different people. This makes it difficult to decide about the actual mizaj of such drugs. These controversial statements of scholars can be owed to lack of clearly defined and objective principles for determination of mizaj. Therefore for universalization and uniformity in Mizaj description of drugs some objective principles and parameters need to be developed and redefined.
This study is directed towards development of an inventory for mizaj that is more objective in nature as compared to the existing criteria which is more subjective. The importance of such a study is that after development of objective inventory for mizaj, the confusion regarding Mizaj description of a drug is less likely and experimental phase of drug development will be more precise and cheaper in terms of cost and labour. This may also harmonise the Mizaj of drugs tested by different people independently.
Review of literature:
Mizaj has been an important point of discussion among both ancient and modern Unani scholars. While ancient scholars defined mizaj of drugs in the light of its way of behaviour and nature of effects produced in the body, the modern scholars try to correlate the concept of Mizaj with new scientific knowledge of physics, chemistry, biochemistry, medicine and other fields. The fact is that we have still not been able to clearly define and understand the concept of mizaj objectively4.
Mizaj of drugs has been discussed with little variation in almost every authentic classical works like Al-Qanoon2, Kitabul Mukhtarat Fil Tib5, Kullyat Ibn Rushd6 and various other classical books.
Al-Qanoon has defined Mizaj as ‘a resultant state produced after interaction of minutely divided particles, Arkan [elements] with their different qualities.1 A motadil drug has been defined as a drug which does not produce any visible effect in the body after repeated administration. Similarly it says about hot/cold drug that a drug is considered hot or cold in mizaj when on administration it produces an amount of heat which is more than or less than the normal heat of the body respectively. Drugs of wet and dry nature have been defined in the same manner. All drugs have been further classified into four degrees as per the severity and intensity of their effects on the body. The severity of effect increases from 1st to 4th degree of mizaj and as such a drug in 4th degree of mizaj is considered as poisonous one7.
Mizaj assessment has been carried out through experiment, analogy and on the basis of certain physical properties of drugs like taste, smell, colour and viscosity. But experimentation on human body under strict guidelines which are mentioned in books like Al-Qanoon is considered to be the only reliable way of assessing Mizaj. The possible mizaj of a drug on the basis of its physical features as mentioned above acts only as a supportive criteria in this regard 2.
Methodology:
The assessment of mizaj will be sought by framing an inventory based on the information from classical books. Information field will be collected from the existing classical books and various domains will be formed wherein appropriate question (items) will be selected. The responses will be rated according to the importance it has in the determination of mizaj. The responses will be pre defined so as to minimize the subjectivity in the response. Each item will be scored and scoring will be carried out using equal interval rating scale. On the other hand the mizaj of the drug will be sought from the classical authors and LD50 of their chemical constituents will be collected from the Journals. Those selected drugs which have not been studied for LD50 will be subjected to acute toxicity tests for LD50 following new OECD guidelines 8. Analysis for correlation of the mizaj score with statement of classical authors and with LD50 will be carried out. Moderate to high correlations will be treated as valid statement for the Inventory.
Item selection:
The items or the questions will be framed under two domains- Organoleptic characters and physicochemical properties as emphasized by Unani physicians; and they will be rated for their appropriateness by five Unani experts. Inter-rater judgment and the suggestions for any modification will be taken under consideration for the final item selection. Index of discrimination is the ability of the item on the basis of which the distinction is made between superior and inferior responses9. Index of Item discrimination will be carried out by correlation technique through item – total correlation10.
Reliability of the inventory:
The reliability of the inventory will be established by comparing the mizaj scores interpretations with the consensus of more than three classical reputed authors about the mizaj and degree of mizaj of the drugs. Correlation greater than 0.8 will be considered as sufficient agreement of the two methods of mizaj assessment11.
Validity of the inventory:
The validity of the inventory will be established by external criterion The correlation of LD50 and the mizaj degree will be taken into consideration for this purpose, validity coefficient of more than 0.6 will be considered sufficient for the validation of the inventory11.
Selection of drug:
Number of drugs to be selected for the study will be 80 commonly available plant drugs, among which four groups of 20 drugs each will be selected according to the degree of mizaj equally divided into hot and cold category of mizaj. The LD 50 of the drugs will be noted from the accepted journals/official sources; however the drugs where LD 50 is not available for crude forms toxic doses of the chemical constituents will be noted and extrapolated to crude forms. If for a particular drug toxic dose information is not available, that drug will be subjected to toxicity test.
Acute toxicity test:
The drugs which have no available information as regard to their toxic dose will be subjected to acute toxicity test as described by Ghosh12. The drugs will be administered once orally at various dose levels to group of eight mice of both sexes about equal in number, which have been fasting over night (about 18 hours). Before actual LD50 determination, a pilot study will be conducted on a small group of mice mainly to select the dose range for the subsequent study. The compound will be administered orally to pair of mice in ascending and wildly spaced doses. The administered mice will be observed continuously for two hours, and then occasionally for further four hours and finally over night mortality recorded. The dose killing one out of two mice in the experiment will give a very approximate LD50, or the range between the maximum non lethal and minimum lethal dose, a final more reliable LD50 assay will be planned using at least three or four dose level with in this range with eight number of animals in each groups. In this test a single dose of the drug will be used in each animal on one occasion for determination of LD50 or median lethal dose (MLD) and note gross behavior.
List of References:
1. Ibn Sina. Kuliyate Qanoon. (Urdu translation by HK. Kabiruddin). Ajaz Publishing House, 2006: p 28-36
2. Ibn Sina. AL Qanoon Fil Tib, (Urdu translation by Kantoori GH).Vol V. New Delhi: Idara Kitabul Shifa; 2007:p 13-22
3. Ibn Sina. AL Qanoon Fil Tib. (English translation)Vol II. Dept of Islamic Studies, Jamia Hamdard, New Delhi: 1998 :p 2-9
4. Ishtiyaq SA. Kuliyat Asri,New Public Press, New Delhi Vol. I. 1982: P 34-38
5. Baghdadi AIH. Kitabul Mukhtarat fil Tib. ( Urdu translation) CCRUM, New Delhi, Vol. I: 2005;23,24
6. Ibn Rushud. Kitab-ul-Kuliyat,(Urdu translation) CCRUM, New Delhi 1987: 212-217
7. Mohamad AHK. Bustanul Mufardat. New Delhi: Idara Kitabul Shifa ; 2002: p 4-9
8. Anonymous. OECD (2000). Guidance Document on Acute Oral Toxicity. Environmental Health and Safety Monograph Series on Testing and Assessment No.24.
(www.oecd.org/DATAOECD/17/51/1948378.PDF)
9. Blood DF and Budd, WC (1972) Educational measurement and Evaluation. New York, Harper and Row, 60-61
10. Lindquist, FF. (1951) Educational measurement. Washington: American council of Education, 30-35.
11. Cureton, EE (1965). Reliability and Validity: Assumptions and Experimental Design. Educational and psychological Measurement, 25: 327-46.
12. Ghosh MN. Fundamentals of Experimental Pharmacology. Calcutta: Scientific Book Agency; 1984.
10 / Does the study require any Investigation or
intervention to be Conducted on patient or
other Humans or animals?
11 / Has ethical clearance been obtained from your institution?
12.1 / Signature of Candidate
12.2 / Remarks of the Guide
12.3 / Name & Designation of Guide
12.4 / Signature
12.5 / Co- Guide
12.6 / Signature
12.7 / Head of Department
12.8 / Signature
12.9 / Remarks of the Director
12.10 / Signature