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All[Minoxidil Solution] It's a paper on minoxidil..
Male Hair Loss and Minoxidil / Dr. Hideo Uno
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Wisconsin Regional Primate Research Center 고문
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Assistant Professor of Clinical Pathology at the University of Wisconsin
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Participation as a responsible researcher in research/development of minoxidil sanctions by business partners
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Male Hair Loss and Minoxidil et al. Publish Many Papers
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▷ Summary
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▷ the beginning
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1. Morpho (毛包) Changes in Men's Hair Loss
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2. Effects of Minoxidil on Hair Loss Treatment
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3. 대해 About other drugs
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4. Anti-Androgen and Prevention of Hair Loss in Monkeys
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5. Comprehensive
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Dermatology MOOK No.19
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a 毛包 zygomatic disease
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Published January 10, 1993
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Summary
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Male-type hair loss is not caused by pathological changes accompanied by follicular degeneration or inflammation, but by the gradual decrease of large hairs (毛包) on the scalp by androgen, which increases after puberty in people with genetic factors. These miniaturized foams (毛包) continue to have a mother cycle (毛周期) for a considerable period of time thereafter. The hair cycle (毛周期) is the ability of the hair follicle (毛包) to denature over a certain period of time and to make new hair follicles (毛包), and it is because of this that the hair is lost and newly created. In the development of sexual 毛 or 毛症 caused by drugs, the new hair follicle (毛包) is larger and thicker by the mother cycle (毛周期), but the opposite phenomenon is the substance of male hair loss. Therefore, if this process can be stopped or if the hair growth (軟毛) can be returned to the seed growth (終毛) using a drug that causes polymyelosis, it will help prevent and treat hair loss.
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Minoxidil, originally used as a hypertension drug in the 1980s, showed serious side effects of polymorphism, and began experimenting with it as a male hair loss treatment. Using experimental monkeys for male hair loss, I confirmed that minoxidil acts to increase the 毛包 of the hair loss part. The action was due to the increase in the growth rate of subcellular (芽細胞) in the follicle (毛包) when the follicle (毛包) enters a new growth phase. As long as the follicle (毛包) maintains the parental cycle (毛周期), the follicle (毛包) can be increased or reduced by drugs or hormones. However, in the long-running hair loss area, the hair follicle (毛包) is extremely contracted and deposited, so it can be said that it is almost impossible to lose the hair cycle (毛周期).
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In addition to the principle of action of minoxidil, prevention of hair loss by antiandrogen drugs and treatment using diazoxide have been confirmed through experiments with monkeys, so we will introduce them together.
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the beginning
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A phenomenon in which the face or 軟毛 of the body increases is called polymyelosis. This is often seen in side effects such as various drugs, especially hypertension drugs, hormones, and herbal medicines that must be taken for a long time. Interested in the fact that a drug that induces blood pressure drop using peripheral vasodilation called minoxidil frequently causes polymyelosis, an experiment has been actively conducted in the United States for 10 years to change hair that is becoming 軟毛, a male hair loss. After 3-4 months, thick and dark hair began to appear as a result of continuous application to the frontal part of hair loss in male hair loss patients or experimental monkeys by changing what was originally an internal medicine to a topical application. In humans, it was particularly effective for early hair loss and circular hair loss at the end of the head.
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This miraculous phenomenon, "Hair loss is cured," could sufficiently surprise not only the medical community but also the general society. However, for medical researchers like me, this phenomenon is an important task to clarify the source of male hair loss, increase the effectiveness of the drug, and confirm the stability of long-term use. I have been studying the frontal hair loss of monkeys living in Southeast Asia and China, and since this hair loss is similar to the male hair loss of humans in various ways, I used this monkey to examine the treatment effect of minoxidil, especially the process of increasing 毛包, to observe its action. In this chapter, we will first explain how 毛包 changes in the process of male hair loss over time and the clinical effects of minoxidil. Finally, the process of increasing the 毛包 of minoxidil using monkeys, its action point, and the possibility of preventing occurrence using antiandrogen drugs will be described.
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Figure 1. Comparison of hair follicles (毛包) between male hair loss and normal hair loss
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The hair follicle (毛包) in the hair loss area is small compared to normal. The seed hairs (終毛) fur (毛包) (thick arrow) and the soft hairs (軟毛) fur (毛包) (thin arrow) in the growing season. Hair (軟毛) Fur (毛包) in Rest Period
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Table 1. Density of scalp inner foam (毛包) by age
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1. a 毛包 change in male hair loss
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This hair loss is generally classified as non-irradiated hair loss, and at least there is no inflammation or degeneration of the 毛包 (fog) or surrounding skin tissue. It is a phenomenon in which the hair is not completely lost, but the seed hair (終毛) gradually becomes thinner and shorter and eventually turns into a haze (軟毛). Histologically, if you look at the hair follicle (毛包), the hair follicle (毛包) in the hair loss area is extremely short and generally reduced compared to the long hair (終毛) in the normal scalp.(Figure 1) This small 毛包 is no different from large 毛包 in form and maintains a clear mother cycle (毛周期) by mixing growth 期毛 and resting 休止期毛. Therefore, it is a consensus at this point that the substance of this male-type hair loss is the reduction of the hair follicle (毛包). In addition, most of these soft hair (軟毛) 毛包 are resting hair (休止期毛), and growth hair (期毛) remains less than 30% of the total. This was the same in the soft hair (軟毛) scalp of monkeys. On the other hand, in the scalp covered with long normal hair, most of the follicles (毛包) (70% or more) are growth 期毛. As a result, the reduced follicle (毛包) does not produce hair only for a fairly short period of time, so it is thought that it stops with a resting period afterwards. In other words, only short hair (軟毛) can be produced and it has the characteristic of maintaining such hair (軟毛) for a long time.
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On the other hand, the question of whether the phenomenon of hair loss is simply due to the contraction of the hair follicle (毛包) or whether the number decreases due to the loss of the hair follicle (毛包) has continued for a long time. At first glance, there is also a report comparing scalp hair follicles (毛包) of advanced male hair loss patients who appear to have complete hair loss with young people or their peers who do not have hair loss symptoms. First of all, it was found that the number of hair follicles (毛包) was clearly reduced in male-type hair loss. The number of hair loss follicles (毛包) after the age of 70 was almost halved compared to the same age without hair loss. As a result of my observation of the scalp of an elderly person who has been suffering from long-term hair loss, it was confirmed that the follicle (毛包) is degenerated and does not exhibit periodic proliferative capacity.
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Figure 2. 70-year-old man's scalp hair loss
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Morpho (毛包) is highly regressing. There is no hair and no growth symptoms appear.
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In this case, no treatment is effective, and it is also clear from this point of view that treatment by minoxidil is effective for relatively early hair loss.
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As such, male hair loss is not a pathological phenomenon, but rather a gradual reduction as the 毛包 of the scalp repeats the cycle due to the rise of testosterone in the blood and genetic factors that cause hair loss. Therefore, if the number of subcellular (芽細胞) groups is increased by selectively stimulating the subcellular (芽細胞) that makes new follicles (毛包) when the current resting follicles (毛包) change to the growth phase, the new growth period (毛包) will be expanded than before. Minoxidil can be said to be a drug that selectively has these effects. Of course, this effect is recognized not only as a hair follicle (軟毛) of hair loss, but also as a hair follicle (軟毛) of the entire body becomes thicker.
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2. Effect of Minoxidil on Hair Loss Treatment
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(1) a human clinical trial
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It has been four to five years since minoxidil was used as a prescription drug in Canada, the United States, and Europe, but it remains the same now that it is effective in early hair loss patients, especially at the tip of the head. In 1987, clinical effects of minoxidil, used as an experimental drug in various parts of the United States, on male hair loss patients were reported. De Villez states that there is no significant difference in the 2% and 3% solutions. The effectiveness rate varies greatly depending on the type of hair loss, but it is considered to be the limit of the effect around 40%. However, in terms of safety, the occurrence of primary irritating dermatitis (7.5%) and allergic contact dermatitis (3.7%) has recently been reported at a rather high rate in the UK.
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(2) Effects of monkey frontal hair loss and minoxidil
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Figure 3. Increased hair growth and 毛包 by minoxidil
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The forehead of a 4-year-old male monkey is an early alopecia with rather long hair (軟毛). Three months after applying the 5% solution, it changed to seed hair (終毛), and after that, it was continuously used to maintain seed hair (終毛) and the overall hair is getting thicker. However, within 3 months of discontinuation, the seed hair (終毛) was lost and returned to hair loss. Polliculogram is hair loss type before use and all are short. After application, the resting follicle (毛包) transitioned to the growth phase and grew.
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Experimental monkeys with male hair loss symptoms have been introduced by several people, including me, but the emergence of minoxidil has increased their usefulness. After puberty, the monkey's frontal brain gradually changes into a soft hair (軟毛) at a time when testosterone in the blood rises. If you apply minoxidil (5% solution) to this frontal head every day, you can see that the 軟毛 has changed to 終毛 even with the naked eye about three months later. This process was observed as a continuous tissue section of the biological skin, and the period and length of each follicle (毛包) were shown as an analysis diagram, and the pattern was reviewed as one before and after treatment. As shown in Figure 3, the frontal head before treatment is a typical alopecia appearance, and the foliculogram is mostly hair follicles (毛包) in short resting periods, and although there are sometimes growth periods, it is about half the length of normal hair (終毛) hair follicles (毛包). Like male hair loss in humans, most of the monkey's hair loss was resting hair (軟毛) and hair loss (毛包). Meanwhile, three months after applying minoxidil, the frontal head began to show thick and long bell hairs (終毛) almost all over it. More than half of the foliculogram at this time was in the growth period, and all of them were significantly longer than before treatment, including the resting period. If the treatment was continued, the hair of the frontal head became darker and longer, and the length of the fur (毛包) was even longer than three months ago. However, when the treatment was stopped here, the hair on the frontal head soon turned back into thin and short hair (軟毛). At the same time, both the length of the morpho (毛包) and the distribution of the morpho (毛周期) returned to the pre-treatment period. From these facts, it was found that it was necessary to continuously administer minoxidil in order to maintain the increase in 毛包.
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Figure 4. The growth cycle of 毛包 and the foliculogram
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After basic drugs and minoxidil external application, resting hair (軟毛) and hair follicles (毛包) in the hair loss area are changed to growth hair follicles (毛包) and become a resting type in the next cycle. This is in contrast to the followulogram. Arrows of different sizes, the end of the arrow indicates the corresponding morpho (毛包). Minoxidil clearly leads the increase in the morpho (毛包) to the early stages (A2, A3) of the growth period and makes larger morpho (毛包) (A4, A5-6) and maintains its size in the regression period (C) and rest period (T).
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In other words, Figure 4 shows the process of increasing the haze (軟毛) fur (毛包) by minoxidil. When the hair follicle (毛包) of the hair loss part transitions from rest period to another cycle, the hair follicle (毛包) epithelial cell group, which is close to the base of the hair follicle (毛包), is first proliferated and integrated, and at the same time, the hair follicle (毛包) epithelial cell group grows in the form of germination. After that, the epithelial cell group continues to proliferate and differentiates into the hair roots and internal and external hair roots of the future growth 期毛 (毛包). New hair is already made in the follicles (毛包) of this period. The new follicle (毛包) gradually grows toward the subcutaneous layer, and the new hair grows toward the skin surface layer, eventually reaching the old follicle (毛包) wall, and travels through the same pores with the old hair maintained by this old resting follicle (毛包). During this period, the two old and new hairs come out of the same pores. Eventually, the old follicle (毛包) wall changes into part of the new wall, and the old hair falls out (natural hair). The new growth 期毛 毛包 maintains its shape and function (hair production) for a certain period of time thereafter. It is natural that the longer the fur (毛包) this period, the longer the hair produced. On the other hand, the end of the proliferation period is subject to natural quenching (self-digestion of cells, proliferation of outer connective tissue cells in the follicle (毛包), and removal of modified cell fragments due to its prophylaxis) under the follicle (毛包). This is a process that leaves no trace at all after denaturation and disappearance of the follicular tissue, and this period is called the regression period.(Fig. 4, C) However, the hair follicle (毛包) is not completely lost at this time, but the upper part of the hair remains rather than the solar root, and the hair definitely adheres to the hair (毛包) wall cells. This fur cloth (毛包) is a resting period (Figure 4, T), and the hair made of the pre-degenerative fur (毛包) is maintained by the resting cloth (毛包). It is the mother cycle (毛周期) that this resting hair follicle (毛包) also enters the growth phase by repeating the same method, and each hair follicle (毛包) repeats this cycle endlessly throughout its life, starting with the skin of the birth.
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Figure 5. H-Timinjin's entry into Morpo (毛包)
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Comparison of base group (a, b) and minoxidil group (c-f)
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In terms of follicles (毛包) in the early stages of growth, thymidine entry (arrow) is higher than that of the latter, and it is also inhaled into dermal papillae. (DP) DP : Breast head, H : Hair in resting hair (毛包), h : Hair in new growth hair (毛包), ES : Appearance root
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On the other hand, if we go back to Figure 4 and look at the process of turning 軟毛 into 終毛 by minoxidil, we can see that when resting follicles (毛包) are converted into growth phase, the proliferation of subcellular (芽細胞) or neoplasm (毛包) 毛包 occurs actively. At this time, if minoxidil increases the division growth rate of these cells and increases the number of new cells, it is natural that the new growth follicles (毛包) become larger than the control group. This is also evident in the feton change of the polliculogram. Looking at this phenomenon using thymygene labeled as a radioisotope in terms of DNA synthesis, as shown in Figure 5(a, c, e), the follicles (毛包) (early growth phase, c) of the scalp treated with minoxidil have a larger portion of germination and a much larger number of labeled cells than the same-shaped follicles (毛包) (a) of the control group. DNA synthesis appeared in almost every part of the growing follicle (毛包) (e), as well as in the subcellular (芽細胞) of the follicle (毛包) (e) in the early stages of growth. As such, it was discovered that minoxidil promotes cell division that rapidly proliferates and differentiates in growth hair follicles (毛包).
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In this way, the phenomenon that the resting hair follicle (毛包) of the hair (軟毛) enters a new growth period was also shown in the existing drug group (藥劑群), but in this case, the size of the growth hair follicle (毛包) was no different from before treatment (毛包) hair follicle (軟毛). On the other hand, it has already been mentioned that it takes about three months for the monkey's morpho (毛包) to transition from rest to full growth. Therefore, it can be seen that after applying minoxidil, it takes more than 3 months for the soft hair (軟毛) to be changed to 終毛. It takes approximately 3-4 months for humans as well. When the treatment is stopped, the seed mother (終毛) returns to the hair 軟毛, but by repeating the treatment, the seed mother (終毛) is changed to the seed mother (終毛). For example, the effect of minoxidil is large for rather long hair (軟毛), and the 2% solution is slightly weaker than the 5% solution, but it has been clearly confirmed that it has a hair growth effect.
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(3) Principle of Action of Minoxidil
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In the transdermal absorption (俓皮吸收) of minoxidil, a study using radioisotopes on human hair loss showed that the detection rate in subcutaneous tissue was extremely low. An average of 2.5% is discharged through urination, and most of them (40% or more) remain on the skin surface layer. When I applied it to the topical area using a monkey and periodically collected blood to examine the blood concentration, the values were almost the same for 2, 6, 15, and 24 hours. However, there seems to be no evidence that minoxidil absorbed subcutaneously is selectively accepted by morpho (毛包). In addition, it has been found that minoxidil does not occur immediately after administration of blood pressure, but mainly changes to minoxidil·sulfotransferase in the liver, indicating a strong vasodilation effect. To find out whether these metabolism also occurs in skin tissue, I investigated the activity of the scalp epithelium, follicle (毛包), and minoxidil sulfotransferase of connective tissue in monkeys and found that the follicle (毛包) has most of the activity (about 60% or more). However, it cannot be denied that minoxidil not only acts directly on the follicles (毛包) but also causes the expansion of subcutaneous blood vessels is affecting the proliferation of 毛包 cells. As such, the reality of the action of increasing the 毛包 of minoxidil is not yet known. However, no noticeable systemic side effects have been reported yet after long-term (5 years) administration of minoxidil in the local area of humans or monkeys.
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3. About other drugs
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In addition to minoxidil, drugs with hematopoiesis as side effects are also available. Miwa et al. recently synthesized clinical observations of polymyelosis caused by various drugs. All of these drugs require long-term use, and are known as minoxidil, diazoxide, cyclosporine, psoralens, phenothiazines, phenytoin, and oral contraceptives. Among them, the author confirmed that it is effective in diazoxide (5% solution) prepared for local application to monkey hair loss. In addition, the fact that testosterone, which rises in the blood after puberty, plays a major role in the expression of genetic factors for male hair loss is considered certain in both humans and monkeys, and next, an experimental example using antiandrogen will be explained.
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Figure 6.5 Monkeys in α-reductase inhibitors
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Effect on the amount of hair in the unit area of the frontal head
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Both groups have fluctuations, but the amount is gradually decreasing in the base group.
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4. Anti-Androgen and Prevention of Hair Loss in Monkeys
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Anti-androgenic agents generally engage in androgenic activity within cells and interfere with intrinsic androgen action. However, with regard to prostate and follicle (毛包), testosterone enters the cell and then changes to DHT by 5α-reductase, which binds to androgen receptors in the nucleus and begins to act as male hormones. This is also evident in the fact that the pseudotropic sound that occurs in a genetically solid family of 5α-reductase represents the prostate after puberty, a thin beard, and loses the temporal process of hair.
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In this way, if the activity of 5α-reductase can be prevented in the morpho (毛包), the action of androgen can be suppressed in the development of whiskers or male hair loss. Of course, binding antagonists to androgen receptors would be effective, but this is rather dangerous. This is because androgen not only acts as a sex hormone, but also promotes the development of muscles and bones. At least the current androgen receptor is thought to be the same in any tissue, and if the antagonist affects tissues other than the morpho (毛包), it inhibits metabolism such as bones and muscles. Therefore, if a 5α-reductase inhibitor is locally administered to treat hair loss and androgen action is prevented only in morpho (毛包), it is considered the best way to suppress side effects.
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As a result of continuous use of a 5α-reductase inhibitor called 4-MA for about two years in the monkey's frontal brain before puberty, the target group showed natural hair loss, but the drug group (藥劑群) showed suppression of hair loss. This was revealed by the comparison of changes in hair weight and foliculogram in the scalp unit area.(Figures 6, 7) However, 5α-reductase activity in the scalp was also significantly reduced in the drug group. In the fundamental treatment of hair loss, inhibition of androgen action in morpho (毛包) is the most effective. However, we have to think about the whole body of androgen, its effects on genital organs, nerve tissues, bones, and muscle tissues. On the other hand, there are reports that hair loss treatment effects have been obtained by simultaneously using minoxidil and antiandrogen drugs.
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In addition, as a result of using a mixture of retinoids and minoxidil in male hair loss patients, there are reports that the hair growth effect was significantly lower than when minoxidil was used alone.
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5. Comprehensive
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Through these studies, it was found that the thickening of hair in a part of the body or the thickening of hair in the hair loss area is caused by an increase in the foaming (毛包). If the growth base foam (毛包) that produces hair is large, the hair is thick, has a high pigment content, and generally produces long hair. The follicles (毛包) in the growth phase are composed of cell groups with different forms or differentiation. In particular, in the parent part, as shown in Figure 8, there are cells that make internal and external hair root centered on the cells that become the hair itself. These cell populations proliferate at the bottom of the pore area and then begin to differentiate by arranging them on a specific side. In the innermost part of the pore, there is a mother papilla surrounded by these follicle (毛包) cells and the base is continuous with the connective weft.
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Figure 7. Anti-androgen anti-hair loss prevention effect
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The foliculogram shows a slope pattern in both groups before use. After two years, the base group changed to a typical hair loss type, but the feton has not changed in the drug group.
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Figure 8. Tissue image near the 毛包 of the hair follicle (毛包) during the growing season
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In the center, there is a concentration of pre- and post-keratotic cells (Hm) and post-keratotic cells (Hc), surrounding him with endochromatic root (IRS), appearance root (ERS), and basilar membrane (BM). In the lower part of the mother, there are a number of dividing cells (arrows), and pigment cells (Mc) approaching the mother papilla wall. The shape of the arrow indicates layered differentiation of the mother cell.
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As such, it is difficult to think that growth-phase follicles (毛包) composed of differentiated or differentiated cell groups grow on their own. Therefore, as mentioned repeatedly so far, it seems that there is no opportunity for the soft hair (軟毛) fur (毛包) to change into a large seed hair (終毛) fur (毛包) fur (毛包) except when it enters the growth period from the rest period. At that time, the proliferation function of 芽細胞, which was latent at the base of this resting hair follicle (毛包) or at the attachment of the mouth root, is affected by hormones or drugs. On the other hand, it has been known for a long time that hair follicle cells have the ability to induce follicle (毛包) formation, and recently, this cell was distinguished from other pre-infrared (芽細胞) groups by cell culture, and the induction of the creation of follicles (毛包) by cultured papillae was also confirmed. In addition, these dermal papillae exhibited 5α-redactase activity proportional to the expression of androgen sensitivity of the morpho (毛包). As described above, it is important to select a specific cell group of these follicles (毛包) to examine the expression of induction or differentiation in future studies on hormone receptors, genes, and drugs of follicles (毛包).
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The contents of this post are based on the user's personal experience and public general information, and are not intended to advertise, promote, or encourage the use of certain medicines. Please consult a medical professional for the use of prescription drugs and treatment.
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