Summary Report of The clinical Study on
Ganoderma Polysaccharides Bolus

Contents

Part One: Observation on Clinical effects of Ganoderma Polysaccharides Bolus on 50 patients with diabetes
1 Preface
2 Purpose
3 Materials and Methods
4 Results
5 Overall analyses
6 Conclusions
7 References
8 Attachment: Typical cases
Part Two: Thinking on the R&D orientation of Ganoderma Polysaccharides Bolus
Part One: Observation on clinical effects of Ganoderma Polysaccharide Bolus on 50 patients with diabetes type II
[Preface]
Ganoderma is the catholicon, in Chinese medicine therapy, used for treating diverse diseases. Ganoderma Polysaccharide is extracted from ganoderma seeds, demonstrates pharmaceutical activities as anti-cancer, enhancing immunity, protecting liver, regulating level of blood sugar, and is mainly used in treatment of diabetes type II.
[Purpose]
The study, by a clinical controlled test, is to prove the effects of the Ganoderma Polysaccharide on reducing blood sugar, to evaluate its function of improving clinical symptoms of diabetes, and meanwhile to understand preliminarily its safety in use.
[Materials and Methods]
1. Criteria of cases diagnosis
1.2?Diagnosis criteria
According to the diagnosis and classification of diabetes (WHO Non-communicable Diseases Determination Department, Geneva Convention) suggested in the WHO Specialists Consultation Report in 1999, one can be diagnosed as diabetes only if one of the following conditions occurs: venous blood sugar in fasting is over 7.0mmol/L，or over 1.1mmol/L 2 hours after meal.
1.2 Criteria of classification and quantification of clinical symptoms
0~10 criterion is applied for symptom scoring under self-evaluation of the patients.

0         2         4         6         8         10
 
0          slight          medium          severe

2. Criteria of cases choosing
2.1 Inclusion criteria:

1. Under WHO Diabetes Diagnosis Criteria (diabetes type1 and 2)
2. Not yet conforming to the standard level of blood sugar after exercising and diet-control
3. No intake of other sugar-reducing drugs, or not yet conforming to the standard level (FBG>7.0mmol/L, P2BG>11.1mmol/L) after intake of other sugar-reducing drugs
4. Age: 30~70 years
5. Course≥1 year
6. Patients keeping original habits of diet and daily life

2.2 Rejection criteria

1. Patients in a history of Ganoderma allergy
2. Patients conforming to the standard level of blood sugar after exercising and diet-control
3. Patients unable to self-control diet, without a regular life and compliance
4. Patients with complications as severe primary diseases in cardiovascular system, liver, kidney and hematopoietic system, and mental diseases.
5. Patients in diabetes ketosis, ketosis acidosis and severe infected conditions
6. Female patients in pregnancy, pre-pregnancy or lactation

2.3 Criteria of cases filtered out

1. Patients, included, not in the Inclusion Criteria
2. Patients taking other new sugar-reducing drugs (not the drugs taken before inclusion), or not taking the test drug.

2.4 Criteria of cases non-evaluated

1. During the test, patients without good compliance, which influences on evaluation of effectiveness and safety.
2. Patients in severe adverse events, complications and specific physiological changes, not suggested taking the continued test.
3. Patients quitting before the test is finished.
4. Patients without completed personal data, which influences on evaluation of effectiveness and safety.

2.5 Test ending points

1. Patients in severe adverse response during taking the drug.
2. Patients not demonstrating desirable effects of the test drug during the test, with FBG>16.6mmol/L, P2BG>22.2mmol/L, and not meeting a standard level of blood sugar one week after exclusion of inducing factors.
3. Big mistakes of the clinical test plan are found in the test and it is difficult to evaluate the drugs’ effects; or big errors occur during carrying out the plan and it is difficult to evaluate effects of the drug.

3 Drugs
3.1 Drugs suppler：Shenzhen Taitai Pharmaceutical Co. supplying the test drug and the control agent. All of them are tested passed.
3.2 Methods of taking:
Test drug: Ganoderma Polysaccharides, taken with warm boiled water, 50 boluses (1 spoon) a time, 3 times / day
Control agent: Xiaoke （thirst-quenching） Bolus, taken with warm boiled water (post-meal) 5 boluses a time, 3 times / day
3.3 Drug administration: dedicated people for drug distributing, recording, and judging compliance of the subjects taking drugs; the drugs are stored dry in a specific place at room temperature.
4. Methods
Randomized and controlled methods were introduced in the test.?
4.1 Fifty patients with diabetes, in the inclusion criteria, are divided into two groups by the random number method, the test group and the control, which take Ganoderma Polysaccharides bolus and XiaoKe bolus, respectively.
4.2 During the test, the patients are not allowed to replace or add other drugs, that is, not changing the types and doses of original drugs, except for adding the test drug (Ganoderma Polysaccharides). Concerning the patients taking other sugar-reducing drugs besides the test drugs and necessarily taking other drugs related to complications, it is required to record drugs names, dosage, using times and duration in the cases report so as to analyze and report in summary.
4.3 Patients included keeping original habits of daily life and diet
4.4 Four weeks duration
5. Observation index
5.1 Safety index: check blood / urine routine index, EKG, liver / kidney function, respectively, in pre- and post-treatment, and evaluate the safety.
5.2 Effect index: check blood sugar change (FBG, P2BG, HbA1C), urine sugar, blood lipid (TC, TG, HDL), and clinical symptoms improvement, and evaluate the effectiveness. Check FBG in finger-point blood at intervals of one week; FBG, P2BG in venous blood at intervals of one week; check the other index, respectively, in pre and post-treatment.
6. Criteria of effect evaluation
6.1 Criteria of effect of sugar reducing

(1) Evaluation of effect on blood sugar in fastingEffective: decreasing by 10% or higher in comparison with in pre-treatmentNon-effective: not satisfying the above standard level of blood sugar in fasting in post-treatment.
(2) Evaluation of effect on blood sugar 2 hours after mealEffective: decreasing by 10% or higher in comparison with in pre-treatmentNon-effective: not satisfying the above standard level 2 hours after meal.
(3) Evaluation of effects on glycated hemoglobin
Indicated by (medium± standard deviation) in pre and post-treatment

6.2 Criteria of effect evaluation on lipid reducing

(1) Evaluation of effect on cholesterolEffective: the cholesterol level decreasing by 10% up in post-treatment compared with in pre-treatmentNon-effective: the level decreasing in post-treatment not satisfying the above standard level.
(2) Evaluation of effect on triglyceride Effective: the level of triglyceride decreasing by 20% up in post-treatment compared with in pre-treatmentNon-effective: the level decreasing in post-treatment not satisfying the above standard.

6.3 Criteria of effect evaluation on symptoms scores

(1) Evaluation of effect on overall symptoms scores
Effective: scores decreasing rate ≥30％
Non-effective: scores decreasing rate＜30％

(2) Evaluation of effect on single symptom score
Effective: score decreasing ≥1
Non-effective: no score decreasing or increasing

1. t-test, to compare overall symptoms scores between the two groups in pre and post-treatment, checking if there is a significant difference.
2. t-test, to compare the difference of single symptom scores between the two groups in pre and post-treatment, checking if there is a significant difference.
3. t-teat, to compare laboratory indicators for blood sugar changes（FBG, P2BG, HbA1C）between the two groups in pre and post-treatment, checking if there is a significant difference.
4. t-test, c to compare laboratory indicators for blood lipid changes（TC, TG, HDL）between the two groups in pre and post-treatment, checking if there is a significant difference.

9.4 Statistical description of quantitative data each time seeing physicians in the two groups shall be conducted by frequency (constituent ratio). X2-test shall be adopted for changes of the two groups in pre-treatment and post-treatment.
9.5 Quit analysis: X2-test shall be adopted to compare overall non-evaluated cases rate and the quit rate due to adverse events in the two groups.
9.6 Effectiveness analysis: adopt non-parameter method to evaluate effectiveness indexes
9.7 Safety analysis: adopt X2-test to compare of incidence rate of adverse events between the two groups, list description of adverse events in the study; to compare the test results of safety indexes between the two groups in pre and post-treatment, and its relation with the test drug when abnormality occurs.
10 Data management and documents storing

1. Check seriously laboratory test indexes, fill out the table of cases report
2. Store original data and documents

[Results]
1 General clinical data
All patients were from BaoKang Hospital and Guajiasi Hospital under Tianjin Chinese Medicine College. Among them, 25 patients was in the treatment/test group, 12 male and 13 female, and the medium age is 55.68±7.42 years; 25 was in the control group, 13 male and 12 female, and the medium age is 55.30±10.86. The comparison between the two groups is shown in Table 1, which has no statistical difference（P>0.05）. In the test group, one case, a female patient, was ended due to nausea and vomiting acid. There is no statistical difference in vital signs between the two groups（P>0.05）.
Table 1 General dada and comparability analysis

1. Pre- & post-treatment comparison of effect of Ganoderma Polysaccharides Bolus on single symptom score of the patients with diabetes

Table 2

Note：in comparison with in pre-treatment * ：P<0.05；**：P<0.01；***：P<0.001

3 pre- & post-treatment comparison of effect of XiaoKe bolus on single symptom score of the patients with diabetes
Table 3

Note：in comparison with in pre-treatment * ：P<0.05；**：P<0.01；***：P<0.001

4 The two groups comparison of the difference of overall symptoms scores in pre- and post-treatment
Table 4

Note：in comparison with the control group * ：P<0.05；**：P<0.01；***：P<0.001

5 Pre- & post-treatment changes of the index in the Ganoderma Polysaccharides Bolus Group
Table 5

Note：in comparison with in pre-treatment * ：P<0.05；**：P<0.01；***：P<0.001

6 Pre- & post-treatment changes of the index in the XiaoKe Bolus Group
Table 6

Note：comparison in post-treatment with pre-treatment? * ：P<0.05；**：P<0.01；***：P<0.001

7 Comparison of the index changes of post-treatment laboratory examinations on the patients with diabetes between the two groups
Table 7

Note：in comparison with the control group * ：P<0.05；**：P<0.01；***：P<0.001

8 Comparison of overall effects between the two groups
8.1 Effects of reducing sugar

Note：in comparison with the control group, X2＝0.089，P>0.05

8.2 Effects of reducing lipid

Note: in comparison with the control group, X2＝0.83，P>0.05

8.3 Improvement of overall symptoms

Note：in comparison with the control group, X2＝0.14，P>0.05

9 Adverse events records
during the post-treatment and pre-treatment, no significant changes and abnormalities, were found in the test group in terms of blood/urine routine assay, liver and kidney function examination and cardiography. In the test group, one patient had nausea and vomiting acid, and thus was quit.

[Overall Analysis]
In the study, 50 patients with diabetes were included, 25 in the treatment group and 25 in the control group. A significant comparison between the two groups was in terms of demology, blood sugar level, course of diseases, distribution of disease conditions, etc. The valuated indexes included blood sugar in fasting and post-meal, glycated saccharified hemoglobin, blood lipid, liver and kidney function, and clinical symptoms, improvement of physical signs and changes of overall scores. The results indicated that Ganoderma Polysaccharides Bolus lowered the level of blood sugar and lipid of the patients with diabetes, and improved clinical symptoms and physical signs, which had no statistical significance（P>0.05）comparing to Xiaoke Bolus. In terms of relieving of single symptom, the bolus can significantly improve clinical symptoms and physical sign before the treatment, which is significantly different from pre-treatment (P<0.01). The Ganoderma Polysaccharides bolus has some advantages over Xiaoke Bolus in terms of ameliorating blur sight, acroparesthesia, constipation, etc. In the mean time, we found that the bolus has the tendency to reduce cholesterol and triglyceride.
【Conclusion】
Comparing to the XiaoKe Bolus group, no significant difference（P>0.05）of overall therapeutic effects on diabetes was found in the test group using Ganoderma Polysaccharides Bolus, but Ganoderma Polysaccharides Bolus lhas better effects on the diabetes patients in a lower level of blood sugar and with hyperlipemia.??
【References】
1? Zheng Xiaoyu. Clinical Research Guide & Principle of TCM New Drugs, China Medicine and Drugs Technology Press. 2002
2. Zhen Xiaoyu. Training Material of Clinical Test Management Criterion of Drugs, China Medicine and Drugs Technology Press, 2000.
[ATTACHMENT Typical Cases]
Please refer to case report table
Part Two? Thinking on the R&D orientation of Ganoderma Polysaccharides Bolus
Diabetes is now one of the common diseases in the world. Its incidence has a tendency to increase year-by-year, only secondary to high blood pressure and coronary heart disease, which ranks 3rd among the common diseases influencing on human body health.

Currently, diverse drugs for treatment of diabetes appear in the market. The drugs are mainly classified as three types: Western medicine, Chinese medicine and Western-Chinese compound agent. But Western medicine is mostly used in clinical application and few of Chinese medicine agents really have desirable effects on blood sugar reducing. Actually, to some extent toxicity and side effects are definitely followed by long-term Western medicine taking.
Ganoderma is a catholicon in Chinese medicine therapy for many diseases. Ganoderma Polysaccharide is extracted from ganoderma seeds, and has pharmaceutical activities as anti-cancer, enhancing immunity, protecting liver, and regulating level of blood sugar. And current studies indicate that the mechanism of diabetes is, more and more, related to human immune system.
It is found that Ganoderma Polysaccharide has a desirable effect of reducing blood sugar, particularly post-meal blood sugar. It can improve many adverse symptoms, of the patients with diabetes, such as blur sight, acroparesthesia, fatigue, thirsting, easy to hunger and eating a lot, hands and feet numbness, etc. In the mean time, it is found to have the tendency to make levels of cholesterol and triglyceride normal.