MINISTRY OF EDUCATION
AND TRAINING
MINISTRY OF HEALTH
HANOI MEDICAL UNIVERSITY
MAI PHUONG THANH
EXPERIMENTAL STUDY ON THE SAFETY AND
EFFECTIVENESS OF TD0014 HARD PILLS
FOR THE TREATMENT OF
MALE SEXUAL DYSFUNCTION
Specialty:
Code:
Pharmacology and Toxicology
62720120
SUMMARY OF DOCTORAL THESIS
HANOI – 2019
The study was completed at:
HANOI MEDICAL UNIVERSITY
Scientific supervisors:
1. Assoc. Prof. Ph.D Pham Thi Van Anh
2. Assoc. Prof. Ph.D Nguyen Trong Thong
Reviewer 1:
Reviewer 2:
Reviewer 3:
The doctoral thesis was publicly defended in front of the University Council at
Hanoi Medical University on
The thesis can be found at:
- National Library of Vietnam
- The Library of Hanoi Medical University
1
INTRODUCTION
Male sexual dysfunction includes disorders of desire, erectile dysfunction,
abnormal ejaculation, orgasmic dysfunction and failure of detumescence; these
conditions may appear alone or in combination with each other. Researching and
seeking drugs for the treatment of male sexual dysfunction originating from
medicinal herbs are of great interest to physicians. TD0014 is a preparation of
herbal medicines which comprises thirty-two medicinal plants and deer velvet. The
composition of TD0014 has several medicinal herbs that have been studied and
used since ancient times in traditional folk medicine as an aphrodisiac. However, no
studies have provided reliable shreds of evidence of their effects on reproductive
functions, or toxicity when combining them in TD0014. Therefore, the study titled
"Experimental study on the safety and effectiveness of TD0014 hard pills for
the treatment of male sexual dysfunction" was carried out to:
1. Determine acute and subchronic toxicity of TD0014 in experimental animals.
2. Evaluate androgenic activity and effects on erectile function of TD0014 in
experimental animals.
3. Evaluate the effects of TD0014 on sodium valproate-induced reproductive
decline in male rats.
Necessity of the thesis
Male sexual dysfunction is a common disorder associated with a wide range of
physical and psychological conditions. Although this disease is not fatal, does not
require emergency management but greatly affects the morale and quality of life of
patients. Research and development of preventive and therapeutic agents for male
sexual dysfunction have been becoming a special concern of world medicine.
Treatment of male sexual dysfunction according to modern medicine is highly
effective in improving symptoms. However, one must be conscientious of its
adverse effects. Following the current trends in medicine, the treatment approach
based on the theory of traditional medicine that has many advantages such as
reducing the economic burden, convenience, friendliness, and fewer side effects has
deployed in many countries around the world, including Vietnam, a country with
long-standing traditional medicine and is considered to have great potential for
medicinal materials in Southeast Asia and in the world with the source of rich and
diverse resources. The widespread use of herbal medicines, nevertheless, requires
scientific verification of their indications and effects by use of modern medical
analysis. Therefore, studies of toxicity and effects of medicinal herbs, herbal
remedies or products derived from medicinal plants such as TD004 which has used
in the market as dietary supplement are necessary, scientific and practical.
New contributions from the thesis
2
TD0014 is a preparation derived from over thirty natural ingredients. When
combining many medicinal ingredients in a preparation, the most worrying issue is
the interaction between the ingredients in the preparation process as well as in the
metabolism in the body, which can increase toxicity, decrease or loss of effects. The
study has shown positive results with high safety and good effectiveness in treating
male sexual dysfunctions of TD0014 hard pills on the experiment, which considered
a new contribution of the thesis. These results are the basis for further preclinical
and clinical trials which will provide the scientific foundation for using TD0014 in
treating male sexual dysfunction.
Tests of androgenic activity have been conducted by a number of domestic
research institutes with a variety of preparations, but mostly on castrated male rats.
Evaluation of the androgenic activity of TD0014 in weanling male rats can also be
considered a new contribution of the thesis.
Thesis outline
The thesis consists of 153 pages, including introduction (2 pages), overview
(44 pages), object and methods of research (12 pages), results (43 pages which
comprises 37 tables, 16 figures, 10 charts), discussion (49 pages), conclusion (2
pages), proposal (1 page). There are 194 English and Vietnamese references.
Chapter 1
OVERVIEW
1.1. Overview of male sexual dysfunction according to modern medicine
Male sexual dysfunction includes disorders of desire, erectile dysfunction,
abnormal ejaculation, orgasmic dysfunction and failure of detumescence; these
conditions may appear alone or in combination with each other. According to
modern medicine, methods used to treat male sexual dysfunction include
testosterone replacement therapy and treatments for one of the most common
symptoms of the disease which is erectile dysfunction.
1.1.1. Testosterone replacement therapy
Testosterone treatment aims to restore testosterone levels to the physiological
range in men with consistently low levels of serum testosterone and associated
symptoms of androgen deficiency. The aim is to improve quality of life, sense of
well-being, sexual function, muscle strength and bone mineral density. Current
testosterone therapies include implants, intramuscular injections, oral formulations,
transdermal delivery systems, transbuccal delivery systems, and intranasal
testosterone.
The risks of testosterone replacement therapy depend on age, life
circumstances and other medical conditions, include exacerbation of prostate
cancer, male breast cancer, worsening benign prostatic hyperplasia, hepatotoxicity
3
and liver tumor, polycythemia, an increased risk of obstructive sleep apnea and
congestive heart failure, infertility, and skin diseases. With these risks, TRT is
contraindicated in men with known or suspected androgen-dependent carcinoma of
the prostate or of the male mammary gland, severe lower urinary tract symptoms
due to benign prostatic hyperplasia, past or present liver tumors, severe chronic
cardiac failure (NYHA IV), severe sleep apnoea, hematocrit > 54%, and male
infertility-active desire to have children.
1.1.2. Drugs for erectile dysfunction
Lifestyle modifications, oral phosphodiesterase-5 (PDE5) inhibitors,
intracorporal injections, topical medication, surgery, vacuum devices, and
acupuncture are some of the treatments available today for erectile dysfunction,
among which PDE inhibitors are the first-line treatment in patients with erectile
dysfunction.
PDE5 inhibitors are indicated for treatment of men with erectile dysfunction,
which is the inability to achieve or maintain a penile erection sufficient for
satisfactory sexual performance. In order for them to be effective, sexual
stimulation is required. There are currently four widely approved PDE5 inhibitors
and are the first choice in treating erectile dysfunction, including sildenafil,
tadalafil, vardenafil, and avanafil; in addition, a number of other PDE5 inhibitors
are licensed in certain countries, such as udenafil and mirodenafil designated in
Korea, or lodenafil used in Brazil. All PDE5 inhibitors are contraindicated in
patients with a known hypersensitivity to any component of the agents; patients
who are taking any form of organic nitrates, regularly or intermittently; patients
who have loss of vision in one eye because of non-arteritic anterior ischaemic optic
neuropathy (NAION), regardless of whether this episode was in connection or not
with previous PDE5 inhibitor exposure. They should not be used in men for whom
sexual activity is inadvisable (e.g. patients with severe cardiovascular disorders
such as unstable angina or severe cardiac failure), severe hepatic impairment,
hypotension (blood pressure < 90/50 mmHg), recent history of stroke or myocardial
infarction and known hereditary degenerative retinal disorders such as retinitis
pigmentosa (a minority of these patients have genetic disorders of retinal
phosphodiesterases).
1.2. Overview of the mode of action of medicinal herbs for male sexual
dysfunction
A great number of traditional herbal medicine have been used to treat male
sexual dysfunction, especially erectile dysfunction, applied singly or in the form of
compound formulas. Most of the herbal remedies are used empirically and thereby
are not convincing. In this condition, many studies are being conducted to
investigate the underlying mechanism of those herbs using modern biotechnology.