Nghiên cứu độc tính và tác dụng của cao lỏng HVT trên hội chứng rối loạn lipid máu tt tiếng anh

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RATIONALE
Cardiovascular disease has been a major health concern in the world,
with the leading cause of mortality and disability. According to estimates by the
World Health Organization, there are about 17 million people died from
cardiovascular disease every year, mainly caused by atherosclerosis.
Dyslipidemia pattern is one of the most important risk factors but a
variable risk factor for the formation and development of atherosclerosis.
Modern medicine has many drugs used to treat dyslipidemia, but some of them
also have undesirable effects such as muscle pain, muscle cramps, impaired
liver function, etc.
HVT remedy is made up of three commonly used medicinal herbs:
Folium Nelumbinis nuciferae, Cleistocalyx operculatus Roxb and Pericarpium
Citri reticulatae perenne, are prepared into liquid form which act on improving
healthy qi, resolving phlegm-dampness and fortifying the spleen. Currently,
there are no studies evaluating the effects of treatment of HVT on dyslipidemia
pattern. To demonstrate the effects and toxicity of HVT, as a scientific basis
towards the ability to widely use this product in clinical practice, we conduct
the research on the topic “A study on the toxicity and effectiveness of HVT
liquid drug on dyslipidemia pattern” with the following goals:
1. To study the acute toxicity and semi-chronic toxicity of liquid HVT.
2. To study the effect of dyslipidemia adjustment of liquid HVT in
experimental animals.
3. To evaluate the therapeutic effects and unwanted effects of liquid HVT
in patients with dyslipidemia caused by internal phlegm-dampness.
PRACTICAL SIGNIFICANCE AND NEW CONTRIBUTIONS
OF THE STUDY
Practical significance
Although the treatment of dyslipidemia with modern medicine is
effective, it also causes some unwanted effects. Therefore, the search for

remedies derived from herbs, with few tastes, effective and safe is always a
necessity as well as a research direction that is of interest to domestic and
international scientists.
Scientific significance
The dissertation has been systematically studied in both experimental
and clinical practice. The drug is produced in liquid form with ingredients of
three traditional medicine drugs which are originated from Vietnamese
traditional medicinal drugs, easy to find and convenient for use in treating
dyslipidemedia. The study has provided scientific evidence on the effect of


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dyslipidemedia adjustment as well as unwanted effects (if any) on experimental
and clinical issues.
The applied research of a remedy in treatment has made a contribution
to the clarification of the theory of traditional medicine. At the same time,
gradually modernizing traditional medicine is also a scientific and practical
significance.
ORGANIZATION OF THE STUDY
The dissertation consists of 128 pages, of which: Rationale (2 pages), Literature
review (32 pages), Subjects and research methods (18 pages), Research results
(43 pages), Discussions (30 pages), Conclusions (2 pages), Recommendations
(1 page). There are 145 references used in the study, of which there are 53
documents in Vietnamese, 92 documents in English and 2 documents in
Chinese. The dissertation has been presented and illustrated through 61 tables, 9
charts, 18 pictures, 5 diagrams and appendices.
Chapter 1. LITERATURE REVIEW
1.1. Dyslipidemia from modern medicine point of view.
1.1.1. Definition of dyslipidemia

Dyslipidemia is a condition of the increase of either total cholesterol (TC) or
triglyceride (TG) or both, or the decrease of high-density lipoprotein cholesterol
(HDL-C), or the increase of low-density lipoprotein cholesterol (LDL-C) which
increases the process of atherosclerosis.
1.1.2. Causes of dyslipidemia
The cause of dyslipidemia can be primary (due to genetic diseases) or
secondary (due to eating habits, lifestyles or some pathologies). Secondary causes
may contribute to dyslipidemia due to the causes of the primary which become
more severe.
1.1.3. Treatment of dyslipidemia
* Treatment principles:
- Lifestyle changes (proper diet, exercise regime) are the basic and core
problem in treatment. The time to evaluate the effectiveness of lifestyle changes is
usually 2-3 months.
- Medications when needed.
- Treatment goals based on tests and assessments of patient risks, in which
LDL-C is recommended as the first treatment target. TC is the target for treatment
if there are no other tests, while non-HDL-C or ApoB is the second target.
* Drugs for dyslipidemia treatment according to modern medicine:
Based on the mechanism of action, drugs for dyslipidemia treatment are
divided into 2 main groups as follows:


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- The group that reduces lipid synthesis: Statins, fibric acid (Fibrat), and
nicotinic acid (Niacin)
- The group that reduces absorption and increases lipid elimination: bile acid
sequestrants (Resin), cholesterol absorption inhibitor (Ezetimib)
- In addition, some other drugs are used to treat dyslipidemia, such as

PCSK9 inhibitors, MTP inhibitors, CETP inhibitors, and so on.
1.2. Dyslipidemia from traditional medicine point of view.
1.2.1. Causes
In terms of traditional medicine, dyslipidemia is caused by the following
syndromes: irregular congentinal factors, uncontrolled diet leading to spleenstomach disharmony; internal injury leading to liver-gallbladder damage; the
debilitation of the elderly leading to the debilitation of source qi liver. When the
function of the viscera and bowels is disordered, it causes phlegm-dampness
pattern.
1.2.2. Disease mechanism
The process of disease development consists of three stages:
- The dysfunction of spleen and kidney affects the metabolism of water and
food substances causing endogenous dampness turbidity pattern.
- The function of damaged viscera and bowels causes endogenous phlegmdampness turbidity and pattern of depressed dampness transforming into heat.
The symptom in this stage is phlegm turbidity depressing fire.
- The development of the disease causes binding of phlegm stasis, qi
damage, yin damage, and yin-yang disharmony which can lead to a more serious
condition and damage of the visceral organs, resulting in complications.
1.2.3. Clinical classification in terms of traditional medicine
- Pattern of internal phlegm-dampness: Body obesity, headache, chest pain,
abdominal distention, nausea or vomiting, dry mouth without being thirsty, thin
limbs, heavy limbs, pale swollen tongue, white greasy coating tongue, slippery
pulse.
- Pattern of Phlegm-heat and fu-organ excess syndrome: Strong well-being,
heavy head, irritability, red face, red eyes, bitter mouth, tight chest,
uncomfortable, indigestion, constipation, pink red tongue, yellow greasy coating
tongue, slippery pulse.
- Pattern of Spreen-kidney yang deficiency: puffy face, pain in back and knees,
fear of cold, mental fatigue, indigestion, sloppy stool, night urination, pale
tongue, edge of tongue with teeth, thick white fur tongue, slow sunken pulse.
- Pattern of liver-kidney yin deficiency: Pain in back and knees, irritable people,

head pain, dizziness, fatigue, tinnitus, nightly sweats, dry and thirsty mouth, red
tongue, thin fur tongue, ripid fine pulse.


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- Pattern of phlegm stagnation and blood statis: Fatty body, heavy and
numbness limbs, tight chest, headache, dizziness, purple fur & spotted tongue,
thick fur tongue, strink-like and slippery pulse or rough pulse.
- Pattern of liver depression and spleen deficiency: Tight pain in the edge of
ribs, unstable pain, headache, dizziness, irritability, poor appetite, mental fatigue,
sloppy stool, menstrual disorders, pale tongue, thin fur tongue, strink-like pulse.
1.3. Overview of therapeutic remedy research.
According to folk experiences and documents on traditional medicines, there
are many medicinal herbs, remedies for treatment of phlegm-dampness pattern,
which are proved to be clinically effective in adjusting dyslipidemia. Most
remedies have too many herbs or they derive from abroad, making it difficult for
patients to take drugs for the prolonged treatment. HVT remedy is based on the
theory of traditional medicine and some studies of modern medicine on the
effectiveness of each herb. HVT remedy is made up of Vietnamese medicinal
herbs, so they are easy to find, easy to use and have been commonly used by
people:
+ Folium Nelumbinis nuciferae which acts on upbearing the clear, dissipating
stasis, moving water, removing phlegm-dampness. There have been many
domestic and foreign studies published results that Folium Nelumbinis nuciferae
has the effects of lowering blood pressure, lowering blood sugar, preventing
obesity, adjusting dyslipidemia, so it has the effect of preventing atherosclerosis.
+ Cleistocalyx operculatus Roxb is a drink that has been used for many
generations in Vietnam as well as in many countries around the world. It has the
effect of fortifying the spleen and removing the excess. There have been a lot of

studies on Cleistocalyx operculatus Roxb which have found that it is not only a
healthy drink, but also significantly effective in many activities: anti-microbial,
anti-dyslipidemia, lowering atherosclerosis, lowering blood sugar, inhibiting the
development of cancer cells, improving congestion, soothing gallbladder,
releasing pain and anti-allergy.
+ Pericarpium Citri reticulatae perenne is effective in fortifying spleen,
regulating qi, and drying dampness to resolve phlegm. Pericarpium Citri
reticulatae perenne is widely used as medicine and food in Vietnam and many
countries in the world. This herb has been presented in more than 10% of
Chinese pharmacopoeia formulations. There have been many studies proving the
effect of Pericarpium Citri reticulatae perenne in treating dyslipidemia, reducing
obesity and preventing atherosclerosis.
The effects of HVT remedy are fortifying spleen, regulating qi, drying
dampness and resolving phlegm.
Chapter 2 . SUBJECTS AND METHODS OF RESEARCH
2.1. Research materials


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2.1.1 Experimental drug: HVT remedy is produced in liquid form with a ratio of
1:1 (g/ml), bottled with volume of 240ml (Folium Nelumbinis nuciferae 90g,
Cleistocalyx operculatus Roxb 90g, Pericarpium Citri reticulatae perenne 60g) by
Department of Pharmacology, Military Institute of Traditional Medicine, meeting
the basic standards.
2.1.2 Control drug (Statin group): Experimental study: Atorvastatin 10mg
(Lipistad-Stada Vietnam). Clinical study: Atorvastatin 10mg (Lipitor-Pfizer
Pharmaceutic Germany).
2.2. Subjects of research
2.2.1. Research subjects on experimental study

- White Swiss mice, healthy, weighing 200 ± 20g, provided by National
Institute of Hygiene and Epidemiology.
- White Wistar rats, healthy, weighing 150 – 180g, provided by Military
Medical University.
2.2.2. Research subjects on clinical study
- Criteria for selecting patients
* In terms of modern medicine: the patients over 40 years old, regardless of
occupation and gender. The patients are diagnosed with dyslipidemia when they
have at least one of the following four abnormal indicators:
TC > 5.2 mmol/l, TG > 2.3 mmol/l; LDL-C > 3.4 mmol/l; HDL-C < 0.9 mmol/l.
* In terms of traditional medicine: the patients have manifestations of phlegmdampness such as obesity, pale swollen tongue, white greasy coating tongue,
dizziness, severe head pain, numbness of limbs, fatigue, palpitations, insomnia,
slippery pulse or string-like pulse.
- Exclusion criteria: the patients with chronic diseases, liver failure, renal failure,
secondary dyslipidemia syndrome or being taking drugs that affect blood lipid
index; the patients with hypersensitivity to the drug ingredients; the patients with a
history of myocardial infarction, brain stroke, pregnancy or breastfeeding; the
patients do not abide by the treatment rules.
2.3. Research methods
2.3.1. Experimental research methods
- Acute toxicity study: According to the method of Litchfield - Wilcoxon,
the guidelines of the Vietnam Ministry of Health, WHO and OECD, Swiss white
mice are divided into groups with 10 mice per group. Mice in each group were
taken HVT at the dose from the highest dose (non-lethal dose) to the lowest dose
(lethal dose). Mice were completely starved for 12 hours before taking HVT (but
drunk freely). The mice were monitored the death rate in the first 72 hours as well
as their general condition for 7 days after taking the drug (including eating
activity, mental activity, walking, climbing, excretion, and so on). Died mice
were operated to evaluate the injuries of organs and then calculated LD50.

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- Semi-chronic toxicity study: According to guidelines of the Vietnam
Ministry of Health, WHO and OECD, Wistar white rats were divided into 3
groups with 10 rats per group. Rats in control group were drunk distilled water
1ml/100g/day while rats in experimental group 1 were taken low dose HVT of
11.2 g medicinal/kg (dose equivalent to the dose used on humans), and rats in
experimental group l2 were taken high-dose HVT of 33.6g medicinal/kg (3 times
higher than experimental group 1). Rats were drunk solvents and experimental
drugs for 8 weeks, once a day in the morning. After 8 weeks, the rats stopped
taking the drugs and were monitored for 2 weeks to evaluate the ability of
rehalilitation (if there was toxicity) or the causing ability of the slow toxicity of the
drug. Monitoring indicators before and during the study include general
condition, body weight, assessment of hematopoietic function, assessment of
liver and kidney function and histopathology of liver and kidney of white rats.
- Studying the effect of HVT liquid on dyslipidemia adjustment in the
model of exogenous hyperlipidemia
Rats were divided into 5 groups. Each group had 10 rats with the same
male/female ratio. All these groups were given medicine for 4 weeks as follows:
Group 1 (biological control group) was drunk distilled water 1ml/100g rat. Group
2 (model group) was drunk cholesterol oil mixture 1ml/100g, then drunk distilled
water 1ml/100g after 2 hours. Group 3 (atorvastatin group) was taken 1 ml/100g
cholesterol oil mixture, then taken atorvastatin 10 mg/kg after 2 hours. Group 4
(the 1st dosage of HVT) was taken cholesterol oil mixture 1 ml/100g, then taken
HVT dose 11.2g/kg after 2 hours. Group 5 (the 2nd dosage of HVT) was taken
cholesterol oil mixture 1 ml/100g, then taken HVT dose 33.6g / kg after 2 hours.
The rats in all groups were weighed before and after one, two and four
weeks of the experiment. Then, they were taken blood at their tails to do
quantative tests of blood lipid indices: TC, TG, HDL-C. The non-HDLcholesterol index is calculated by the formula: non-HDL-C = TC - (HDL-C).

- Model of endogenous hyperlipidemia:
The model of endogenous hyperlipidemia was adjusted by Poloxamer
407 (P-407) according to Millar et al. The 50 white mice were divided into 5
groups: Group 1 (white control group), Group 2 (model group), Group 3
(atorvastatin group), Group 4 (HVT dose of 19.2g/kg), and Group 5 (HVT dose
of 96g/kg). The mice were taken HVT, atorvastatin or distilled water within 7
days constantly before taking intraperitoneal injection P-407. After taking P-407
injection, the mice were completely starved and drunk freely. Within 24 hours
after receiving P-407, the mice were taken blood at the carotid arteries to do
quantative tests of TC, TG, HDL-C, non- HDL- C. The index of non-HDLcholeserol was calculated based on formula Non-HDL-C = (TC) – (HDL-C).
2.3.2. Clinical research methods


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- Prospective study conducted randomized, opened clinical trial with control
group, result comparison between pre-treatment and post-treatment. The 120
patients compliance with diet and exercise were devided into 2 groups as follows:
+ Group 1: The experimental group consisted of 60 patients who used HVT
liquid with 80gam/day, 2 times per day, 30 minutes after lunch and dinner.
+ Group 2: The control group consisted of 60 patients who used atorvastatin
10mg, 1 tablet per day, 1 hour after dinner.
The patients were examined, taken case history, performed hematologic
tests and taken biochemical blood tests before treatment (D0) and after 30 days of
treatment (D30). The patients were taken venous blood in the morning (without
eating anything at least 12 hours before the previous meal). Blood biochemical
tests were done afterward (TC, TG, LDL-C, HDL-C).
Evaluation of treatment results in terms of modern medicine:
+ We evaluated the change of each lipid index at the times of D0 and
D30, and compared the results of each group and between 2 groups as well.

+ The effectiveness of HVT in the patients with dyslipidemia was
evaluated by criteria as follows:
• Excellent: All blood lipid components returned to normal limits, or one
of them achieved the following changes: TC decreased by ≥ 20%, TG decreased
by ≥ 40%, HDL- C increased by ≥ 0.26mmol/l, TC-HDL-C/HDL-C (non-HDLC/HDL-C) decreased by ≥ 20%.
• Good: when achieving one of the following criteria: TC reduced by 10% 20%, TG decreased by 20% - 40%, HDL-C increased by 0.104mmol/l - 0.26
mmol/l, TC-HDL-C/HDL-C (non-HDL-C/HDL-C) decreased by 10% - 20%.
• Ineffective: Blood lipid components did not achieve the above changes.
Evaluation of treatment results in terms of traditional medicine
+ The effectiveness of HVT was evaluated through the methods of
inspection, inquiry and palpation.
+ The effectiveness of HVT in the patients with dyslipidemia was
evaluated by criteria as follows:
• Excellent: There were significant improvements in clinical symptoms
with the total decreased score ≥ 70%.
• Good: There were small changes in clinical symptoms with the total
decreased score ≥ 30%.
• Ineffective: The total decreased score of clinical symptoms was less than
30%.
Evaluation of unwanted effects of HVT
Clinical evaluation: Some symptoms such as abdominal pain, nausea,
rash, diarrhea, muscle pain, etc were evaluated.


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Sub-clinical evaluation: The results of hematological test and blood
biochemical tests before and after treatment were used as good indicators to
assess.
Data analysis: The data was collected and analyzed by the method and

Biomedical statistical algorithm of STATA 14.0.
Research Ethics: The study was approved by the Medical Council of
Traditional Medicine Hospital, Ministry of Public Security. The patients, who
voluntarily participated in the study, were performed tests and given treatment
without paying any fee. All information was kept confidential and only general
results were allowed to publish.
Chapter 3. RESEARCH RESULTS
3.1. Acute toxicity and sub-chronic toxicity of HVT liquid drug
3.1.1. Acute toxicity
White mice were taken HVT by increasing doses from the lowest to the
highest dose with 600.0g medicinal/kg/24 hours (up to 31.25 times higher than
the equivalent dose on the human) but there were no abnormal signs within 7
day follow-up and no mice died within 72 hours after taking the sample drug.
Therefore, the acute toxicity of LD50 of HVT has not been determined by oral
administration.
3.1.2. Sub-chronic toxicity
* General condition: During the experiment, the rats in all 3 groups were
operating normally with bright eyes, smooth hair, good eating, dry feces. There were
no particular manifestations in these three groups of rats during the study period.
* Changes in body weight of rats: At 4-8 weeks after taking the sample
drugs and 2 weeks after stopping the drugs, the weight of rats in all 3 groups were
documented to be increased compared to the weight before the study. There was
no difference in the level of weight gain of the rats between the control group and
the experimental group (p> 0.05).
* The effect of HVT on the mice’s blood lipid index
Table 3.1. The effect of HVT on the number of rat’s red blood cells
Time
Before taking
drugs
4 weeks after

taking drugs

The number of red blood cells (T/l)
The group 1
The group 2
The control
(n=10) (2)
(n=10) (3)
group (n=10) (1)

p2-1, p3-1,
p3-2

8,49 ± 0,56

8,27 ± 0,34

8,32 ± 0,55

>0,05

8,54 ± 0,93

8,59 ± 0,45

8,44 ± 0,72

>0,05

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8 weeks after
taking drugs
2 weeks after
stopping drugs
P(before-after)

8,92 ± 0,68

8,72± 0,73

8,63 ± 0,58

>0,05

8,70 ± 0,69

8,48 ± 1,41

8,82 ± 0,68

>0,05

> 0,05

> 0,05

> 0,05

Table 3.2. The effect of HVT on the concentration of hemoglobin in rat

blood
Times
Before taking
drugs
4 weeks after
taking drugs
8 weeks after
taking drugs
2 weeks after
stopping drugs
P(before-after)

The concentration of hemoglobin (g/dl )
The group 1
The group 2
The control
(n=10) (2)
(n=10) (3)
group (n=10) (1)

p2-1, p3-1,
p3-2

15,32 ± 0,65

15,37 ± 0,76

15,19 ± 0,83

>0,05

14,46 ± 1,25

15,30 ± 0,74

15,12 ± 0,96

>0,05

15,43 ± 0,83

15,38 ± 1,13

14,40 ± 0,98

>0,05

16,48 ± 0,97

16,27 ± 1,00

16,37 ± 2,62

>0,05

> 0,05

> 0,05

> 0,05

Table 3.3. The effect of HVT on the number of rat’s white blood cells
Time
Before taking
drugs
4 weeks after
taking drugs
8 weeks after
taking drugs
2 weeks after
stopping drugs
P(before-after)

The number of white blood cells (G/l)
The control
The group 1
The group 2
group (n=10) (1)
(n=10) (2)
(n=10) (3)

p2-1, p31, p3-2

5,12 ± 1,48

4,53 ± 0,80

4,73 ± 1,57

>0,05

5,69 ± 1,41

4,96± 1,22

5,33 ± 1,52

>0,05

5,23 ± 1,30

4,65 ± 1,14

4,90 ± 1,40

>0,05

5,67 ± 0,82

4,90 ± 0,62

5,57 ± 1,50

>0,05

> 0,05

> 0,05

> 0,05

Table 3.4. The effect of HVT on the number of thrombocytes in rat blood


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Times
Before taking
drugs
4 weeks after
taking drugs
8 weeks after
taking drugs
2 weeks after
stopping drugs
P(before-after)

The number of thrombocytes (G/l)
The group 1
The group 2
The control group
(n=10) (1)
(n=10) (2)
(n=10) (3)

p2-1, p3-1,
p3-2

472,5 ± 66,9

478,3 ± 46,6

483,5 ± 131,2

>0,05

418,5 ± 89,2

445,5 ± 66,6

449,1 ± 104,9

>0,05

428,5 ± 36,1

439,2 ± 69,3

443,1 ± 85,9

>0,05

458,2 ± 11,9

433,3 ± 41,1

453,6 ± 118,1

>0,05

> 0,05

> 0,05

> 0,05

After 4 - 8 weeks of taking HVT and after 2 weeks of stopping HVT, the
number of red bloods cells, white blood cells, thrombocytes and the hemoglobin
concentration in both of the experimental group 1 (low HVT doses) and the
experimental group 2 (high HVT doses) did not change in comparision to the time
before taking the sample drugs and to the control group (p> 0.05).
* Evaluation of liver function
Table 3.5. The effect of HVT on the activity of AST (GOT) in rat blood
Times
Before taking
drugs
4 weeks after
taking drugs
8 weeks after
taking drugs
2 weeks after
stopping drugs
P(before-after)

The activity of AST (UI/l)
The control
The group 1
The group 2
group (n=10) (1)
(n=10) (2)

(n=10) (3)

p2-1, p3-1,
p3-2

105,60 ± 9,58

108,90 ± 14,00

112,90 ± 14,32

>0,05

119,60 ± 22,74

117,50 ± 17,53

118,90 ± 23,65

>0,05

113,80 ± 18,27

112,60 ± 14,50

108,70 ± 11,21

>0,05

111,00 ± 14,20

103,14 ± 5,96

108,14 ± 19,78

>0,05

> 0,05

> 0,05

> 0,05

Table 3.6. The effect of HVT on the activity of ALT (GPT) in rat blood
Times
Before taking

The activity of ALT (UI/l)
The control
The group 1
The group 2
group (n=10) (1)
(n=10) (2)
(n=10) (3)
57,30 ± 5,33
61,70 ± 4,76
61,60 ± 7,26

p2-1, p3-1,
p3-2

>0,05


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drugs
4 weeks after
taking drugs
8 weeks after
taking drugs
2 weeks after
stopping drugs
P(before-after)

62,80 ± 14,47

60,20 ± 9,10

60,10 ± 9,26

>0,05

59,30 ± 7,10

59,20 ± 6,78

59,90 ± 6,10

>0,05

57,00 ± 5,44

56,71 ± 4,72

52,71 ± 9,62

>0,05

> 0,05

> 0,05

> 0,05

After 4 - 8 weeks of taking HVT and after 2 weeks of stopping HVT, there
was not any statistically significant difference in the activities of AST and ALT in
rat blood in both of the experimental group 1 (low HVT dose) and the experimental
group 2 (high HVT dose), in comparison to the control group and between the two
times before and after taking the sample drugs (p> 0.05).
* Evaluation of kidney function
Table 3.7. The effect of HVT on the concentration of creatinine in rat blood
Times
Before taking drugs
4 weeks after taking
drugs
8 weeks after taking
drugs
2 weeks after
stopping drugs
P(before-after)

The concentration of Creatinine (mg/dl)
The group 1
The group 2
The control
(n=10) (2)
(n=10) (3)
group (n=10) (1)
1,06 ± 0,05
1,06 ± 0,05
1,07 ± 0,05

p2-1, p3-1,
p3-2

>0,05

1,04 ± 0,05

1,05 ± 0,05

1,03 ± 0,05

>0,05

1,05 ± 0,05

1,05 ± 0,05

1,05 ± 0,05

>0,05

1,03 ± 0,08

1,04 ± 0,05

1,04 ± 0,10

>0,05

> 0,05

> 0,05

> 0,05

After 4 - 8 weeks of taking HVT and after 2 weeks of stopping HVT, there
was not any statistically significant difference in the concentration of creatinine in
both of the experimental group 1 (low HVT dose) and the experimental group 2
(high HVT dose), in comparison to the control group and between the two times
before and after taking the sample drugs (p> 0.05).
3.2. The pharmacological effect of HVT in experiment study
Table 3.8. The lipid index at the time after 4 weeks of experiment in
exogenous model (n=10)
Groups
Group 1 : The

The concentration of blood lipid indices
TC

TG
HDL - C
Non-HDL - C
2,29  0,07
0,77  0,02 0,81  0,03
1,48  0,08


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biological control
group
Group 2 : The
model group
Group 3:
Atorvastatin
group
Group 4: The 1st
dose of HVT
(11,2 g/kg)
Group 5 : The
2nd dose of HVT
(33,6 g/kg)

4,65 
0,21***

0,93 
0,04**

1,76 

0,05***

2,89  0,2***

3,33 
0,18***

0,85  0,04

1,58 0,09

1,75  0,18**

2,92 
0,09***

0,87  0,03

1,49 
0,05**

1,43 
0,11***

2,96 
0,11***

0,89  0,03

1,55 

0,04**

1,41 
0,11***

Notes: The differences in comparison to the model group: *: p < 0,05; **: p<0,01;
***: p < 0,001.
There was a significant decrease in the concentration of TC and non-HDLC in in both doses of 11.2 g/kg and 33.6 g/kg, in comparison to the model group (p
<0.001). The effect of 2 doses of HVT was similar and equivalent to atorvastatin 10
mg / kg (p> 0.05). There was no statistically significant difference in the
concentration of blood lipid index between the atorvastatin group and two HVT
doses at the time after 4 weeks of experiment (p> 0.05).
Table 3.9. Blood lipid index after the experiment in
endogenous model (n = 10)
Groups
Group 2:
The model
group
Group 3:
Atorvastatin
group
Group 4:
HVT
19,2g/kg
Group 5:
HVT
96,0g/kg

TC

TG

HDL-C

Non-HDL-C

6,31 ± 1,60

9,01 ± 2,36

2,11 ± 0,17

4,20 ± 1,68

4,15 ±
0,93**
(↓ 34,2%)

8,16 ± 2,65
(↓ 9,4%)

2,02 ± 0,12

2,13 ±
0,94**
(↓ 49,3%)

5,89 ± 1,37
(↓ 6,7%)

8,69 ± 3,90
(↓ 3,6%)

2,78 ± 0,38***
(↑ 31,8%)

3,12 ± 1,37
(↓ 25,7%)

4,91 ± 0,51 *
(↓ 22,2%)

5,74 ± 1,79**
(↓ 36,3%)

2,88 ± 0,48***
(↑ 36,5%)

2,03 ±
0,89**
(↓ 51,7%)


13

Notes: The difference in comparison to the model group: *: p < 0,05; **: p<0,01;
***: p < 0,001.
There was a significant increase in the concentration of HDL-C in the group
of HVT dose of 19.2g/kg in comparison to the model group, with statistical
significance (p <0.001). This effect was stronger than the atorvastatin group of 100

mg/kg.
There was a significant decrease in the indices of TC, TG, and non-HDL-C
in the HVT dose of 96.0 g/kg in comparison to the model group (p<0,05, p < 0,01
and p < 0,01). The HVT made a significant increase in the concentration of HDL-C
in comparison to the model group. This effect was stronger than the atorvastatin
group of 100 mg /kg (p<0,001).
3.3. The effect of HVT in the patients with dyslipidemia caused by
internal phlegm-dampness
3.3.1. The effect of HVT through sub-clinical indices
Table 3.10. The changes of the sub-clinical indices after treatment
Times

D0

D30

Changes

p

HVT

6,22  0,48

↓15,8%

Atorvastatin

6,37  0,72

<0,00
1
<0,00
1

p
HVT

> 0,05
2,45  1,13

Atorvastatin
p
HVT

2,571,25
> 0,05

5,24 
0,48
5,20 
0,76
> 0,05
1,94 
0,60
2,130,95
> 0,05
1,37 
0,30
1,48 

0,26
> 0,05
2,99 
0,51
2,88 
0,80
> 0,05
3,87 
0,52
3,72 

Indices
TC

TG

HDLC

LDLC
NonHDLC

1,17  0,32

Atorvastatin

1,28  0,34

p
HVT

> 0,05
3,93  0,64

Atorvastatin

3,91  0,74

p
HVT

> 0,05
5,05  0,51

Atorvastatin

5,09  0,66

↓18,4%
↓20,8%
↓17,1%
↑17,1%
↑15,6%
↓23,9%
↓26,3%
↓23,4%
↓26,9%

<0,00
1
<0,01

<0,00
1
<0,00
1
<0,00
1
<0,00
1
<0,00
1
<0,00


14

p

> 0,05

0,73
> 0,05

1

After 30 days of treatment, the concentration of TC, TG, LDL-C, nonHDL-C decreased significantly in both groups compared to the time before
treatment. The difference at the time before and after treatment of 2 groups was
statistically significant. The difference in the degree of reduction in the sub-clinical
indices between the two groups was not statistically significant (p> 0.05).
The concentration of HDL-C increased markedly in both groups compared
to the time before treatment. The difference at the time before and after treatment of

2 groups was statistically significant (p <0.001). The difference in the increasing
level of HDL-C between the two groups was not statistically significant (p> 0.05).
* Evaluation of treatment results in terms of modern medicine
60.0

51.7

Tốt

45.0 43.3

43.3

Khá

40.0

11.7 Không

5.0

20.0

hiệu quả

0.0
HVT

Atorvastatin

Diagram 3.1. Evaluation of the treatment effect in
terms of modern medicine
In terms of modern medicine, the treatment effect in HVT group was shown
as follows: excellent percentage was 51.7%, good percentage was 43.3% and
ineffective percentage was 5%. The Atorvastatin group has achieved excellent result
with 45.0%, good result with 43.3%, and ineffective result with 11.7%. The
difference between the two groups was not statistically significant (p> 0.05).
Table 3.11. The changes in risk assessment indices of
atherosclerosis after treatment
Times
D0
D30
Changes
p
Indices
AI
HVT
2,98

↓35,50%
<0,001
4,62  1,30
Atorvastatin

4,22  1,11

0,85
2,59 
0,69

↓38,6%

<0,001


15

CRI

p
HVT

> 0,05
5,62  1,30

Atorvastatin

5,22  1,11

p
HVT

AIP

> 0,05
0,66  0,11

Atorvastatin

0,62  0,10

p

> 0,05

> 0,05
3,98 
0,85
3,59 
0,69
> 0,05
0,22 
0,24
0,19 
0,26
> 0,05

↓29,2%

<0,001

↓31,2%

<0,001

↓67,1%

<0,001

↓69,3%

<0,001

After 30 days of treatment, the indices of AI (TC-HDL-C / HDL-C), CRI
(TC / HDL-C) and AIP (log (TG / HDL-C)) has been decreased markedly in both
group compared to the time before treatment. The difference at the time before and
after treatment of 2 groups was statistically significant (p <0.001). The difference in
decreasing level of AI, CRI and AIP indices of the two groups was not statistically
significant (p> 0.05).
3.3.2. The effect of HVT on some clinical indicators
Table 3.12. The changes of clinical symptoms in
terms of inspection
Groups
Inspection
Fatty body
Thick & teethmarked tongue
White & slimy
fur tongue

HVT
D0
(n %)
16
(26,7)
41
(68,3)
39
(65,0)

D30

(n %)
12
(20,0)
12
(20,0)
15
(25,0)

Atorvastatin
D0
D30
(n %)
(n %)
11
10
(18,3) (16,7)
46
24
(76,7) (40,0)
38
11
(63,3) (18,3)

Total
D0
D30
(n %)
(n %)
27
22

(22,5) (18,3)
87
36
(72,5) (30,0)
77
26
(64,2) (21,7)

After treatment, the number of patients with fatty condition was decreased
by 22 patients (18.3%) compared to 27 (22.5%) before treatment. The number of
patients with thick & teeth-marked tongue was reduced by 36 (30.0%) after treatment
in comparison to 87 patients (72.5%) before treatment. There was also a significant
reduction in the number of patients with white & slimy fur tongue before and after
treatment (77 patients (64.2%) compare to 26 patients (21.7%)).
Table 3.13. The changes of pulse in terms of traditional medicine
Groups

HVT

Atorvastatin

Total


16
D30
D0
(n %)
(n %)
Pulpation

Moderate
&
0 (0,0) 23 (38,3)
soggy pulse
Sunken pulse
0 (0)
11 (18,3)
String-like pulse 10 (16,7) 7 (11,7)
Slippery pulse
21 (35,0) 10 (16,7)
Slippery & string29 (48,3) 9 (15,0)
like pulse

D0
(n %)

D30
(n %)

0 (0)

14 (23,3)

D0
(n %)

D30
(n %)

0 (0,0) 37 (30,8)

0 (0,0)
11 (18,3)
23 (38,3)

9 (15,0) 0 (0,0) 20 (16,7)
8 (13,3) 21 (17,5) 15 (12,5)
13 (21,7) 44 (36,7) 23 (19,2)

26 (43,4)

16 (26,7) 55 (45,8) 25 (20,8)

The number of patients with slippery & string-like pulse in the HVT
group was significantly decreased after treatment (9 patients (15.0%) compared
to 29 patients (48.3%)). The number of patients with slippery & string-like pulse
in the atorvastatin group was also reduced after treatment (16 patients (26.7%)
compared to 26 patients (43.4%)). There were 21 patients with slippery pulse
before treatment, however, after receiving HVT treatment, the number of patients
with slippery pulse was also significantly reduced by 10 patients (16.7%). In the
Atorvastatin group, there were 13 patients (21.7%) after treatment compared to
23 patients (38.3%) before treatment.
Table 3.14. The changes of clinical symptoms in terms of inquiry
Groups
Symptoms
Headache

Dizziness

Numbness

in limbs
Insomnia

No pain
Mild
Moderate
Severe
No pain
Mild
Moderate
Severe
No pain
Mild
Moderate
Severe
No pain
Mild

HVT

Atorvastatin

Total

D0 (n %)

D30 (n %)

D0 (n %)

D30 (n %) D0 (n %) D30 (n %)

9 (15,0)
3 (5,0)
18 (30,0)
30 (50,0)
2 (3,3)
3 (5,0)
26 (43,3)
29 (48,3)
10 (16,7)
11 (18,3)
22 (36,7)
17 (28,3)
1 (1,7)
8 (13,3)

30 (50,0)
30 (50,0)
0 (0)
0 (0)
27 (45,0)
33 (55,0)
0 (0)
0 (0)
22 (36,7)
38 (63,3)
0 (0)
0 (0)
12 (20,0)

43 (71,7)

0 (0)
0 (0)
29 (48,3)
31 (51,7)
0 (0)
4 (6,7)
40 (66,7)
16 (26,7)
8 (13,3)
11 (18,3)
31 (51,7)
10 (16,7)
10 (16,7)
10 (16,7)

14 (23,3)
41 (68,3)
5(8,3)
0 (0)
13 (21,7)
43 (71,7)
4 (6,7)
0 (0)
11 (18,3)
47 (78,3)
2 (3,3)
0 (0)
19 (31,7)

38 (63,3)

9 (7,5)
3 (2,5)
47 (39,2)
61 (50,8)
2 (1,7)
7 (5,8)
66 (55,0)
45 (37,5)
18(15,0)
22 (18,3)
53 (44,2)
27 (22,5)
11 (9,2)
18 (15,0)

44 (36,7)
71 (59,2)
5 (4,2)
0 (0)
40 (33,3)
76 (63,3)
4 (3,3)
0 (0)
33 (27,5)
85 (70,8)
2 (1,7)
0 (0)
31 (25,8)

81 (67,5)


17
Moderate 45 (75,0)
Severe 6 (10,0)

5 (8,3)
0 (0)

39 (65,0)
1 (1,7)

3 (5,0)
0 (0)

84 (70,0)
7 (5,8)

8 (6,7)
0 (0)

In both groups, some symptoms caused by phlegm-dampness such as
severe headaches, dizziness, numbness in limbs, insomnia have been
significantly improved after treatment compared to them before treatment. The
difference before and after treatment in both groups was statistically significant
(p <0.05).
* Evaluation of the treatment results in terms of traditional medicine
100.0
80.0

60.0
40.0
20.0
0.0

Tốt

85.0
61.7

Khá

38.3
0.0
HVT

10.0

5.0

Không
hiệu quả

Atorvastatin

Diagram 3.2. Evaluation of the treatment effect in terms of
traditional medicine
The effectiveness of treatment according to traditional medicine in the HVT
group achieved excellent results with 38.3% and good results with 61.7%. There
was not any patient who was ineffective to the treatment. The Atorvastatin group

achieved excellent results with 10%, good results with 85%, and ineffective results
with 5%. The difference between the two groups was statistically significant (p
<0.05).
3.3.3. Evaluation of unwanted effects
No unwanted effects have been found in the clinical study.
Chapter 4. DISCUSSIONS
4.1. Acute toxicity and semi-chronic toxicity of HVT liquid drug
4.1.1. Acute toxicity
White mice were taken HVT with the increasing dose from 360.0g/kg/24
hours to 600.0g/kg/24 hours (31.25 times higher than the dose used in human).
After taking the sample drug, no mice died and no abnormal manifestation were
observed in mice. Therefore, acute toxicity and LD 50 of HVT have not been
determined.


18

4.1.2. Semi-toxic toxicity
After 8 weeks of taking the medicine and after 2 weeks of stopping the drug
on rats, the results showed that HVT with dose of 11.2g/kg and 33.6g/kg did not
affect the development of rats, and there were no changes observed in the indicators
of hematology, blood biochemistry and general images, histopathology of liver and
kidney in rats. Therefore, HVT has not shown a semi-chronic toxicity of white rats
by oral administration.
4.2. The pharmacological effects of HVT in the
experimental study
4.2.2. The model of exogenous dyslipidemia
Both HVT doses have showed a significant lipid-lowering effect after 4
weeks of study. This was expressed by a statistically significant reduction in the
concentration of TC and non-HDL-C compared to the model group (p <0.001).

This effect was equivalent to the atorvastatin group at 10 mg/kg/day (p> 0.05).
Lipid-lowering effects of low-dose HVT were not statistically significantly different
from high-dose HVT and this was equivalent to the atorvastatin group at 10mg/kg/
day. Therefore, HVT has shown the good effect of adjusting dyslipidemia on the
model of exogenous dyslipidemia. This effect did not depend on whichever highdose or low-dose HVT (p> 0.05).
4.2.2. The model of endogenous dyslipidemia
The indices of TC, TG, non-HDL-C in the mice’s serum of the group
taking HVT dose of 19.2g/kg/day tended to decrease compared to the model group.
There was a statistically significant reduction in the group taking HVT dose of
96.0g/kg/day. The TC-lowering effect of high-dose HVT was lower than that of the
atorvastatin at a dose of 100 mg/kg (22.2% compared to 34.2%), however the TGlowering effect was significantly higher than that of the atorvastatin (36.3%
compared to 9.4%). In this study, HVT at both doses has showed a significant
increase in HDL-C, better than the atorvastatin group (p <0.001). From these
results, HVT has shown the good effect of adjusting dyslipidemia on the model
endogenous dyslipidemia by P-407. This effect did not depend on whichever HVT
high-dose or low-dose.
Thus, HVT has shown the effect of adjusting dyslipidemia on both models
of endogenous and exogenous dyslipidemia. Based on published studies, there are
quite a number of lipid-lowering mechanisms that can partly explain the effect of
dyslipidemia adjustment of the HVT remedy.


19

The polymethoxyflavon components in Pericarpium Citri reticulatae
perenne have been shown to inhibit the ability of pancreatic lipase, in which
nobiletine has been proved to be the strongest lipase inhibitor. In the hamsters with
hypercholesterolemia by diet, polymethoxylated flavones (mainly tangeretin) and
glucosid flavanone (hesperidin and naringin) in Pericarpium Citri reticulatae
perenne have been shown to decrease the concentration of VLDL and LDL, or

tend to reduce triacylglycerol in serum.
The lipid-lowering effect of Folium Nelumbinis nuciferae has been
documented in several studies. The study by Lee et al. (2010) showed that rabbits
fed a high-fat diet supplemented with the liquid extract from Folium Nelumbinis
nuciferae at a ratio of 0.5% and 1% had a significant decrease in the concentration
of TG (30% and 46.6%) and LDL (45.4 and 45.9%) compared to the rabbits that
only fed a fatty diet.
Cleistocalyx operculatus Roxb is often commonly used to be one of the
Vietnamese tea drinking. In vitro, the extract from Cleistocalyx operculatus Roxb
with the high content of phenol and flavonoids has showed to be the most effective
inhibitor on lipase when compared to the extract from green tea and guava leaves.
Besides the effect of blood glucose reduction, the extract from Cleistocalyx
operculatus Roxb also showed the significant reduction in the concentration of TC
and TG in serum when the rats with treptozotocin-induced diabetes were orally
administered the sample for 8 weeks (500 mg/kg day). Catechin is also a rich
ingredient in Cleistocalyx operculatus Roxb, therefore, the lipid-lowering
mechanism of Cleistocalyx operculatus Roxb may also be related to the change of
gene manifestations caused by lipid metabolism.
4.3. Evaluation of the effect of HVT in the patients with dyslipidemia caused
by internal phlegm-dampness
4.3.1. The effect of HVT through some clinical indicators
* The change of TC concentration
After 30 days of treatment, the concentration of TC was significantly
reduced in both groups compared to it before treatment. There was a statistical
significant difference between the two groups before and after treatment (p <0.001).
The difference in the TC reduction between the two groups was not statistically
significant (p> 0.05). According to Goode GK et al., who analyzed 35 large-scale
studies on 77.257 patients who were monitored from 2 to 12 years, has concluded
that if there is the reduction in TC by 20%, the mortality will reduce by 18.1% in

20

general and 24.1% in the patients with coronary artery disease. Thus, how to reduce
the concentration of TC is one of the top goals in dyslipidemia treatment.
The decrease in TC concentration of HVT is also relevant to the results of
TC lowering effect on the model of exogenous hyperlipidemia in our study.
* The change of TG concentration
The concentration of blood TG is a key indicator to explore the body's lipid
balance and contribute to reflecting the risks of atherosclerosis.
After 30 days of treatment, the concentration of TG was significantly
decreased in both groups compared to it before treatment. There was a statistical
significant difference between the two groups before and after treatment (p <0.001).
The difference in the TG reduction between the two groups was not statistically
significant (p > 0.05).
* The change of HDL-C concentration
After 30 days of treatment, the concentration of HDL-C was significantly
increased in both groups compared to it before treatment. There was a statistical
significant difference between the two groups before and after treatment (p <0.001).
The difference in the HDL-C increase between the two groups was not statistically
significant (p > 0.05).
HDL-C acts to transport excessive TC from the peripheral to the liver,
where TC is degraded and eliminated by the bile-duct, thus HDL-C is also called
good cholesterol. Reducing HDL-C will contribute to increasing the risk of
cardiovascular disease. Therefore, many authors consider increasing HDL-C levels
as one of the important treatment targets. The increase in HDL-C concentration of
this study is also very relevant to the research results of pharmacological effects of
HVT on the model of endogenous hyperlipidemia (There was a statistically
significant increase in HDL-C at both doses of HVT (p <0.001), and the HDL-C
increase of HVT groups was much higher than that of the atorvastatin group (p

<0.001)).
* The change of LDL-C concentration
After 30 days of treatment, the concentration of LDL-C was significantly
reduced in both groups compared to it before treatment. There was a statistical
significant difference between the two groups before and after treatment (p <0.001).
The difference in the LDL-C decrease between the two groups was not statistically
significant (p > 0.05).
Contrary to HDL-C, LDL-C is also known as bad cholesterol. TC causes


21

atherosclerosis because it has the ability to transport TC in the blood to peripheral
cells. The higher the LDL-C concentration is, the higher the risks of atherosclerosis
are. Therefore, how to reduce LDL-C is the first target of treatment for
dyslipidemia.
* The change of non-HDL-C concentration
After 30 days of treatment, the concentration of non-HDL-C was
significantly reduced in both groups compared to it before treatment. There was a
statistical significant difference between the two groups before and after treatment
(p <0.001). The difference in the non-HDL-C decrease between the two groups
was not statistically significant (p > 0.05).
Non-HDL-C is the total cholesterol of apoB-containing lipoprotein
particles, which are potential to cause atherosclerosis. There are more evidences
relevant to the viewpoint that the non-HDL-C is associated with cardiovascular
disease than LDL-C is. This relationship is significantly expressed in those with
increased and non-increased TG concentration.
According to the ATP III guidelines, LDL-C reduction is the most
important treatment target, following by TG and non-HDL-C.
Thus, the reduction of non-HDL-C is one of the important goals of

dyslipidemia treatment. The clinical results of non-HDL-C reduction of HVT were
also relevant to the results of non-HDL-C reduction in the model of exogenous and
endogenous hyperlipidemia in our study.
* Evaluation of the treatment results in terms of modern medicine
In terms of modern medicine, the treatment effect in HVT group was
shown as follows: excellent percentage was 51.7%, good percentage was 43.3%
and ineffective percentage was 5%. The Atorvastatin group has achieved excellent
result with 45.0%, good result with 43.3%, and ineffective result with 11.7%. The
difference between the two groups was not statistically significant (p> 0.05). This
result has showed a significant reduction in blood lipid components of the HVT
remedy.
* The results of changing indcators of atherosclerosis risks
AI index (AI = TC-HDL-C / HDL-C) was used to evaluate the risk of
atherosclerosis. This indicator has showed that if the concentration of HDL-C
increases, and/or the concentration of TC decreases, the AI index will decrease
accordingly.
CRI (CRI = TC/HDL-C) was used to evaluate the risk of coronary. This


22

indicator has showed that if the concentration of HDL-C increases, and/or the
concentration of TC decreases, the CRI will decrease accordingly.
In recent years, researchers have been focusing on a new comprehensive
lipid index, called plasma atherosclerosis index AIP = log (TG/HDL-C), which can
reflect the balance among the factors causing atherosclerosis and atherosclerosis.
After 30 days of treatment, the indices of AI, CRI and AIP were
significantly decreased in both groups compared to them before treatment. There
was a statistical significant difference between the two groups before and after
treatment (p <0.001). The difference in the reduction of the above indices between

the two groups was not statistically significant (p> 0.05). Thus, the effect of HVT in
reducing AI, CRI and AIP is equivalent to the effect of atorvastatin.
4.3.2. The effect of HVT through some clinical symptoms
* The results of changing some functional symptoms
Some symptoms of internal phlegm-dampness such as fatty body, thick &
teeth-marked tongue, white & slimy fur tongue, slippery & string-like pulse,
headache, dizziness, numbness in limbs, insomnia have been significantly
improved in the patients in both groups after treatment, compared to them before
treatment (p <0.05). There was a statistical significant difference between the two
groups before and after treatment (p < 0.05). In other words, the improvement of
clinical symptoms in the HVT group was better than that of the atorvastatin group.
We have focused on analyzing some of the following main symptoms:
+ At the time of D0, the symptoms of moderate and severe headache at the
HVT group were 48/60 patients, accounting for 80%. At the time of D 30 after 30
days of treatment, there were no patients with moderate and severe headache, but
only 30 patients with mild headache, accounting for 50%.
+ At the time of D0, the symptoms of moderate and severe headache at the
atorvastatin group were 60/60 patients, accounting for 100%. At the time of D30
after 30 days of treatment, there was 5 patients with moderate headache and 41
patients with mild headache, accounting for 74.6%.
In the manifestation of atherosclerosis, because this is an especially sensitive
organ with lack of oxygen, so anemia has the earliest symptoms. At the first stage,
the patients are suffered from headache, dizziness, tinnitus; and then, memory
disorders and forgetfulness are reported symptoms at the later stage. In our study,
the symptoms of headache and dizziness have been improved markedly after 30
days of treatment.


23

From traditional medicine point of view, head pain is also referred to as
headache partern due to the phlegm turbidity obstructing the upward movement of
clearing yang caused pain in head.
Dizziness is a symptom belonging to the dizziness pattern. Chu Dan Khe
said that “Without phlegm, there is no dizziness pattern”.
When the main symptoms such as headache, dizziness have been improved, the
symptoms of insomnia have also been relieved.
Therefore, the improvement of the above symptoms is one of the factors
that demonstrate the appropriateness of the HVT remedy in the treatment of the
patients with internal phlegm-dampness.
* Evaluation of the treatment results in terms of traditional medicine
In terms of traditional medicine, the effectiveness of treatment in the HVT
group achieved excellent results with 38.3% and good results with 61.7%. There
was not any patient who was ineffective to the treatment. The atorvastatin group
achieved excellent results with 10%, good results with 85%, and ineffective results
with 5%. The difference between the two groups was statistically significant (p
<0.05). This suggests a significant reduction in the functional symptoms of the
HVT remedy, compared to the effect of the atorvastatin at 10mg/day. The effect of
HVT is better than the atorvastatin group in reducing some functional symptoms in
the patients with dyslipidemia such as fatty condition, thick & teeth-marked tongue,
white & slimy fur tongue, slippery & string-like pulse, headache, dizziness,
numbness in limbs, insomnia. To explain for this result, we assume that the above
symptoms are typical manifestations caused by internal phlegm-dampness that the
HVT remedy is very suitable for treatment of dyslipidemia by fortifying spleen,
regulating qi, resolving phlegm, relieving dampness. The three medicinal herbs that
made up the HVT remedy have also been proven to be effective in lipid lowering,
antioxidant, and diabetes treatment by pharmacological studies of modern
medicine.
4.3.3. Evaluation of the unwanted effect
No unwanted effects have been found in HVT remedy in clinical study.

CONCLUSIONS
1. Acute toxicity and semi-chronic toxicity of HVT liquid drug
Although white mice were taken HVT with the highest dose of
600.0g/kg/24 hours (31.25 times higher than the dose used in human), no mice died
and no abnormal manifestation were observed. Therefore, acute toxicity and LD50


24

of HVT have not been determined by orally administration.
HVT did not cause semi-chronic toxicity in rats when they were
administered the dose of 11.2g/kg/day (equivalent to human therapeutic dose) and
the dose of 33.6g/kg/day (3 times higher than the dose on humans) in 8 successive
weeks and after 2 weeks stopping the drug. The General condition, weight,
hematopoietic function, liver function, degree of liver cell destruction, renal function
and histopathology of liver and kidney were all within normal limits. There was no
statistical significant difference compared to the control group.
2. HVT has the effect of dyslipidemia adjustment in the model of exogenous
and endogenous hyperlipidemia
In the model of exogenous hyperlipidemia, HVT at both doses of 11.2 g/kg/
day (equivalent to human therapeutic dose) and 33.6 g/kg/day all reduced the
indices of TC and non-HDL-C at the times after 2 weeks and 4 weeks taking the
sample drug. This effect is the same in 2 doses and equivalent to the atorvastatin
dose (100mg/kg/day).
In the model of endogenous hyperlipidemia, HVT at both doses of
19.2g/kg/day (equivalent to human therapeutic dose) and 96g/kg/day all increased
the index of HDL-C. This effect is the same in 2 doses and better than atorvastatin
dose of 100mg/kg/day. The reduction of TC of high HVT dose (96g/kg/day) is
lower than the atorvastatin dose but the reduction of TG is better than the
atorvastatin dose (100mg/kg/day). Thus, the lowering effect of TG and non-HDLC, the increasing effect of HDL-C at high HVT dose are all better than the effect of

the atorvastatin dose (100mg/g/day).
3. HVT has the effect of dyslipidemia adjustment in clinical study
- After 30 days of treatment for 60 patients with dyslipidemia caused by
internal phlegm-dampness, HVT dose 80g/day was proven to reduce the
concentration of TC (15.8%), TG (20.8%), LDL-C (23.9%), non-HDL-C (23.4%)
and to increase the concentration of HDL-C (17.1%) compared to them before
treatment. The indices of AI, CRI and AIP were decreased by 35.5, 29.2% and
67.1% respectively. These effects were equivalent to the atorvastatin dose
(10mg/day).
- In terms of modern medicine, the results of HVT are ranked as follows:
excellent (51.7%), good (43.3%) and ineffective (5%).
- In terms of traditional medicine, the results of HVT are ranked as follows:
excellent (38.3%), good (61.7%) and ineffective (0%).


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- HVT is safe for treatment and there are no unwanted effects in clinical
study.
RECOMMENDATIONS
From the results of the dessertation, we would like to make the following
recommendations:
- HVT not only acts to significantly improve the index of blood lipid in the
patients with dyslipidemia, but also be safe for treatment. Therefore, clinical studies
should be expanded with a larger number of patients, longer duration of treatment
for more comprehensive results.
- A study on the effect of atherosclerosis decrease of HVT in both
experimental and clinical models should be implemented.
- It is advisable to study how to transfer HSN from liquid form into easy-touse capsules for patients, and to extend expiration date.