Nghiên cứu độc tính, tác dụng của “hoàn chỉ thống” trong điều trị bệnh lý viêm khớp dạng thấp trên thực nghiệm và lâm sàng tt tiếng anh

INTRODUCTION
Rheumatoid arthritis is a bone and joint disease found everywhere in the
world, accounting for about 1% of the population. In Vietnam, the rate of
rheumatoid arthritis accounts for 0.5% of the population and 20% of
arthritis diseases. Rheumatoid arthritis is prolonged, alternates with acute
attacks, causes disability, and greatly affects work performance and daily
life.
The treatment of rheumatoid arthritis requires a combination of different
methods: internal medicine, physical therapies, rehabilitation, and
surgery. Researching to find an effective and less-side-effects
medicination for the treatment of rheumatoid arthritis has been being a
target for researchers.
There is no name for rheumatoid arthritis disease in traditional medicine.
The symptoms of rheumatoid arthritis in traditional medicine belong to
the category of pain due to stasis, such as, acute arthritis, crane knee
arthritise, etc. Traditional medical literature has mentioned the causes,
mechanisms of pathogenesis, treatment methods for rheumatoid arthritis.
‘Hoan chi thong’ remedy is a herbal product made of Tinospora sinensis,
Gnetum montanum Mgf, Angelica dahurica, Achyranthes bidentata,
Cinnamomum, and Sargentodoxa cuneata. According to the traditional
medicine theory ‘Hoan chi thong’ remedy has the effects dispelling wind
evil, removing dampness, activating blood, activating and smoothing
meridians, tonifying blood qi, nourishing liver and kidney, antiinflammatory, analgesic, the medicine is indicated to treat the
osteoarthritis including rheumatoid arthritis. However, there are no
scientific studies evaluating the treatment effects of rheumatoid arthritis
of the drug ‘Hoan chi thong’. Therefore, we carry out this research with
the following objectives:
1. Assessing the acute and semi-chronic toxicity of ‘Hoan chi thong’
in experiment.
2.Evaluating the analgesic and anti-inflammatory effects of ‘Hoan
chi thong’ in experiment.

3. Evaluating the therapeutic effects and undesirable effects of
‘Hoan chi thong’ on patients with rheumatoid arthritis stage 1 and 2.
PRACTICAL MEANINGS AND NEW CONTRIBUTION OF THE
THESIS

The rapid development of economy, society, and disease patterns in
Vietnam has changed markedly in recent years, from infectious diseases
1


to non-communicable diseases. Rheumatoid arthritis is a cause of
complicated consequences for joints and disability, which affects work
efficiency and daily life. Modern medicine has shown a positive role and
effectiveness in the treatment of rheumatoid arthritis, but it also causes
some side effects of peptic ulcer, gastrointestinal bleeding, osteoporosis,
etc. Therefore, searching for effective and safe herbal medicines is
always a need and is of interest to national and international scientists.
The scientific work of the thesis is experimentally and clinically
organitinal and systematical.
The research and application of the medicine contribute to the
clarification of traditional medicine theory and gradually modernize
traditional medicine and is a scientific and practical work.
STRUCTURE OF THE THESIS
The thesis consists of 123 pages, of which: Introduction: 02 pages;
Overview: 37 pages; Research subjects and methods: 18 pages; Research
results: 28 pages; Discussion: 35 pages; Conclusion: 02 pages
Recommendations: 01 page.
The thesis has 120 references (48 in Vietnamese, 37 in English, and 35 in
Chinese), 43 tables, 12 charts, 04 diagrams, 02 pictures, 12 photos and
appendices.

Chapter 1. OVERVIEW
1.1. Rheumatoid arthritis from the modern medical perspective
Rheumatoid Arthritis:Rheumatoid Arthritis is an autoimmune pathology
characterized by chronic inflammatory processes of joints, if it is not
treated thoroughly or properly, joint disfigurement, deformation, and loss
of motor movement would be consequences.
Rheumatoid arthritis develops complicatedly over many stages, in
addition to presenting at joints, it might exist in the whole body at
different degrees. Rheumatoid arthritis can also cause damage to organs
such as heart (pericarditis, endocarditis, myocarditis, arrhythmia, etc.),
respiratory system (pleural effusion, fibrosis, etc), nerves (carpal tunnel
syndrome), etc.
Cause: The cause of the disease is not clear, modern medicine has
recently considered rheumatoid arthritis as an autoimmune disease with
the participation of many factors. A number of common viruses or
bacteria affect the favorable atopic and genetic factors. Rheumatoid
arthritis has a family nature.
2


Pathogenesis: rheumatoid arthritis is an autoimmune disease,
characterized by chronic inflammatory reactions that damage synovial
membranes, cartilage and bone at inflamed joints. Although the etiology
of the disease is still unclear, new knowledge on immunology and
molecular biology has contributed to further elucidation of the
mechanism of rheumatoid arthritis.
Diagnosis standards: rheumatoid arthritis is diagnosed by a variety of
criteria over time, such as the American college of Rheumatology: ACR,
1958, and the Roman standard (1961). By 1987, the American
Association of Rheumatology had agreed to improve the diagnostic

criteria for ACR (1987), including 7 factors that are still widely applied
in the world.
1.2. Rheumatoid arthritis according to traditional medicine
* Reasons
Traditional medicine believes that the main causes of the disease is due
to qi deficiency and evil qi. Yang qi deficiency, weakend protective qi,
and opening pores lead to wind, cold, wetness evils invading muscles,
meridians, and joints), which causes diseases.
* Pathogenesis mechanism
- Onset of the disease: due to external evils, either wind cold wetness
evils or wind wetness heat evils, initially, the disease is acute. The basic
manifestations are muscle aches and pains, numbness in the limbs,
limited joint activities and the whole body feeling heavy, etc.
- Positions: mainly in muscles, meridians, and joints. Since liver
determines tendon, spleens determine muscles, and kidney determines
bones, the diease is closely related to these organs. Prolonged disease
will affect heart and kidneys, or even all the five organs.
- The nature of the disease: the onset or progression of the diease is
mainly caused by wind, cold, wetness, heat or blood stastic, dyslipidemia
,mostly of plenitude sthenia syndrome. In the late stage, there is often the
presence of yin qi deficiency, or damages of kidney and liver
accompanied by phlegm stagnation, which causes asthenia accompanied
with plenitude, of which the manifestation is plenitude sthenia
syndrome .
* Types of diseases according to traditional medicine
- Wind wetness type: aches and pains in musles and joints, dull pains,
unpleasant feeling of heaviness, painful points are not fixed; May be
accompanied by swelling; Limited joint muscle movements; The onset
of the disease is most frequently accompanied by diseases of superficies
3

such as fear of wind, fever, pale tongue; Whitish tongue moss; Floating
moderate pulse or solf moderate pulse.
- Cold wetness type: limbs, body, muscles, and joints feel cold and
painful; Feelings of heavy, irritated, and uncomfortable; The disease is
more severe at night than day, the pain increases when it’s cold, and hot
compresses may help with pain; At swollen joints , there are stiff and
limited joint movements; non reddish color and non burning skin.
Whitish tongue moss; Tense taut pulse or tense moderate pulse.
- Wetness heat type: joints are swollen, burning, reddish, and painful;
Feeling heavy, accompanied by fever, thirst but do not want to drink
water; Feeling irritated and uncomfortable, yellowish urine, limited joint
movements; There are benign tumors under the skin; Redish tongue,
yellowish tongue moss; Rapid soft pulse or rapid taut pulse.
- Phlegm stasis type: patients with prolonged illness feel severe pain like
needle pricking, joints become swollen, bruised, and deformed; Joint
movements are limited; There are benign tumors under the skin;Tongue
is purplish with rashes, white viscous moss; Rapid fine taunt deep pulse.
- Blood stasis type: Muscle aches and pains like needle pricking; Pain
points are often fixed; Irritated pain persists; swelling, rashes or benign
tumors under the skin; Dark face and dry skin; Dry mouth but unlike to
drink; Purplish tongue with blood stasis spots, thin whitish and yellowish
moss; Sluggish fine taut deep pulse.
- Blood qi deficiency type: swollen joints, aches, muscle atrophy,
stiffness, deformed joints, limited joint movements; The disease is
accompanied with dizziness, poor appetite, dry skin, or bleeing; There
are benign tumors under the skin; The tongue is pale or redish or with
cracks, thin whitish moss with little or no moss; Fine deep pulse or weak
fine pulse.

- Liver-kidney deficiencyn type: swollen joints, aches, stiffness, muscle
atrophy, deformed joints, limited joint movements; Accompanied with
back and knee pain, afraid of cold, cold limbs, sleeplessness; Bone heat
sydrome and hectic fever; Dry mouth but drink little or dislike to drink
water. Reddish or pale tongue, thin tongue moss, Weak taut deep pulse or
rapid taut pulse.
* Research remedies
‘Hoan chi thong' is produced by the Military Traditional Medicine
Institute under a science and technology project of the Ministry of
Defense. It includes Tinospora sinensis, Gnetum montanum, Angelica
dahurica, Achyranthes bidentata, Cinnamomum, and Sargentodoxa
cuneata. They are common ingredients used in the treatment of
4


osteoarthritis diseases such as: osteoarthritis, rheumatoid arthritis, gout,
etc. The remedy has the effects dispelling wind evil, removing dampness,
activating blood, activating and smoothing meridians, tonifying blood qi,
and nourishing liver and kidney, anti-inflammatory, analgesic, and it is
indicated to treat the osteoarthritis including rheumatoid arthritis.
Chapter 2. SUBJECTS AND METHODS OF THE STUDY
2.1. Research material
Research medication: 'Hoan chi thong' is produced by the Faculty of
Pharmacy, the Military Traditional Medicine Institute, is formulated to
soft medicated balls, and weighs 8.5g/ ball. The medication meets the
standardsof the institute.
Research materials: Aspirin, prednisolone, carrageenin solution,
formaldehyde, amiant fiber, etc.
2.2. Research subjects
2.2.1. Research on animals

- Swiss white mice, both sexes, healthy, weigh 25 ± 2g, provided by the
National Institute of Hygiene and Epidemiology.
- White rats of the Wistar strain, both sexes, healthy, weigh 150 - 180g,
provided by the Military Medical Academy.
2.2.2. Clinical research
- Rriteria to selecting patients: the patients diagnosed with rheumatoid
arthritis according to the standards of the American Association of
Rheumatology and the European Anti-Rheumatology Federation 2010
ACR / EULAR 2010. If the patient has at least 4/7 criteria and clinical
symptoms that persist for more than 6 weeks, they are diagnosed with
rheumatoid arthritis. Selected patients who meet the criteria for diagnosis
according to modern medicine as above and in accordance with the
evidence diagnosis of traditional medicine. The patients were examined
according to 4 methods of examination: inspection, listening and
smelling, questioning, and palpation. the symptoms were devided into
two main categories: wind cold wetness type and wind wetness heat
type.
- Criteria to excluding patients: Patients with liver, kidney, and
infectious diseases, diseases of the hematopoietic system, diabetes and
those who suffer from mental neurological diseases, sensory disorders,
cancer, etc.
2.2.3. Location, study time
5


The experimental and clinical research was conducted at the Military
Traditional Medicine Institute, from February 2015 to November 2017.
2.3. Research Methods
2.3.1. Acute and semi-chronic toxicity study
Acute toxicity: The acute toxicity is determined in accordance with the

guidelines of the Ministry of Health and OECD on the white mice by
oral route, with 6 groups of 10 heads each, receiving reagents in
increasing doses from 12.2g/kg to 61g/kg (maximum tolerable dose for
mice) the general condition of the rats and the number of dead mice in
each group were monitored in 72 hours (mice that died within the first 24
hours were operated for the macro image observation) ). The calculation
of LD50 was done by Litchfield-Wilcoxon method.
The study on the chronic toxicity was under the regulations of the
Ministry of Health of Vietnam and the guidance of OECD and WHO.
'Hoan chi thong' was taken orally by white rats. 30 experimental mice
were divided into 3 groups of 10 heads each; the control group drank
distilled water at a dose of 2 ml/kg/day; the research group 1 took 'Hoan
chi thong' 4.8g/kg (equivalent to the human dose), the research group 2
took the 'Ha mo mau' nuggets 14.4g/kg/day (equivalent to 3 times the
human dose).
Monitoring criteria: The general condition and body weight of white
rats. The evaluation of hematopoietic function, assessment of liver and
kidney function, liver histopathology, kidney rats' kidney.
Evaluation time: before the treatmemt, after 2 weeks, and 4 weeks of the
treatment.
2.3.2. Experimental research on the analgesic and anti-inflammatory
effects
- Studying the etopic analgesic effect by Koster method
- Studying the central analgesic effect using hot plate
- Studying the acute anti-inflammatory effects on edema-induced by
carrageenin model.
- Studying the acute anti-inflammatory effect on the peritonitis-induced
model
- Studying the acute anti-inflammatory effect on the vascularpermeability-inhibition model: Assessing the acute anti-inflammatory
effect on Anderson K.W.-vascular-permeability-suppression model.

- Studying the chronic anti-inflammatory effects on Ducrot R., Julon L.
et al granulomatous model (1965).
2.3.3. Studying the effect of ‘Hoan chi thong’ clinically
6


Research design: clinical trial, cross-sectional description with
intervention, vertical monitoring. Compare results before and after the
treatment.
The treatment: 60 patients with rheumatoid arthritis took 4 balls of 'Hoan
chi thong' daily, 2 in the morning and 2 in the afternoon; 1 hour after
eating, the duration of treatment is 30 consecutive days.
Patients with chronic cardiovascular disease, blood pressure are allowed
to use specialized drugs prescribed by a doctor. Patients with severe pain
who are recommended to use painkillers should receive Celebrex 200mg.
Clinical and subclinical research criteria
* Diagnosis of rheumatoid arthritis: under the EULAR/ACR 2010
standards.
* Monitoringthe criteria according to traditional medicine: Classifying
the patients according to the clinical form of wind cold wetness type and
wind wetness heat type. After the clinical classification, comparing the
responses of patients in these two groups to the assessment criteria of
rheumatoid arthritis in modern medicine.
* Subclinical monitoring criteria:
- Hand pressure is measured by a Japanese hand dynamometer. When
being measured, the patient's arms were spreaded horizontally, three
times each hand and the highest results were taken. The unit of
calculation is kg. Blood test: red blood cell count, white blood cell count,
white blood cell count, platelet count, hemoglobin, sedimentation rate.
Biochemistry: glusose, total protein, AST, ALT, GGT, total bilirubin,

urea, creatinine, uric acid.
- Testing for rheumatoid factor (RF), quantification of CRP.
- 10-parameter urine tests by automated machine; Heart X-ray, joint Xray, abdominal ultrasound, ECG.
* Assessing unwanted effects: Monitoring clinical undesired effects such
as headache, dizziness, nausea, loose stools, rashes, abdominal pain,
joint pain increase ...
* Data processing: The data collected in the study was processed by the
biomedical statistical method using SPSS 22.0 software.
* Ethics in the research: the research is conducted under the Scientific
and Ethical Council of the Military Institute of Traditional Medicine, the
patients understood and voluntarily participated in the research, all the
patients’ personal information kept confidentially, only aggregated
results are published.
Chapter 3. RESULTS
7


3.1. Acute and semi-chronic toxicity study results
The 50% lethal dose (LD50) of ‘Hoan chi thong’ at a dose of 61g/kg
was not determined (the highest dose likely to be given to rats under
laboratory conditions).
* The results of the semi-chronic toxicity evaluation
- The effects of ‘Hoan chi thong’ on the general conditions and weight
change of white rats after taking the medicine: during the experiment,
the experimental mice in all 3 groups were normal and agile, had silky
hair, good appetie, and firm feces.
After 2 weeks and 4 weeks of reagents, the weight of mice in all 3
groups (01 control and 2 research groups) was higher than that of the
before-test (p <0.05). There was no difference in the degree of the
increase in the mice weight between control group and research groups

at the same time of testing (p> 0.05).
- Effects on the hematological indicators: There were no differences in
the number of erythrocytes, hemoglobin content, white blood cells, and
platelets, hematocrit concentration, and the percentage of neutrophils and
lymphocytes between the control group and the research groups and
between 2 research groups at the same testing times (p> 0.05).
- Effects on the liver function: There are no differences in the acctivity of
AST, ALT, total bilirubin enzymes in white rats blood between the
control group and the research groups and between 2 research groups at
the same testing times (p> 0.05).
- Effects on the kidney function:There are no differences in the urea
concentration and serum creatinine concentration of rats between the
control group and the research groups and between 2 research groups at
the same testing times (p> 0.05).
* The changes in the histopathology
- Macro image: There are no differences in the macroscopic morphology
of kidney between the control group and the research groups and
between 2 reaserach groups at the same testing times. Smooth kidney
surface, evenly shinny, reddish-brown color can be seen and there were
no bleeding and elastic when being pressed.
- Liver microscopic morphology (HEx400):

8


Control group
Research group 1
Research group 2
The HEx400 image showed that Remak was formed in central vein of
the liver cells. The image of broken or dissolved liver cells were not

seen. The images of hemorrhage or necrosis in the lobes of the uterus
were not seen. Conclusion: Normal liver images. The liver microscopic
morphology images in the 2 study groups were not different from the
control group.
- The microscopic morphology images of kidney (HEx400):

Control group
Research group 1
Research group 2
The HEx400 kidney microscopic morphology images of the control
group showed glomerular, Bowman cavity, capillary coil, and tubule.
The nucleus of the glomerular cells and tubular became dark. Glomerular
and tubular lesions were not seen. Conclusion: Normal kidney images.
The Micrograph of kidney in the 2 study groups were not different from
that of the control group.
3.2. Results of the pharmacological effects evaluation
3.2.1. Results of empirical analgesic effect evaluation
* Peripheral analgesic effect by the acetic acid pain induced method
5 minutes after the injection, the pain of mice in the Aspirin group dose
100mg/kg and ‘Hoan chi thong' dose 6.8g/kg group decreased
significantly compared to the other two groups (p <0 , 05). After 10, 15
and 20 minutes, the number of pain in the white mice that took‘Hoan chi
thong' dose 6.8g/kg/day decreased significantly compared to control
group and taking‘Hoan chi thong' dose 13.6g/kg (p<0.05). After 25 and
30 minutes, the number of pain in the white mice taking‘Hoan chi thong'
dose 6.8g/kg/day decreased significantly compared to the other groups (p
<0.05).
* Central analgesic effect of ‘Hoan chi thong' by hot plate method
Table 3.1. Effects of ‘Hoan chi thong' on reaction time to temperature of
white mice (seconds;  SD)

Groups
Group 1 (control)
Group 2 (Codein 10 mg/kg)

Reaction time
Before (a)
After (b)
12.23 ± 1.51
11.91 ± 1.71*
12.05 ± 1.84
20.29 ± 2.42

9

pa-b
>0.05
<0.05


Group 3 (HCT 6.8g/kg/day)
Group 4 (HCT 13.6g/kg/day)

11.30 ± 1.33
11.91 ± 1.53

11.82 ± 1.60*
12.16 ± 1.71*

>0.05
>0.05

T he a bility to inhibit fo o t e de m a (% )

Comments: the reaction time to temperature of rats in both doses of
‘Hoan chi thong' after taking the medicination was not different from
that of the control group (p> 0.05). After taking the medicination, the
reaction time of mice in the codeine phosphate group was significantly
longer than the ‘Hoan chi thong' and the distilled water group (p <0.05).
3.2.2. Results of anti-inflammatory effect on trials
* The acute anti-inflammatory effect on the foot-edema-caused-by
carrageenin model
50 39.37
40
30
20
10
0
-10 V2
-20
-30
-40

33.79

25.81
13.23
14.5
-5.72

V4

Aspirin

V6

Time

17.62

V24

-8.49

HCT 4.8g/kg

Figure 3.1. The ability to inhibit foot edema compared to the control
group
Comments: the ability to inhibit the food edema reaction compared to
the control group 2 hours after the injection in the aspirin group was
better than the 2 ‘Hoan chi thong’ groups. 4 hours, 6 hours, and 24 hours
after the injection, the ability of mice to inhibit the foot edema of the
Aspirin group ‘Hoan chi thong’ 4.8g/kg body weight was equivalent (p>
0.05). ).
* Acute anti-inflammatory effect on the peritonitis caused by
carrageenin + formaldehyde solution model
Table 3.2. The effect of ‘Hoan chi thong’ on the inflammatory exudate
test criteria
Groups

Inflammatory Proteincontent

exudate (ml)
(mg/dl)

Group 1: distilled water
4.90  0.70
ml/100g
Group 2: aspirin 150
2.05  0.69*
mg/kg
Group 3: HCT 4.8 g/kg
2.06  0.51*
Group 4: HCT 9.6 g/kg 3.69  0.42*▲■

10

White blood
cells (K/ul)

5.53  0.51

13.82  3.36

2.90  0.42*

6.76  0.76*

3.16  0.37*
5.04  0.35*▲■

7.01  0.98*

10.89  2.80▲■


Comments:The ‘Hoan chi thong’ dose of 4.8 g/kg body weight reduced
inflammatory exudate, reduced protein content in the exudate and
reduced the number of white blood cells in inflammatory exudate
compared to the control group (p <0.05), equivalent to the aspirin dose
150mg/kg body weight (p> 0.05).
* The anti-acute inflammatory effect on the vascular permeability
inhibited model
Table 3.3. Effect of ‘Hoan chi thong’ on the concentration of abdominal
fluid
Group

Pigment concentration

Group 1: distilled water0.2ml/10g body weight
Group 2: Aspirin 200mg/kg body weight
Group 3: ‘Hoan chi thong’ 6.8 g/kg

0.272  0,.
0.125  0.088*
0.180  0.048*▲

Comments: ‘Hoan chi thong’dose of 6.8g / kg body weight had the effect
of inhibiting the amount of pigment released from the lumen of the blood
significantly better than that of the control group, the difference was
statistically significant with p <0.05. The effect of inhibiting the amount
of pigments exiting the lumen of the ‘Hoan chi thong’ was lower than that
of mice taking aspirin in the same test conditions with p <0.05.

* The anti-chronic inflammatory effect of the ‘Hoan chi thong’ in the
granulomas caused model
Table 3.4. The effect of ‘Hoan chi thong’ on granulomatous weight
Groups
Group 1: distilled water0.2ml/10g (1)
Group 2: Prednisolon 5 mg/kg (2)
Group 3: ‘Hoan chi thong’ 6.8 g/kg (3)
Group 4: ‘Hoan chi thong’ 13.6 g/kg (4)

Granulomatous weight
(mg)
30.96  5.88
19.70  4.70*
18.21  3.98*
25.95  4.73▲■

Comments: After 7 days of continuous use of the medicination, the
granulomatous weight in the ‘Hoan chi thong’6.8g/kg body weight
significantly decreased compared to that of the control group (p <0.05)
and equivalent to the reduction of the prednisolone group (p> 0.05).
3.3. Clinical research results
3.3.1. Patient characteristics
Table 3.5. Age and gender of the patients
Gender
Total
Age
Male
Female
group Number of Percenta Number of Percentage Number of Percentage
patients

ge (%)
patients
(%)
patients
(%)

11


<60

7

11.7

24

40.0

31

51.7

≥60

4

6.7

25

41.7

29

48.3

Total

11

18.3

49

81.7

100.0

Mean

55.91 ± 13.16

60
58.60 ±
11.95
(33-79)

59.20 ± 11.72
p>0.05

Comments: The average age of rheumatoid arthritis patients is 58.60 ±
11.95 years old. The proportion of female patients (81.7%) was higher
than the male patients (18.3%). The mean age of the male group was not
different from the female group (p> 0.05).
Table 3.6. Occupation and duration of disease
Indexes
Disease duration
Accupation

Number of Percentage %
patients
20
33.3
40
66.7
6.57 ± 4.47
20
33.3
40
66.7

1- 10 years
11- 25 years
± SD (years)
Intellectual labor
Unskilled labor

Comments: The average duration of the disease was 7.95 ± 6.09 (years),
the majority of patients had the duration of disease from 11-25 years

(66.7%). The target group was unskilled workers with high proportion
(66.7%).
Table 3.7. Characteristics of the disease according to traditional
medicine
Traditional medicine disease
type

Number of patients

Percentage %

44
16
60

73.3
26.7
100.0

Wind wetness heat type
Wind cold wetness type
Total

Comments: most patients with rheumatoid arthritis belong to the wind
wetness heat type (73.3%); 26.7% of the patients belongs to wind cold
wetness type.
3.3.2. Research results on the analgesic effect of 'Hoan chi thong' on
clinic
Table 3.8. Time of stiffness before and after the treatment
Indexes

Time of joint stiffness (minute)
Changes the time of joint stiffness

Time
D0
D28
46.83 ± 20.66
17.17 ± 8.04
30.00 ± 15.12 (5-70)

12

p
<0.001


Comments: After the treatment, the joint stiffness time in the morning
decreased significantly (p <0.001), the average was 30.00 ± 15.12
minutes. 100% of patients reduced the joint stiffness time in the
morning, of which 8.3% of the patients decreased by 20-49%; 71.7% of
the patients reduced by 50-69%, and 20.0% of the patients improved by
≥70%.
Table 3.9. Number of sore joints before and after the treatment
Time
D0
D28
16.02 ± 5.51
3.03 ± 2.00

Indexes

Number of sore joints
Changes in the number of painful
joints

p
<0.001

12.98 ± 4.48 (2- 20)

Comments: After the treatment, the number of sore joints decreased
significantly (p <0.001), the average was 12.98 ± 4.48 joints. In
particular, 100% of patients decreased ≥20% of the number of sore
joints, of which 6.7% of the patients decreased by 50-69%, and 93.3% of
the patients decreased by ≥70%.
Table 3.10. Ritchie index before and after the treatment (n = 60; ± SD)
Time

Indexes
Ritchie index (score)
Changes in Ritchie indexes

D0

D28

24.78  8.28

3.05  2.04

P

<0.001

21.73  7.15 (4-34)

Comments: After the treatment, the patient's Ritchie index decreased
significantly (p <0.001), the average was 21.73 7.15 points. In
particular, 100% of patients decreased by≥ 20% of the Ritchie index, of
which 98.3% of patients decreasedby ≥ 70% and 1.7% of patients
decreased by 50 - 69%.
Table 3.11. The pain score before and after the treatment according to
VAS1 scale
Time (n= 60;± SD)

Indexes
Pain score (VAS1)
Changes in pain
(VAS1)

D0
7.02 ± 0.72
score

D28
1.72 ± 0.95

P
<0.001

5.30 ± 0.59

Comments: After the treatment, the pain score decreased significantly (p
<0.001), the average was 5.30  0.59 points. 100% of the patients
13


decreased by ≥20%, of which 23.3% of patients decreased by 50-69%,
and 76.7% of the patients reduced by ≥70%.
- Changes in the number of non-steroidal anti-inflammatory analgesic
used in the treatment
During the treatment, 05 patients had to take Celebrex 200mg, 1-2 times
a day, 1 tablet/time after eating in 3-5 days, the total dose of Celebrex
was 30 tablets (6000mg).
-The severity of disease assessed by the patients (VAS2) before and after
the treatment
Table 3.12. The severity of disease assessed by the patients on the VAS2
scale
Indexes
Activity score (VAS2)

Time (n= 60;± SD)
D0
D28
6.65 ± 0.65
2.03 ± 0.75

Changes in activity score (VAS2)

P
<0.001

4.61 ± 0.80

Comments: After the treatment, the level of disease activity assessed by
the patients decreased significantly (p <0.001), the average was 4.61 ±
0.80 points. In particular, 100% of the patients decreased by≥20%, of
which 1.7% of the patients decreased by 20-49%, 36.7% of the patients
decreased by 50-69%, and 61.7% of the patients decreased by ≥70%.
Table 3.13. The degree of disease assessed a physician with VAS3
Indexes
Activity score (VAS3)
Changes in activity score (VAS3)

Time (n= 60;± SD)
D0
D28
6.53 ± 0.62
2.13 ± 0.79

P
<0.001

4.40 ± 0.80

Comments: After the treatment, the score of disease activity assessed by
physicians decreased significantly (p <0.001), the average was 4.40 ±
0.80 points. 100% of patients decreased by ≥20% of disease activity on a
VAS3 scale, of which 5.0% of patients decreased by 20- 49%, 43.3% of
patients decreased by 50-69%, and 51.7% of patients decreased by
≥70%.
3.3.3. Research on anti-inflammatory effect of 'Hoan chi thong’ in

clinic
Table 3.14. Number of swollen joints before and after treatment
Indexes
Number of swollen joints

Time (n= 60;± SD)
D0
D28
7.53 ± 4.21
1.17 ± 1.26

14

P
<0.001


Changes in the number of
swollen joints

6.36 ± 3.31

Comments: After the treatment, the number of joints decreased
significantly (p <0.001), the average was 6.36 ± 3.31 joints. In particular,
100% of patients reducedby ≥20% of the number of swollen joints, of
which 6.7% of the patients decreased by 50-69%, and 93.3% of the
patients decreased by ≥70%.
Table 3.15. The sedimentation rate of blood before and after the
treatment
Time (n= 60;± SD)

D0
D28
47.85 ± 24.90 30.28 ± 13.07

Indexes
Sedimentation rate of blood (mm)
Changes in the sedimentation rate
of blood

P
<0.001

17.56 ± 14.24

Comments: After the treatment, the sedimentation rate of blood
significantly decreased (p <0.001), the average was 17.56 ± 14.24 mm.
78.3% of the patients decreased by ≥20%, of which 63.3% decreased by
20- 49%, and 15.0% of the patients decreased by 50- 69%).
Table 3.16. C-reactive protein before and after the treatment
Time (n= 60;± SD)

Indexes
C-reactive protein (mg/l)
Changes
protein

in

the

C-reactive

D0
14.35 ± 10.19

D28
9.56 ± 2.47

P
<0.001

4.79 ± 10.00

Comments: After the treatment, the CRP concentration decreased
significantly (p <0.001), the average was 4.79 ± 10.00 mg/l. In particular,
73.4% of patients decreased by ≥20% CRP, of which 71.7% decreased
by 20-49% and 1.7% of patients decreased by ≥70%.
3.3.4. Effect of improving disease activity level of ‘Hoan chi thong’
Table 3.17. Mobility function according to HAQ before and after the
treatment
Indexes
Mobility function HAQ (points)
Changes in the mobility function

Time (n= 60;± SD)
D0
D28
2.92 ± 0.74

1.57 ± 0.62

p
<0.001

1.35 ± 0.48

Comments: After the treatment, the decrease in motor function points
was statistically significant (p <0.001), the average was 1.35 ± 0.48
points. In particular, 100% of patients decreased by ≥20%, of which,
15


33.3% of the patients decreased by 20-49% and 66.7% of the patients
decreased by 50-69%.
Table 3.18. Hand grip strength before and after the treatment
Indexes

Time (n= 60;± SD)
p
D0
D28
80.05  18.78 87.37  15.24 <0.001

Dominant hand grip strength (kg)
Changes in the dominant hand grip
7.32  7.07
strength (kg)
Non-dominant hand grip strength
<0.001
71.08  18.64 76.65  14.89

(kg)
Changes in the non-dominant hand
5.56  6.90
grip strength (kg)

Comments: After the treatment, the dominant and non-dominant hand
grip strength did not significantly increase (p <0.001), the averages were
7.32 ± 7.07 and 5.56 ± 6.90 (kg).
Table 3.19. Percentage of patients improving ACR by 20%, 50% and
70%
Indexes

Number of
patients
0
60
59
13

No improvement
ACR20 Improvement
ACR50 Improvement
ACR70 Improvement

Percentage (%)
0
100.0
98.3
21.7

Comments: After the treatment, the percentages for the improvements
ACR 20, ACR 50, and ACR 70, were 100.0%, 98.3%, and 21.7%,
respectively.
Table 3.20. The decrease in disease activity according to DAS28 using
CRP
Criteria
DAS28 - CRP

Time (n= 60;± SD)
D0
D28
5.79 ± 0.73
3.08 ± 0.68

Improvement of the DAS28CRP

p
<0.001

2.70 ± 0.53

Comments: After the treatment, the DAS28-CRP index decreased
significantly (p <0.001), the average reduction was 2.70 ± 0.53. In
particular, 100% of patients improved their disease activity according to
DAS28-CRP, of which 1.7% of the patients improved moderately and
98.3% of patients improved well.
3.3.5. The degree of disease improvement according to traditional
medicine disease
16

Table 3.21. Therapeutic effects of traditional medicine disease types
according to Ritchie index

Changes

50- 69%
≥ 70%

Traditional medicine disease type
Wind wetness heat
Wind cold wetness
type (n = 44)
type (n = 16)
Numbe
Numbe
r of
Percentag
r of
Percentag
patient
e (%)
patient
e (%)
s
s
1
2.3
0
0

43
97.7
16
100.0
p>0.05

Total
(n= 60)
Numbe
r of
Percentag
patient
e (%)
s
1
1.7
59
98.3

Comments: The degree of disease improvement according to Ritchie
index was not different from that according to traditional medicine
disease (p> 0.05).
Table 3.22. Therapeutic effects of traditional medicine disease types
according to DAS28-CRP
Traditional medicine disease type
Wind wetness heat
Wind cold wetness
type (n = 44)
type (n = 16)
Changes in

Numbe
Numbe
DAS28
r
of Percentag r
of Percentag
patient
e (%)
patient
e (%)
s
s
Trung bình
1
2.3
0
0
Tốt
43
97.7
16
100.0
p>0,05

Total
(n= 60)
Numbe
r
of Percentag
patient

e (%)
s
1
1.7
59
98.3

Comments: The degree of disease improvement according to DAS28CRP was not different from that according to traditional medicine (p>
0.05).
Table 3.23. Therapeutic effects of traditional medicine disease types
according to HAQ
Traditional medicine disease type
Wind wetness heat Wind cold wetness
type
type
Change
(n = 44)
(n = 16)
s in
Numbe
Numbe
HAQ
r of
Percentag
r of
Percentag
patient
e (%)
patient
e (%)

s
s
2016
36.4
4
25.0
49%
5028
63.6
12
75.0
69%

17

Total
(n= 60)
Numbe
r of
patient
s

Percentag
e (%)

20

33.3

40

66.7


p>0.05

Comments: The degree of disease improvement according to HAQ
index was not different from that according to traditional medicine (p>
0.05).
- Effective treatment of traditional medicine according to ACR:
Table 3.24. Therapeutic effects of traditional medicine disease types
according to ACR
Changes

20- 49%
50- 69%
≥70%

Traditional medicine disease type
Wind wetness heat
Wind cold wetness
type (n = 44)
type (n = 16)
Number
Number
Percentag
Percentag
of
of patients e (%)
e (%)

patients
0
0
1
6.3
35
79.5
11
68.8
9
20.5
4
25.0
p>0.05

Total
(n= 60)
Number
Percentag
of
e (%)
patients
1
1.7
46
76.7
13
21.7

Comments: The degree of disease improvement according was not different

from that according to traditional medicine (p> 0.05) (p> 0.05).
3.3.6. Unwanted effects of ‘Hoan chi thong’
During the treatment, 2 out of 36 patients (3.4%) felt bloated and 1/36
patients experienced abdominal pain (1.7%) but this unpleasant sensation
was not continuous.
No undesirable effects were recorded based on results of hematological and
biochemical tests before and after the treatment.
CHAPTER 4: DISCUSSION
4.1. Acute toxicity and semi-chronic toxicity of 'Hoan chi thong’
4.1.1. Acute toxicity
The white mice took the maximum dose of the 'Hoan chi thong’ of 61.0g/kg
body weight. This is the maximum amount of medication that rats can
tolerate, therefore, the LD50 of 'Hoan chi thong’ was not determined 'on
white mice by oral route Litchfield-Wilcoxon method at this dose.
4.1.2. Semi-chronic toxicity
The study of semi-chronic toxicity on the experimental rats with 'Hoan chi
thong’ at 4.8g/kg/day (equivalent to the clinical dose for humans and
equivalent to 7 times of the dose for rats) and dose 14.4g/kg/day (3 times the
clinical dose) showed that the medication did not affect the development of
the mice, there were no changes in hematological indicators, blood
biochemistry, and macroscopic morphology and histopathological images

18


of the liver and kidney. This result showed that the 'Hoan chi thong’ is
highly secure.
4.2. The analgesic and anti-inflammatory effects of 'Hoan chi thong’ on
experiment
'Hoan chi thong’ has analgesic effect on pain-induced-by-acetic-acid model,

but this effect is not on the pain-induced-by-temperature model, in other
words 'Hoan chi thong’ has an analgesic effect on the peripheral.
'Hoan chi thong’ has an acute and anti-inflammatory effect. This result is
also consistent with the studies done on the active and anti-inflammatory
effects of each ingredient in the 'Hoan chi thong’ formula according to
modern pharmacology.
The research on individual effects of AAA Tinospora sinensis showed that
the herbal plant has anti-inflammatory, antipyretic effect, it can be used in
the treatment of acute gout, rheumatoid arthritis, pelvic arthritis, etc.
Luteolin in AAA Tinospora sinensis has the effect of inhibiting platelet
aggregation, preventing the formation of blood clots, and improving
circulating flows.
The oil-soluble chemical components in Angelica dahurica have antiinflammatory, analgesic effects, the water-soluble chemical components in
Angelica dahurica has vasoconstrictive and hemostatic effects and muscle
relaxants, and oxypeucedanin hydrate in Angelica dahurica stimulate the
adrenal glands to increase the secretion of ACTH hormone, etc.
The active ingredient polysaccharide in AAA Achyranthes bidentata has
shown the immune modulating effect by regulating the function of
lymphocytes, polymorphonuclear leukocytes, macrophages, erythrocytes
,etc.
The Ethanol in Sargentodoxa cuneata has an anti-inflammatory effect
similar to cyclooxygenase-2 (COX-2), Sargentodoxa cuneata is an
ingredient with strong antioxidant activity that inhibits the formation of free
radicals, the Sargentodoxa cuneata decoction has the effect of regulating
immunity through regulating the activity of natural killer cells, activating the
function lymphocytes that kill or improve the functions of IL-1 elements,
IL-2, IL-3 , etc.
From the results obtained in the study on the anti-inflammatory analgesic
effects of 'Hoan chi thong’ on experiment, we found that 'Hoan chi thong’
has better effects at lower doses. In our opinion, this result is suitable, the

composition contains tannin, which will combine with proteins to form a
covering film and limit the process of the medication absorption in the
stomach and intestine when being used at high doses. This is also a
suggestion for clinicians when prescribing.
4.3. The clinical effects of 'Hoan chi thong’
4.3.1. The analgesic effect of 'Hoan chi thong’

19


- Reducing stiffness time
Joint stiffness is a manifestation of limited movement of the joints. Stiffness
more than 45 minutes is one of the main symptoms that evaluate the disease
progression under ACR.
The research results showed that the average stiffness time in the morning
before the treatment was 46.83 ± 20.66 minutes and after the treatment was
17.17 ± 8.04 minutes. After the treatment with 'Hoan chi thong’, there was a
statistically significant reduction in morning stiffness time (p <0.001), the
average was 30.00 ± 15.12 minutes (table 3.19). 100% of patients decreased
the time of morning stiffness, of which 8.3% of the patients had a decrease
of 20- 49%, 71.7% of the patients had a decrease of 50-69% and 20.0% of
the patients improved by ≥70% (chart 3.2).
- Reducing the number of painful joints
Rheumatoid arthritis is a nonspecific inflammation of the MHD, which is
clinically manifested as painful swollen joints, which leads to hospital
admission. Reducing the number of painful joints is an important criterion to
assess the effectiveness of rheumatoid arthritis treatment.
The research results showed that the number of painful joints before the
treatment was 16.02 ± 5.51 joints and after the treatment was 3.03 ± 2.00
joints. After the treatment, the number of sore joints decreased significantly

(p <0.001), the average was 12.98 ± 4.48 joints. In particular, 100% of the
patients decreased by ≥20%, 6.7% of the patients decreased by 50- 69% and
93.3% of the patients decreased by ≥70%. The results are similar to the
research results of other authors.
- Reducing Ritchie indexes
Along with calculating the average number of painful joints, we also used
the Ritchie Index to assess the pain severity. The research results showed
that after the treatment, the Ritchie index of the patients decreased
significantly (p <0.001), the average was 21.73 ±7.15 points. In particular,
100% of patients decreased by ≥ 20%, 98.3% of the patients decreased by
≥70%, and 1.7% of the patients decreased by 50-69%.
The effect of reducing the Ritchie index of the 'Hoan chi thong’ is similar to
other studies on the effects of some traditional medicine remedies: after the
treatment, the Ritchie index in the studies significantly reduced with p
<0.05-0,001 (Table 4.1).
In this study, the symptoms of swelling, painful, and stiff joints reduced after
the treatment. So in our opinion, the Ritchie improvement is appropriate.
- Reducing pain level through VAS indicators
The results of analgesia (VAS1) and the improvement of disease activity
level (VAS2 and VAS3) are completely consistent with the results of
reducing the stiffness time, the number of painful joints, and the Ritchie
index in the study.

20


The clinical role of 'Hoan chi thong’ is probably due to the chemical
components in the remedy that inhibit the biosynthesis of prostaglandins - a
chemical mediator of the inflammatory response. As a result, the
medicination works to reduce the receptors of the sensory nerve endings

with pain-causing substances of inflammatory reactions such as bradykinin,
histamine, serotonin. Studies have shown that the composition of the 'Hoan
chi thong’ reduces free radicals, oxidation of cell membrane phospholipids
and releases a number of chemical mediators leading to inflammation and
pain. According to traditional medicine, the herbs of Tinospora sinensis,
Gnetum montanum, Angelica dahurica, Achyranthes bidentata,
Cinnamomum, and Sargentodoxa cuneata in the composition of 'Hoan chi
thong’ have effects of removing blood stasis and analgesis. Essential oil in
AAA Cinnamomum has anticonvulsant, analgesic effect; AAA Achyranthes
bidentata has an analgesic effect on mice that have been hurted by the
Koster method; Angelica dahurica has the effect of inhibiting the central
neurosuppression status due to snake venom poisoning, anti-inflammatory
and analgesic effects in experiment. The analgesic effect of the 'Hoan chi
thong’ has also been demonstrated in cramping-induced-by-acetic- acid
model.
4.3.2. The clinical anti-inflammatory effect of ‘'Hoan chi thong’
The anti-inflammatory effect of the clinical 'Hoan chi thong’ is shown to
reduce swelling and reducing subclinical inflammatory indicators.
- Reducing the number of swollen joints
According to the study, the average number of swollen joints was 7.53 ±
4.21 (joints). After the treatment, the number of swollen joints decreased
significantly (p <0.001), the average was 6.36 ± 3.31 (joints). In particular,
100% of patients reduced by ≥20% of the number of swollen joints, of
which 6.7% of the patients decreased by 50-69% and 93.3% of the patients
decreased by ≥70%.
The effect of reducing the number of swollen joints of 'Hoan chi thong’ is
similar to the research results of the following authors: Hoang Thi Que,
Nguyen Thi Thanh Hoa, Nguyen Thi Thanh Tu.
- The decrease in the subclinical inflammatory indicators
The factors that reflect acute inflammatory response include LBP and CRP.

- Rate of blood sedimentation
When the rate of blood sedimentation at the first hour plus half of the rate of
blood sedimentation at the second hour divided by 2 is greater than 10, it is
possible to conclude that the patient is having inflammation. The rate of
sedimentation is of great significance to assess disease activity level and
assessing the therapeutic effects.
According to the study, the rate of LBP was 47.85 ± 24.90 (mm). After the
treatment, LBP significantly decreased (p <0.001), the average was 17.56 ±

21


14.24 (mm). In which, 78.3% of the patients decreased by ≥ 20% of LBP:
63.3% of the patients decreased by 20- 49% and 15.0% of the patients
decreased by 50- 69% (Table 3.26 and chart 3.9).
This is similar to the research results of some other traditional medicine
practitioners such as Hoang Thi Que, Nguyen Thi Thanh Hoa Nguyen Thi
Thanh Tu
- C-reaction protein (CRP)
Along with LBP, CRP is also an important indicator to assess subclinical
inflammation and prognosis. If clinical symptoms reduce but CRP still
increases, the patient needs further treatment.
The results of the study showed that before the treatment the CRP
concentration was 14.35 ± 10.19 mg/dl. After the treatment, the CRP levels
decreased significantly (p <0.001), the average was 4.79 ± 10.00 mg/dl. In
particular, 73.4% of the patients decreased by ≥20% of the CRP, of which
71.7% decreased by 20-49%, and 1.7% of the patients decreased by ≥70%
(Table 3.27 and chart 3.10).
Thus, clinical studies show that 'Hoan chi thong’ has anti-clinical and
subclinical anti-inflammatory effects. This anti-inflammatory effect is also

completely consistent with the experimental results of acute antiinflammatory and chronic anti-inflammatory effects on the experiment of
'Hoan chi thong’.
4.3.3. The effect of reducing the disease activity of 'Hoan chi thong'
The results of clinical studies showed that it is possible to initially identify
that 'Hoan chi thong’ has anti-inflammatory analgesic effect, improves
motor function in patients with rheumatoid arthritis stage I and stage
paragraph II. Farzaei MH et al. (2016) suggested that the traditional
medicine is effective in treating rheumatoid arthritis through a number of
mechanisms such as modulating cytokine precursors such as TNF-α, IL-6
and NF-κB, inhibiting oxidative stress, inhibiting cartilage degeneration
with metalloproteinase destruction, and enhancing antioxidant performance.
The chemical components found in the traditional medicine have different
biological activities including flavonols, lignans, coumarins, terpenes,
glycosyl flavones, dihydroflavonols, phytoestrogens, sesquiterpene lactones,
anthraquinones, alkaloids, and thymoquinones. Based on the structure of the
study, it can be found that the herbs in the 'Hoan chi thong’ contain
flavonoids, which has an antioxidant effect of reducing free radicals,
oxidation of phospholipid layer cell membranes, and reducing the release of
some chemical mediators, thus it has anti-inflammatory and analgesic effect.
4.3.4. The therapeutic effects of ‘Hoan chi thong’ on the traditional
medicine disease types
Dispite the classification of pain due to stasis as presented in the overview,
the symptoms of wind, cold, wetness, heat types, in fact, usually coexist. As

22


a result, most physicians categorize them into two main forms: wind cold
wetness type and wind wetness heat type. The research results showed that
the therapeutic effects according to the Ritchie, DAS28-CRP, HAQ, and

ACR indexes of the wind wetness cold type groups were greater than the
wind wetness heat type group, we have not noticed the difference (p> 0.05).
The cold heat characteristics in the ingradients of ‘Hoan Chi Thuong’
showed that the medicination has neutral charaterisics (Gnetum montanum
and Achyranthes bidentata), warming charaterisics (Angelica dahurica,
Cinnamomum, and Sargentodoxa cuneata and Honey), cooling charaterisics
(Tinospora sinensis) is used in combination, with the effects of dispelling
wind evil, removing dampness, activating blood, activating and smoothing
meridians, tonifying blood qi, and nourishing liver and kidney. So in our
opinion 'Hoan chi thong' can be used with both wind cold wetness type and
wind wetness heat type.
4.3.5. The undesirable effects of ‘complete only system’
The study results showed that after taking 'Hoan chi thong’, 2 out of 36
patients (3.4%) felt floated and 1 out of 36 patients had abdominal pain
(1.7%), however the pain was not continuous.
* Limitations of the research
In addition to the results achieved during the implementation of the project,
our research team found that the content of the thesis also has some
following limitations:
- The new study limits at evaluating and comparing the results before and
after the treatment on a group of patients with rheumatoid arthritis patients
without a control group to compare. This might be less objective when
assessing the effectiveness of researched medication.
- The study has not yet analyzed the relationship between the treatment
results and the stages of the disease, the age and duration of the disease to
clarify the effects of the medicination.
CONCLUSION
1. The acute toxicity (LD50) and the semi-chronic toxicity of ' Hoan chi
thong’ have not been determined on the experimental animals.
- The LD50 of 'Hoan chi thong’ was not determined in white mice at the

dose of 61g/kg body weight (12.7 times of the expected clinical dose).
- 'Hoan chi thong’ at equivalent clinical dose (4.8 g/kg body weight) and 3
times of the oral dose in 4 weeks did not change the weight, hematological,
biochemical, macroscopic morphology, and microscopy of white rats’
kidney and liver.

23


2. 'Hoan chi thong’ has analgesic effect on an external analgesic
mechanism. It has acute anti-inflammatory and chronic antiinflammatory effects on experimental animal models.
- 'Hoan chi thong’ dose 6.8g/kg weight of mice inhibited 34.75 ± 8.45% of
cramping pain on the cramping-caused-by-acetic-acid model compared to
that of the control group (p <0 , 05).
- 'Hoan chi thong’ has anti-inflammatory effect on edema –induced-bycarrageenin mice at 6 o'clock and peritoneal-effusion-by-carrageenin-andformaldehyde model.
- 'Hoan chi thong’ has anti-inflammatory effect. After 7 days, the mice
continued to take the medication at the dose of 6.8g/kg body weight, the
weight of dried granulomatous experiments decreased significantly
compared to the control group drinking distilled water. This effect is
equivalent to prednisolon dose of 5mg/kg.
3. 'Hoan chi thong’ works to treat patients with rheumatoid arthritis
stage 1 and 2.
- The average stiffness time, average number of painful joints, VAS1, VAS2,
VAS3 and average Ritchie after the treatment reduced significantly
compared to that before the treatment.
- The average number of swollen joints, average blood sedimentation rate,
and CRP decreased significantly compared to before the treatment.
- After treatment, the motor function on a scale of HAQ, DAS28-CRP, and
ACR 20 improved significantly compared to before the treatment.
- The degree of disease improvement according to Ritchie index, DAS28 CRP, HAQ and ACR is not different according to traditional medicine (p>

0.05).
- The undesirable effects of 'Hoan chi thong’ are not realized on patients
with clinical rheumatoid arthritis and some subclinical criteria after 28 days
of treatment.
RECOMMENDATIONS
1. 'Hoan chi thong’ in the initial research shows that it is safe and effective
to treat rheumatoid arthritis patients. Therefore, it is advisable to conduct
research with a larger number of patients and in a longer time, and it is
necessary to compare to a control medicine to make it more objective and
scientific.
2. Based on the theory of Traditional Medicine in 'Hoan chi thong’, we can
study the effects of the medication on some other chronic bone and joint
diseases such as osteoarthritis, etc.

24