1
INTRODUCTION
In recent years, along with the development of economy, social
life, the diet has become increasingly rich and unreasonable, causing
an increase in dyslipidemia. Regardless the fact that it is not an acute
disease, dyslipidemia is one of the leading risk factors which cause
formation and development of atherosclerosis. In Vietnam,
atherosclerotic disease with clinical manifestations such as coronary
insufficiency, myocardial infarction, cerebral vascular accident, etc.
currently tends to increase rapidly according to the pace of social
development. With modern equipment, researchers have proved that
treating dyslipidemia is not only limits the progression of atheroma
but also stabilizes the plaque to prevent high fatal complications.
Modern medicine has found and used many drugs in different groups
such as statins, fibrates, resin, etc. These drugs have the effect of
adjusting dyslipidemia at different levels but have side effects, such
as digestive disorders, muscle pain, increase of liver enzymes, etc.
The “Ha mo mau” remedy was rooted from the “Nhi Tran” formula
with 2 additional ingredients. The ingredients include: Pericarpium
Citri Reticulatae perenne, Rhizoma Pinelliae, Poria Cocos, Radix
Glycyrrhizae, Radix Achyranthes bidentatae, and Rhizoma Alocaciae
odorae. The remedy has the effect of potentially eliminating the
sputum, rheumatism, lowering the blood pressure. The remedy is
produced in the form of melted granules.
The objectives of the research:
1. To study the acute toxicity and semi-chronic toxicity of “Ha mo
mau” granules in the experiment.
2. To assess the effect of reducing the dyslipidemia on the
exogenous and endogenous hyperlipidemia models of “Ha mo mau”
granules on the experimental animals.
3. Evaluate the therapeutic effects of “Ha mo mau” granules on

images, 04 diagrams, and appendices.
Chapter 1. OVERVIEW
1.1. Blood Lipid Disorders (dyslipidemia) according to Modern
Medicine
* Definition: Dyslipidemia is an increase in Cholesterol (TC),
Triglyceride (TG) plasma or both, or a decrease in high density
lipoprotein (HDL-C), or an increase in low density lipoprotein (LDLC), causing an increase in the process of atherosclerosis.
* Causes of dyslipidemia
- Primary dyslipidemia
Primary dyslipidemia caused by gene mutation increases excessive
synthesis of TC, TG, LDL-C or decreases TC clearance, TG, LDL-C or
decreases synthesis of HDL-C or decreases HDL-C clearance.
- Secondary dyslipidemia
The cause of secondary dyslipidemia is due to the sedentary
lifestyle, high consumption of beer and alcohol, foods rich in


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saturated fat. Other secondary causes include: diabetes, nephrotic
syndrome, azotemia, hypothyroidism, obstructive liver disease, oral
contraceptives, beta-sympathetic inhibitors etc.
* Blood Lipid Disorders (dyslipidemia) and cardiovascular disease
Dyslipidemia is the main cause of cardiovascular complications. A
pooled analysis of more than 90,000 patients who participated in
randomized trials assessing the effectiveness of statin drugs showed
that for each 10% reduction in LDL, there was a 15.6% reduction in
stroke risk. In Heart Protection Study [HPS]), 20,536 patients with
atherosclerotic arterial disease or diabetes were randomized to
simvastatin (40 mg) or placebo. The treatment helped reduce 18% of
cardiac death, 38% of myocardial infarction rate and 22% of the rate

causing the disordered process of nutrient circulation.
* Clinical form according to traditional medicine
- Internally blocking low sputum: obesity, headache, chest
distiches, nausea or vomiting, un-thirsty dry mouth, heavy limbs,
sebum tongue, whitish moss, active vessels.
- Phlegm-heat fu-organsthenia: heavy body with strong head,
tension, irritation, red face, red eyes, bitter mouth, chest tightness,
irritability, bloating, pink tongue yellow greasy, active vessels.
- Spleen and kidney yang deficiency: face edema, back and knee
pain, fear of cold, tired spirit, belly loose, loose urine, nocturnal
blanching, the edge of tongue has teeth point, white moss, deep vessels.
- Liver and kidney yin deficiency: pain in the back and knees,
irritation, head pain, dizziness, body fatigue, buzzing, sweating, dry
and thirsty mouth, red tongue, little moss tongue, blood vessels.
- Phlegm stagnation and blood stasis: body fat, heavy limbs,
numbness or occasional angina, headache, dizziness, lingering tongue
or bloody spots, thick moss, greasy active or waxed vessels.
- Liver-qi stagnation and spleen deficiency: pain in the ribs,
unstable pain, headache, dizziness and dizziness, poor appetite, tired
spirit, loose defecation, women with menstrual disorders, pale
tongue, greasy tongue moss.
* Study medicine article
Nhi Tran Thang is an ancient medicine written by the author Tran
Su Van in Thai Binh Hue Dan Hoa Te Cuc Phuong in 1151. Rhizoma
Pinelliae plays the role of monarch drug, aiming for dry dampness
and expel phlegm, Pericarpium Citri Reticulatae perenne. is the
minister drug, that aims to regulation “qi”, dry dampness? Poria is an
adjuvant, useful in strengthening spleen and stomach, excreting
dampness. Radix Glycyrrhizae is the guide drug, useful to regulate
medicines, tonify and replenish spleen, strengthening the spleen,

provided by Military Medical University.
2.2.2. Research on humans
- Criteria for selecting patients:
+ According to modern medicine: age 40 or older regardless of gender,
occupation, diagnosis of dyslipidemia is determined: blood test on hunger
has 1 or more of the following lipid indicators: TC> 6 , 2 mmol / l; TG>
2,3 mmol / l; LDL-C> 3,4 mmol / l; HDL-C
kg). Reagents and positive control pills were taken after drinking 2hour cholesterol mixture. Weighing rats in all plots at 1, 2 and 4
weeks before and after the study and taking the tail blood to quantify
blood lipid indexes: TC, TG, HDL-C and LDL-C .
Research on endogenous model: Using and adjusting the model of
endogenous hyperlipidemia by P-407 according to Millar et al. 50
rats were divided into 5 lots: Lot 1 (biological controls), Lot 2
(Controls with disease), Lot 3 (Positive controls, Atorvastatin), Lot 4
(HMM granules dose of 5.4g / kg), Lot 5 (HMM granules dose of
16,2g / kg). Rats were given HMM granules, atorvastatin or distilled
water for 7 days. On day 7, mice in the plots (except Lot 1) were
injected peritoneum P-407. All mice were fasted for 24 hours,
drinking freely. On the 8th day, 24 hours after P-407 injection, all
mice that received carotid artery blood were tested for quantitative
TC, TG, LDL-C, HDL-C.
2.3.3. Evaluate the effect of HMM granules in clinical practice
112 patients were divided into 2 groups: The research group
(HMM group) consisting of 56 patients took HMM granules. Usage:
drink 3 times, 1 pack at a time, after meals 30 minutes, continuously
for 30 days. The control group (lipitor group) including 56 patients
took lipitor 10mg for 1 tablet at 20 hours continuously for 30 days.
Procedures: all patients were examined, medically recorded for
research and testing of blood biochemistry twice before (D0) and
after 30 days of treatment (D30). The patient were given venous
blood in the morning before breakfast and at least 12 hours from the
previous meal. Blood biochemical test (TC, TG, LDL-C, HDL-C).
1. Evaluate results: Evaluate results according to modern
medicine
- Evaluate changes in blood lipid disorders according to NCEP
ATP III and Vietnam Ministry of Health:
+ TC (mmol / l): normal
of decrease by 0.05).
3.1.2.2. Assessment of hematopoietic function

> 0.05

7.23 ± 0.96

6.86 ± 0.47

7.14 ± 0.70

> 0.05

> 0.05

> 0.05

p
(Before - After)
After 8 weeks
p
(Before - After)

p
p1-2 ; p1-3; p2-3
> 0.05
p1-2 ; p1-3; p2-3
> 0.05

p1-2 ; p1-3; p2-3
> 0.05




> 0.05

> 0.05

After 8 weeks

12.31 ± 1.65

11.99 ± 0.74

12.03 ± 1.24

p
(Before - After)

> 0.05

> 0.05

> 0.05

p
p1-2 ; p1-3; p2-3
> 0.05
p1-2 ; p1-3; p2-3
> 0.05

p1-2 ; p1-3; p2-3
> 0.05

> 0.05
(Before - After)

Table 3.7. The effect of Ha Mo Mau granules to platelet count
Platelet count (G/l)
Test lot 1 (2)
Test lot 2 (3)
(n = 10)
(n = 10)

Time

Control lot (1)
(n = 10)

p

Before

360.20 ± 52.55

369.80 ± 74.25 361.70 ± 75.86 p1-2 ; p1-3; p2-3 > 0.05

After 4 weeks

352.50 ± 40.54

359.11 ± 72.33

p

3.1.2.3. The effects of Ha Mo Mau granules to liver function

Chart 3.2. The effect of Ha Mo Mau granules to AST activity

Chart 3.3. Effect of Ha Mo Mau granules on ALT activity
Remarks: After 4 and 8 weeks of taking Ha mo mau granules,
tests assessing liver function (AST activity, ALT; Bilirubin
concentration, Albumin) in rat blood of both test lot 1 and test lot 2
had no significant differences compared to the control group and


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between the two periods before, after 4 and 8 weeks when taking the
reagent (p> 0.05).


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3.1.2.4. Effects of Ha Mo Mau granules to kidney function
Table 3.10. The effect of Ha Mo Mau granules to creatinine content
Time

Creatinine (µmol/L)
Control lot (1)
Test lot 1 (2)
Test lot 2 (3)
(n = 10)
(n = 10)
(n = 10)

Before

81.52 ± 7.80

p
(Before - After)

> 0.05

> 0.05

> 0.05

p
p1-2; p1-3; p2-3
> 0.05
p1-2; p1-3; p2-3
> 0.05
p1-2; p1-3; p2-3
> 0.05

Remark: After 4 and 8 weeks of taking HMM granules, in both
test lot 1 and test lot 2, the concentration of creatinine in rat blood did
not change significantly compared with the control and between two
periods before, after 4 and 8 weeks of taking reagent (p> 0.05).
3.5.2. Effect of Ha Mo Mau granules on experiment
Table 3.14. Blood lipid indicators after 4 weeks of study in
exogenous model (n = 10)
Indicators ( X  SD , mmol/l)
TG
HDL - C
LDL - C

Lot 5: “Ha mo mau”
3.72 ±
0.57 ± 0.09*
1.63 ±
1.83 ± 0.42***
(9.45g/kg)
0.38***
0.13
(↓15.0%)
(↓39.0%)
(% compared to lot 2)
(↓25.1%)
(↓2.4%)
(Note: *: p
(↓26.37%)
(↓22.41%)
Lot 4: “Ha mo mau”
5.45 ±
6.10 ±
2.33 ± 0.31
1.35 ± 0.10**
(5.4g/kg)
0.83**
0.21*
(↓3.09%)
(↓28.95%)
(% compared to lot 2)
(↓18.78%)
(↓19.00%)
Lot 5: “Ha mo mau”
5.42 ±
6.09 ±
2.36 ± 0.13
1.33 ± 0.14**
(16.2g/kg)
0.63***
0.35*
(↓4.42%)
(↓30.00%)
(% compared to lot 2)
(↓19.22%)
(↓19.23%)
(Note: *: p
p0-30
% reduction
16.5
21.1


1.8% of triglycerides at a very high level after treatment for both lots,
there were no patients at this level.
Table 3.3. Changes in LDL-C levels after treatment
Indicator
Lot
Lot HMM (1)
Lot Lipitor (2)
p1-2

D0
3.97 ± 0.79
4.27± 0.83
>0.05

LDL-C
D30
3.16 ± 0.74
3.11 ± 0.61
>0.05

p0-30
% reduction
20.4
26.2

< 0.01
< 0.01

Comment: After 30 days, LDL-C treatment in both lots decreased
significantly with p
17.1
14.4

< 0.01
< 0.01


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Comment: After 30 days, HDL-C treatment in two lots increased
significantly with p 0.05.

Diagram 3.4. The change in HDL-C level after treatment according
to NCEP ATP III and Vietnam Ministry of Health
Comment: At the time of D0, HMM lot had 51.8%, Lipitor lot had
55.3% HDL-C at low level, after 30 days of treatment, HMM lot had
16.1%, Lipitor lot had 19.6% .
Table 3.5. Evaluation on the overall treatment effect of dyslipidemia
according to modern medicine
Lot
Time
Good
Rather
Inefficient
Bad

Lot HMM(1)
n
%

4
0

68.8
27.7
3.5
0

p1-2

>0.05

Comment: The HMM lot achieved a good rate of 36 patients
(64.3%), rather good of 17 patients (30.4%). Ineffective: 3 patients
(5.3%). Lipitor lot achieved good results with 41 patients (73.2%),
rather good: 14 patients (25%). Ineffective with 1 patient (1.8%). The
total rate of good results: 77 patients (68.8%), rather good: 31
patients (27.7%). Ineffective: 4 patients (3.5%). There is no
difference between the two lots (p> 0.05).
 Changes in risk assessment indicators of atherosclerosis.
Table 3.6. Effect of Ha Mo Mau granules on atherosclerosis index (AI)
Indicator
Lots

D0

TC-HDL-C/HDL-C (AI)
D30
% reduction


< 0.01

Comment: After 30 days of treatment, AIP in both lots decreased
significantly with p 0.05.
Table 3.7. Effect of Ha Mo Mau granules on plasma mortar profile (AIP)
TG/HDL-C (AIP)
D30
% reduction
1.70 ± 0.74
34.8
1.83 ± 0.81
27.7
>0.05

p0-30
< 0.01
< 0.01

Remark: After 30 days of treatment, AIP in both lots statistically
significantly reduced with p 0.05.
3.3.2. The effectiveness of HMM granules adopts a number of
clinical criteria
Table 3.3. Clinical symptoms change according to diagnosis
Lots

D0

After treatment: 10 patients (8.9%). The pre-treatment white tongue moss:
100 patients (89.3%), and 15 patients after treatment (13.4%).
Table 3.4. Symptoms change according to diagnosis
Day
Vessels
Active
vessels
Greasy
active
vessels
Other

D0

D30

Lot HMM Lot Lipitor

Total

Lot HMM Lot Lipitor

Total

30 (53.6%) 37 (66.1%) 67 (59.8%) 13 (23.2%) 17 (30.4%) 30 (26.8%)
26 (46.4%) 19 (33.9%) 45 (40.2%) 7 (12.5%) 14 (25.0%) 21 (18.8%)
0

0


Lot HMM

Lot Lipitor

Total

Not
Heavyhea Light
ded
Moderate
Heavy
None
Light
Dizzy
Moderate
Heavy
None
Numbness Light
in
the
Moderate
limbs
Heavy
None
Light
Insomnia
Moderate
Heavy

0

24(42.9%)
1 (1.8%)

0
33 (29.5%)
63 (56.3%)
16 (14.3%)
18 (16.1%)
63 (56.3%)
31 (27.7%)
0
2(1.8%)
42 (37.5%)
60 (53.6%)
8 (7.1%)
24 (21.4%)
36 (32.1%)
42 (37.5%)
10 (8.9%)

36 (64.3%)
20(35.7%)
0
0
38 (67.9%)
18(32.1%)
0
0
46 (82.1%)
10 (17.9%)

2(1.8%)
0
67(59.8%)
41(36.6%)
4(3.6%)
0
60(53.6%)
47(42.0%)
5(4.5%)
0

Comment: At the time of D0, HMM lot had a heavy head rate of
16.1%, medium level was 55.4%. At the time of D30, there was still
0% severe headaches and 1.8% severe headaches.
At the time of D0, the HMM lot had no patients with severe
dizziness, moderate dizziness of 32.1%. At the time of D30, there
were no patients with moderate dizziness.
At the time of D0, the limb HMM lot had severe severity of 5.4%,
moderate level was 44.6%). At the time of D30 there were no serious
and moderate patients.
At the time of D0, the HMM lot had an insomnia of 16.1%, a
moderate level of 32.1%. At the time of D30, there were no serious
insomnia patients, and 3.6% had moderate insomnia.
Table 3.6. Evaluate the effectiveness of treatment according to
traditional medicine


20
Lot
Level


p1-2


Tran, this remedy significantly impacted on LDL and TG. Ngo Dong
Ngoc adopted the study results of the blood fat by Nhi Tran remedy
on rats of insulin antagonist model, the results showed that the Nhi
Tran remedy is effective in reducing TG, especially in reducing TG
and cholesterol
Rhizoma Pinlliae ternatae has phytosterols; Rhizoma Alocaciae
odorae has campestrol; Radix Achyranthis bidentatae has ecdysterol
and inokosterol; Poria Cocos has ergosterol which are plant sterols.
Several clinical trials have shown that the use of plant sterols (2-3 g /
day) reduces LDL-C by 6-15%. Hesperidin in Pericarpium Citri
Reticulatae perenne has effect of reducing the value of TC, TG,
serum density of lipoprotein, particularly in reducing blood fat. In
one study, the conclusion was made for ethanol extract of Radix
Glycyrrhizae at doses of 0.2, 0.7 and 1mg / ml reducing TC, TG,
LDL-C concentrations and increasing HDL-C concentrations in
experimental mice. The goal of treating dyslipidemia is to reduce the
risk of atherosclerosis. To initially assess the risk of atherosclerosis,
we only used atherosclerosis indicator AI (AI = TC-HDL-C / HDL-


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C). In recent years, researchers have been focusing on a new
comprehensive lipid indicator, plasma atherosclerosis indicator (AIP
= TG / HDL-C), which may reflect a comprehensive balance between
the factors causing atherosclerotic and preventing atherosclerosis.
The study results showed that both of these indicators had a
statistically significant decrease compared to that pre-treatment, and
at the same time no difference was recorded compared to the Lipitor
taking lot with p> 0.05. Lipitor is one of statin drugs that have been
proven to prevent atherosclerosis. Thus, it is initially possible to

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with dizziness when changing positions. According to Pham Khue,
this symptom has been seen in 87% of cases of cerebral circulation
insufficiency, mainly caused by atherosclerosis. According to the
traditional medicine, dizziness is under the "illusory" scope while
Don Khe Tam's book says about illussory-causing mechanism: "no
failure causes no dizziness". The symptoms frequently seen in people
who eat a lot of sweet, fats causing damage to the spleen, dysfunction
of circulation, nutrients do not turn into essence but sputum
stagnation in the body, causing dizziness. After treatment, 38 patients
(67.9%) had dizziness ended, 18 patients (32.1%) were still dizzy and
no longer had frequent dizziness.
Insomnia is a major symptom of sleep disorders, which is both a
symptom of cerebral atherosclerosis and a pathophysiological factor
that aggravates the progression of the disease. Early-stage of cerebral
atherosclerosis is usually insomnia in the first half of the night, and at
the later stage, insomnia occurs in the latter half of the night.
According to traditional medicine, insomnia suffers from a lack of
sleep. The cause may be due to much anxiety, fatigue that makes
mind feel weak, blood loss and no-sleeping. The book record
"Negligence of spleen, spleen and blood loss, many years without
sleep". Or due to uncontrolled eating, eating spicy, hot, sweet fat,
drinking a lot of alcohol hurts the spleen, food stagnates at the center,
causing thermal sputum rise up, leading to un-peaceful spirit and
unable sleeping. As the ancient book of medicine said "The spleen
discords, un-peaceful sleeping". In the HMM lot, the proportion of
insomnia patients was 43 (76.8%) of which 9 patients (16.1%)
suffered from severe insomnia. After 30 days of treatment, 29
patients (51.8%) ran out of insomnia completely and there were no
serious insomnia patients.

stagnation elimination. Besides the lipid-lowering effect of the
medicinal herbs in the remedy, it has been proved by
pharmacological studies of modern medicine, the combination of
roles of Main ingredient, Assistant ingredient, Adjuvant ingredient
and Guidant ingredient in the remedy brings effect of spleen
strengthening and sputum eliminating, rheumatics tonifying, from
that improving significantly the clinical symptoms.
4.3.3. No unwanted clinical effects
CONCLUSIONS
1. The experimental results of acute toxicity and semi-chronic
toxicity of Ha Mo Mau granules
When rats were administered HMM granules at doses of 9g / kg to
45g / kg (8 times higher than the equivalent dose in humans) which is
the maximum dose that can be given to rats but no mice died during
the 7-day follow-up. Therefore, it is not possible to identify toxic
levels and calculate LD50 in white mice by oral route.
HMM granules do not show semi-chronic toxicity in white rats
when rats were administered at a dose of 3.15g / kg (equivalent to
human dose) and 9.45g / kg (3 times higher the human dose) in 8
continuous weeks; No adverse effect was recorded in the general
condition, and no affect was recorded in function of liver, kidneys, rat
liver and histopathology.


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2. The resulted effect of blood lipid disorders adjustment using
Ha Mo Mau granules in experimental animal models
* In the model of exogenous hyperlipidemia, HMM granules at
dose of 3.15g and 9.45g / kg for 4 weeks both reduced TC, TG, and
LDL-C, equivalent to Atorvastatin.