What Is Minoxidil?

Minoxidil, chemical name 6- (1-piperidinyl) -2,4-pyrimidinediamine, 3-oxide, is a white or off-white crystalline powder. Slightly soluble in ethanol, slightly soluble in chloroform or water, very slightly soluble in acetone; soluble in glacial acetic acid. Clinically, as an opener of potassium ion channels, it can directly relax vascular smooth muscle and have a strong arteriolar dilatation effect, which reduces peripheral resistance and blood pressure, but has no effect on the volume vessels, so it can promote venous reflux. At the same time, due to reflex regulation and positive frequency effects, cardiac output and heart rate can be increased without causing orthostatic hypotension.

Minoxidil, chemical name 6- (1-piperidinyl) -2,4-pyrimidinediamine, 3-oxide, is a white or off-white crystalline powder. Slightly soluble in ethanol, slightly soluble in chloroform or water, very slightly soluble in acetone; soluble in glacial acetic acid. Clinically, as an opener of potassium ion channels, it can directly relax vascular smooth muscle and have a strong arteriolar dilatation effect, which reduces peripheral resistance and blood pressure, but has no effect on the volume vessels, so it can promote venous reflux. At the same time, due to reflex regulation and positive frequency effects, cardiac output and heart rate can be increased without causing orthostatic hypotension.

Chinese name

Minoxidil

Foreign name

minoxidil

CAS number

38304-91-5

Chemical formula

C9H15N5O

EINECS number

253-874-2

Melting point

272-274 ° C

Security description

26-36-45-36 / 37 / 39-22

Danger symbol

Xn, T +

Minoxidil Compounds

Minoxidil Basic Information

Chinese name: Minoxidil

Chinese alias: 6- (1-piperidinyl) -2,4-pyrimidinediamine-3-oxide; Changwending; Minoridine;

English name: minoxidil

English alias: Regaine; 2,4-diamino-6-piperidino-pyrimidine-3-oxide; 2,6-Diamino-4-piperidinopyrimidine 1-Oxide; Rogaine; Minoxidil; Theroxidil; 3-hydroxy-2-imino-6- piperidin-1-ylpyrimidin-4-amine; Tricoxidil; 6- (1-Piperidinyl) -2,4-pyrimidinediamine 3-oxide 6- (1-Piperidinyl) pyrimidine-2,4-diamine 3-oxide; Lonolox; 6- (1-Piperidinyl) -2,4-pyrimidinediamine 3-oxide (6- (1-Piperidinyl) pyrimidine-2,4-diamine 3-oxide; 2,6-Diamino-4- (piperidin-1-yl) pyrimidine 1 -oxide; Alostil; Loniten; Minoximen;

CAS number: 38304-91-5

MDL number: MFCD00063409

EINECS number: 253-874-2

RTECS number: UV8200000

PubChem number: 24277853

Molecular formula: C ₉ H ₁₅ N ₅ O

Structural formula:

Molecular weight: 209.24800

Exact mass: 209.12800

PSA: 91.16000

LogP: 0.91830

Minoxidil physical and chemical properties

Appearance and properties: white crystalline powder

Density: 1.52 g / cm ³

Melting point: 272-274 ° C (dec.) (Lit.)

Boiling point: 351.7ºC at 760 mmHg

Flash point: 166.5ºC

Refractive index: 1.724

Stability: Stable at normal temperatures and pressures.

Storage conditions: Keep in a cool, dry location. Keep containers closed when not in use. Protect from light.

Minoxidil Safety Information

Customs code: 2933990090

WGK Germany: 3

Danger category code: R22; R36 / 37/38

Safety instructions: S26-S36

RTECS number: UV8200000

Dangerous goods mark: Xn ^[1]

Minoxidil calculated chemical data

1. Hydrophobic parameter calculation reference value (XlogP): None

2.Number of hydrogen-bonded donors: 3

3.Number of hydrogen bond acceptors: 3

4.Number of rotatable chemical bonds: 1

5.Number of tautomers: 4

6. Topological molecular polar surface area 88.9

7.Number of heavy atoms: 15

8.Surface charge: 0

9.Complexity: 329

10.Number of isotope atoms: 0

11. Determine the number of atomic stereocenters: 0

12. Uncertain number of atomic stereocenters: 0

13. Determine the number of chemical bond stereocenters: 0

14. Uncertain number of chemical bond stereocenters: 0

15. Number of covalent bond units: 1 ^[2]

Minoxidil synthesis method

4-Chloro-2,6-diaminopyrimidine (see 08910) is obtained from methyl cyanoacetate through cyclization and chlorination, and then oxidized with perbenzoic acid to obtain 6-amino-1,2-dihydro-1- Hydroxy-2-imino-4-chloropyrimidine (C4H5CIN4O), and finally condensed with hexahydropyridine to obtain mentlopidine. ^[2]

Minoxidil uses

Antihypertensive drugs for refractory, essential or renal hypertension. For the prevention of oily hair loss and animal husbandry ^[2]

Minoxidil Pharmacopoeia Standard

Minoxidil source (name), content (potency)

This product is 6- (1-piperidinyl) -2,4-pyrimidinediamine, 3-oxide. Calculated on dry basis, containing C9H15N5O shall not be less than 99.0%.

Minoxidil traits

This product is white or off-white crystalline powder.

This product is slightly soluble in ethanol, slightly soluble in chloroform or water, very slightly soluble in acetone, and soluble in glacial acetic acid.

Minoxidil identification

(1) Take this product, add ethanol to dissolve and dilute it to make a solution containing about 6g per 1ml. According to UV-Vis spectrophotometry (Appendix IVA of Pharmacopoeia Part II of 2010 edition), it has a maximum absorption at 231nm.

(2) The infrared light absorption spectrum of this product should be the same as that of the control ("Infrared Spectra of Drugs" 608).

Minoxidil inspection

Chlorinated compounds

Take about 20mg of this product, accurately weigh it, and perform organic destruction according to the oxygen bottle combustion method (Appendix C of the second edition of the Pharmacopoeia 2010), and use 10ml of 0.1mol / L sodium hydroxide solution as the absorption solution. After the radon is burned, shake it vigorously. For a few minutes, rinse the stopper and platinum wire with a small amount of water, and wash the liquid into the absorbent solution. Move the absorbent solution into a 50ml Nass colorimetric tube and inspect it according to the chloride inspection method (Appendix A of Part Two of the 2010 Pharmacopoeia). Compared with the control solution (same operation as the test product, but the test paper is not included in the filter paper when burning, and 4.0ml of standard sodium chloride solution is added), it must not be more concentrated (0.2%).

relative substance

Take an appropriate amount of this product, accurately weigh it, add the mobile phase to dissolve and dilute it to make a solution containing about 0.25mg per 1ml, as the test solution; take an appropriate amount, use the mobile phase to quantitatively dilute it to make about 1ml. A 2.5 g solution was used as a control solution. According to high performance liquid chromatography (2010 edition Pharmacopoeia Part II Appendix VD) test. Octadecylsilane-bonded silica gel as filler; methanol-water-glacial acetic acid (70: 30: 1) (each 1000ml contains 3.0 g of sodium sulfosuccinate dioctyl ester, and pH is adjusted with perchloric acid Value to 3.0) is the mobile phase; the detection wavelength is 240nm. Take an appropriate amount of this product and medroxyprogesterone acetate, add the mobile phase to dissolve and dilute it to make a mixed solution containing about 0.25mg per 1ml, take 10l, inject the liquid chromatograph, record the chromatogram, and count the theoretical plate number The calculation of nodil peak is not less than 2000, and the resolution of minoxidil and medroxyprogesterone acetate peak should be greater than 2.0. Precisely measure 10 l of the control solution, and inject it into the liquid chromatograph. Adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 20% of the full scale. For a phase chromatograph, record the chromatogram to twice the retention time of the main component peak. If there is an impurity peak in the chromatogram of the test solution, the sum of the area of each impurity peak must not be greater than the main peak area (1.0%) of the control solution.

Loss on drying

Take this product and dry it to constant weight at 105 ° C, and the weight loss shall not exceed 0.5% (Appendix L of Pharmacopoeia Part II of 2010 Edition).

Residue on ignition

Take 1.0g of this product and check it according to law (Appendix N of Part Two of the 2010 Pharmacopoeia). The residual residue shall not exceed 0.15%.

Heavy metal

Take the residue left under the item of burning residue and check it according to law (Appendix H of the second edition of the Pharmacopoeia of 2010 Edition, the second method H), the content of heavy metals must not exceed 20 parts per million.

Determination of Minoxidil

Take about 0.15g of this product, accurately weigh, add 50ml of glacial acetic acid, dissolve at a slight temperature, titrate by potentiometric titration (Appendix 2010 A of the second edition of the Pharmacopoeia, 2010 edition), titrate with perchloric acid titration solution (0.1mol / L), and The results of the titration were corrected with a blank test. Each 1ml of perchloric acid titration solution (0.1mol / L) is equivalent to 20.93mg of C9H15N5O. ^[3]

Minoxidil method

Method name: Minoxidil API-Determination of Minoxidil-Non-aqueous titration

Scope of application: This method uses the titration method to determine the content of minoxidil in minoxidil.

This method is applicable to minoxidil APIs.

Principle of the method: add glacial acetic acid and crystal violet indicator solution to the test sample, titrate the solution with perchloric acid until the solution turns blue-green, and correct the titration result with a blank test. Calculate the minoxidil based on the amount of titrant used content.

Reagent:

Glacial acetic acid

Perchloric acid titrant (0.1mol / L)

Crystal violet indicator liquid

Reference potassium hydrogen phthalate

Sample preparation: 1. Perchloric acid titration solution (0.1mol / L)

Preparation: Take 750mL of anhydrous glacial acetic acid (calculated with water content, add 5.22mL of acetic anhydride per 1g of water), add 8.5mL of perchloric acid (70 ~ 72%), shake well, let cool, add an appropriate amount of anhydrous glacial acetic acid to make 1000mL, shake well and leave for 24 hours. If the test sample is easily acetylated, the water content of the solution must be determined by the moisture measurement method, and then the water content of the solution is adjusted to 0.01% ~ 0.2% with water and acetic anhydride.

Calibration: Take about 0.16g of standard potassium hydrogen phthalate dried to constant weight at 105 , accurately weigh, add 20mL of anhydrous glacial acetic acid to dissolve, add 1 drop of crystal violet indicator solution, and slowly titrate with this solution to Blue, and the titration results are corrected with a blank test. Each 1mL of perchloric acid titration solution (0.1mol / L) is equivalent to 20.42mg of potassium hydrogen phthalate. Calculate the concentration of this solution based on the consumption of this solution and the amount of potassium hydrogen phthalate taken.

Crystal violet indicator liquid

Take 0.5 g of crystal violet and add 100 mL of glacial acetic acid to dissolve.

Operation steps: accurately weigh about 0.2g of the test sample, add 10mL of glacial acetic acid and 1 drop of crystal violet indicator solution, titrate with perchloric acid titrant (0.1mol / L) until the solution is blue-green, and use the titration result with Blank test correction. Each 1mL of perchloric acid titration solution (0.1mol / L) is equivalent to 20.93mg of C9H15N5O.

Note: "Precision weighing" means that the weighed weight should be accurate to one thousandth of the weighed weight. "Precision measurement" means that the accuracy of measuring the volume should meet the accuracy requirements of the volume pipette in national standards. ^[4]

Minoxidil Pharmacology and Toxicology:

Minoxidil directly dilates the arterioles, thereby lowering blood pressure, but the specific mechanism is unknown. This product does not dilate the small veins. Reduced peripheral vascular resistance leads to increased reflex heart rate and increased cardiac output. Renal activity increases after hypotension, causing water and sodium retention. This product does not interfere with vascular motion reflex, so no orthostatic hypotension occurs. ^[5]

Minoxidil pharmacokinetics:

Easy to absorb by mouth (up to 90%). This product does not bind to plasma proteins. The drug concentration in the blood peaked at 1 hour after the administration, and then decreased rapidly thereafter. Plasma t1 / 2 ranged from 2.8 to 4.2 hours and remained unchanged during renal dysfunction. However, the antihypertensive effect has no corresponding relationship with the blood minoxidil concentration. Antihypertensive effect begins within 1.5 hours after a single oral dose. The maximum antihypertensive effect occurs 2 to 3 hours after administration. The antihypertensive effect can last for 24 hours or longer (up to 75 hours), which may be stored in the arteries longer than Vascular smooth muscle. It is metabolized in the liver, and its metabolite glucuronide conjugate can be excreted with urine. 3% are excreted from feces. This product can be removed during dialysis. ^[5]

Minoxidil indication

Severe or refractory hypertension and renal hypertension have a stronger antihypertensive effect than hydrazidine. It does not cause orthostatic hypotension, and there is no decrease in efficacy after long-term use. Combined with Punelol and other synergistic effects, and can offset the adverse reactions of the two. Topical for scarring alopecia (alopecia areata) in men. ^[6]

Minoxidil contraindications:

Use this product with caution when: cerebrovascular disease, non-hypertensive heart failure, coronary heart disease, angina pectoris, myocardial infarction, pericardial effusion, pheochromocytoma, and renal dysfunction.

Minoxidil Dosage:

1. Commonly used amount for adults: Orally, starting at 2.5mg / time, twice a day, and then doubling the dose every 3 days, gradually increasing the effect, maintaining the amount of 10-40 mg daily, single or divided. Do not exceed 100 mg per day.

2. Commonly used amount in children: oral dose of 0.2mg / kg daily, once a day. After that, the dose will be adjusted every 3 days, and the daily weight increase will be 0.1mg / kg every day, and the maximum amount will be 50mg per day under 12 years old. The maintenance amount is 0.25 1mg / kg per day, and it is taken daily or in divided doses.

Minoxidil adverse reactions

Common are:

1. Reflexive sympathetic excitement can cause increased heart rate, arrhythmia, and flushing of the skin;

2. Water and sodium retention cause weight gain and lower limb edema.

3 Hair hyperplasia occurs on the face, arms, and back. It usually appears within 3 to 6 weeks after treatment and subsides after 1 to 6 months after treatment. To reduce these adverse reactions, it should be combined with diuretics or -blockers.

Rarely: angina, chest pain (pericarditis), headache (caused by vasodilation).

Rarely: allergic reactions, rashes, itching.

Minoxidil precautions

1. After using this product, blood urea nitrogen and creatinine increased in the early stage, but decreased to the pre-dose level after continuing treatment.

2. Plasma renin activity, serum alkaline phosphatase, and blood sodium may increase.

3 Blood cell counts and hemoglobin may decrease due to blood dilution.

4 Blood pressure and weight should be measured regularly when applying this product.

5. Sudden discontinuation of medication can cause blood pressure to rebound, so it should be withdrawn gradually.

Minoxidil medication for pregnant and lactating women:

This product can pass through the placenta, human studies are not sufficient, and it has a lethal effect in rats and rabbits. Therefore, pregnant women should be used with caution. Can be excreted into milk, but no effects on infants have been reported. No data are available on lactating women.

Minoxidil for children:

Lack of research on pediatric safety.

Minoxidil for elderly:

The elderly are sensitive to the antihypertensive effect, and the renal function is often poor. The dosage of this product must be reduced.

Minoxidil Drug Interactions:

1. This product can be used with other antihypertensive drugs and nitrates to increase the antihypertensive effect.

2. Nonsteroidal anti-inflammatory analgesics and sympathomimetic amines are used together with this product to reduce the antihypertensive effect.

Minoxidil overdose:

1. If the heart rate increases due to reflex sympathetic excitement, a -blocker can be added.

2. If there is weight gain due to water and sodium retention, lower extremity edema, diuretics can be given to relieve them, and furosemide and other diuretics are often used.

3 Patients with pericardial effusion should stop taking the drug.

4 When this product is used in excess, it can be appropriately expanded and treated, and phenylephrine or dopamine can be given in critical conditions, but it is not advisable to use epinephrine or norepinephrine to avoid overexciting the heart.

Minoxidil Minoxidil Poisoning

Minoxidil works to dilate small arteries and lower blood pressure, and is used to treat refractory hypertension, severe hypertension and renal hypertension. Antihypertensive effect is fast, long-lasting effect, one-time medication can maintain the effect for more than 2 to 4 hours. Oral 5mg / d, divided into 1 or 2 doses, with an increase of 5-10mg every 3 days as a step increase dose, can be increased to 10-20mg / d, divided into 1 or 2 doses. Intravenous injection of LD50 in mice was 1 mg / kg.

Clinical manifestations of minoxidil

Adverse reaction

(1) Peripheral edema and tachycardia; temporary increase in hemoglobin and hematocrit.

(2) hirsutism is obvious on the face, neck, upper limbs and legs.

2. Poisoning performance

(1) Occasionally left heart failure can induce or exacerbate chronic congestive heart failure, pulmonary heart disease, induced angina pectoris, and persistent angina pectoris.

(2) Improper medication can cause hypotension, syncope, and cerebral blood supply disorders, and severe cases can cause cerebral infarction.

Minoxidil treatment

The main points of treatment for minoxidil poisoning are:

1. Immediately discontinue the medication. Those who take a large amount of oral medicine should induce vomiting, gastric lavage, and catharsis immediately.

2. Correct heart failure, give heart-strengthening agents, diuretics.

3. Control angina pectoris by giving nitroglycerin and so on.

4. Improve blood supply, give vasodilators, and treat ischemic syncope and cerebral infarction. ^[7]

Minoxidil mechanism

The effects of minoxidil are similar to those of hydralazine, but the effects are strong and durable. It directly acts on vascular smooth muscle, relaxes small arteries, reduces peripheral resistance, thereby reducing blood pressure, and has no significant effect on volume vessels. It can also reflexively excite the sympathetic nerves during hypotension to accelerate heart rate, increase cardiac output, increase plasma renin activity, and water and sodium retention. The increased heart rate is also related to the product's direct positive muscular effect on the heart. Its water and sodium retention is partly due to an increase in renin secretion, and partly due to an increase in the reabsorption of Na + and water by the renal tubules by directly acting on them. Water and sodium retention and increased cardiac output can reduce the antihypertensive effect of this product, so it is often not used alone but is used in combination with diuretics and beta blockers in patients with severe hypertension. Its mechanism of action may be due to metabolism in the body to minoxidil NO sulfate, which increases the permeability of vascular smooth muscle cell membranes to K +, promotes intracellular K + outflow, causes hyperpolarization of vascular smooth muscle cell membranes, and thereby relaxes vascular smooth muscle and Blood pressure drops.

1. The mechanism of hair growth caused by minoxidil is still not fully understood, and it is believed that there are multiple ways.

One theory is that minoxidil is metabolized into minoxidil sulphate in hair follicles and acts on K + channels to prevent free Ca2 + accumulation in the cytoplasm. This prevents epidermal growth factor from inhibiting hair production. As a result, hair growth is promoted.

Another possible reason is that minoxidil up-regulates the expression of vascular endothelial growth factor and its receptors. This response stimulates angiogenesis and hair growth. In contrast, phipot and his team recently discovered that minoxidil can regenerate hair in ischemic bald areas. Other researchers have shown that minoxidil is a potential prostaglandin epoxide synthase-1 Agonist. Minoxidil can increase the number of DNA-synthesizing cells. These changes lead to long-term hair extension and the conversion of vellus hair to permanent hair.

2. Minoxidil found in the treatment of hypertension that it can make hair (beards) longer and thicker. Therefore, it is currently being developed and applied as a medicine for treating male pattern baldness. It has been reported that it also has a certain effect on the treatment of alopecia areata. The exact mechanism by which it promotes hair growth is unclear. However, the vasodilator effect of the drug suggests that it may cause hair growth by enhancing blood supply. Minoxidil does have the effect of enhancing blood flow to the skin. However, we have not been able to accurately measure the blood flow in the hair follicles. It has also been reported that minoxidil directly affects the growth of keratinocytes. Minoxidil enhances the survival rate of keratinocytes in the culture medium and prolongs the lifespan of the cells. The same effect can be used to maintain the growth of hair cells. Cohen et al have also reported the effects of minoxidil on cultured keratinocytes. In the current study, we further developed the effects of minoxidil on cultured cells, and the effects indicate that the mechanism of action is different at different stages of cell growth. The most likely mechanism is that minoxidil affects calcium metabolism.

3. The question of how Minoxidil turned the hair follicles from the stationary phase to the growth and development phase has received widespread attention. It has been confirmed that some subjects who are highly hereditary with male baldness have their gonads removed before puberty, and baldness that cannot be expressed later unless the exogenous testosterone is provided. Once testosterone reaches the hair vesicles, hair growth stops, and even if the supply of exogenous testosterone is stopped, the vesicles cannot continue to grow.

Therefore, it is impossible to treat male baldness with androgens. Hormone hormones enter the cells and are fixed to cytoplasmic receptors. Once bound, they are transported to the nucleus. In the nucleus, they make DNA Reverse transcriptases, which are expressed in specific parts of the body and are controlled by RNA, produce proteins that cause changes in cellular metabolism. A drug that prevents the binding of hormone cytoplasmic receptors or DNA. This drug exhibits the activity of exogenous non-androgens, but drugs that rely on special proteins and convey hormone information should be selectively linked to DNA via hormones. A series of proteins can be produced. Minoxidil may have some of the characteristics of these proteins. If minoxidil occupies or binds to these proteins, its presence will hinder hormone-induced signals to the cells. This signal can stop hair growth, and as a result, hair grows as long as minoxidil is present, even without interference during the use of other androgen treatments. Personally, I think the best effect is that the produced protein has the best chemical binding properties with minoxidil. For those who have a lower affinity for minoxidil, the effect is poor. Those who do not respond have a different minoxidil reactant. Minoxidil helps us limit the expression of baldness genes.

Minoxidil effect and mechanism

(A) Stimulate the proliferation and differentiation of hair follicle epithelial cells: Normal human hair follicle epithelial cells are cultured in different concentrations of minoxidil. Minoxidil can stimulate the proliferation of hair follicle epithelial cells at micromolar concentrations. Minoxidil sulfate is an active metabolite that stimulates hair growth, while sulfate transferase activity is higher in the hair follicles than in the epidermis and dermis. In vitro histological culture of mouse tentacle hair follicles and experiments using 35s-labeled cysteine to synthesize hair keratin confirmed that both minoxidil and its sulfate have germinative effects. In vitro experiments show that the effect of minoxidil sulfate is 14 times that of minoxidil. If a human sulfotransferase inhibitor or sulfuric acid scavenger is added, it can inhibit the germinative effect of minoxidil, but it can affect the sulfate metabolites. Has no effect. Animal experiments show that minoxidil can increase the number of dermal papillae, hair matrix, outer hair root sheaths and the number of fibroblasts synthesized around the hair, thereby prolonging the hair growth period and promoting the transformation of a hair to terminal hair.

(II) Promote angiogenesis: increase local blood supply: hair growth relies on the vascular network of hair nipples to provide nutrition. During different hair growth cycles, the expression of vascular endothelial cell growth factor mRNA is different, and the growth factor of vascular endothelial cell growth factor mRNA in the dermis Papillary cells are strongly expressed, but less expressed during the degenerative and resting phases. Experiments show that minoxidil increases the expression of vascular endothelial cell growth factor mRNA and its protein in a dose-dependent manner, thereby promoting the formation of dermal papilla blood vessels and increasing local blood supply.

(III) Opening potassium channels: Opening potassium channels is an important step in regulating hair growth. Both in vivo and in vitro experiments in animal models have shown that minoxidil is a potassium channel activator, which increases the permeability of potassium ions and prevents calcium ions from flowing into people In the cell, as a result, the concentration of free calcium ions in the cell decreases, and in the presence of calcium ions, epidermal growth factor inhibits hair growth.

Clinical application of minoxidil

Androgenic alopecia

Saraswat: Treatment of male androgenetic alopecia with 2% minoxidil solution, 1 ml each time, 2 times a day, 1 in 3 patients with mild to moderate hair growth at 3 months, 12 months At that time, 56% of patients had a significant improvement in appearance. Double-blind, placebo-controlled, multicenter clinical trials compared 5%, 2%

The efficacy of minoxidil and placebo in the treatment of male androgenetic alopecia, 393 male patients were divided into 3 groups, and the drug was administered twice daily for 48 weeks. The results showed that 5% minoxidil promoted hair growth significantly better than 2% minoxidil and placebo. By 48 weeks, the hair growth was 45% more than the 2% minoxidil group, according to the hair count 5% Minoxidil is earlier than 2% in response to treatment. In addition, the questionnaire on the quality of life of patients shows that 5% minoxidil is more conducive to improving the patient's psychological feeling. [$ 70 Price [191 Of 2%, minoxidil, and placebo on hair weight and quantity in male androgenic alopecia patients, 4 groups of 9 patients, each receiving 5% minoxidil, 2% minoxidil, and placebo And no treatment, the first 3 groups were double-blinded studies. Results: After using the drug for% weeks, the increase in hair weight was 5% minoxidil> 2% minoxidil> placebo. The differences between the groups were significant, but there was no significant difference in the number of hairs. Stop treatment and observe 24 The weight and number of hairs of minoxidil treated patients fell to placebo levels, suggesting that minoxidil did not alter the genetic quality of patients with androgenetic alopecia. Although no statistical comparison was made, the placebo and untreated groups had similar effects. In a 5-year clinical trial, 31 male patients with androgenetic alopecia had 2% and 3% minoxidil in their nephew. After one year of treatment, hair regeneration peaked, and then the hair growth slowed down. At 5 years, there was still significantly more non-pilling hair than at the beginning of treatment.

Minoxidil is also effective for female androgenic alopecia. A double-blind, placebo-controlled, multi-center trial observed the efficacy of 2% minoxidil in treating androgenetic alopecia in women. 256 women received 32 weeks of treatment and objectively evaluated the regenerating non-piled hair using accurate imaging techniques. Quantity, _ In the 1 cm "evaluation area, the treatment group regenerated an average of 23 non-xin hairs compared with 11 in the placebo group, and observers thought that 13% of those receiving 2% minoxidil had moderate hair Regenerative, SO% had mild hair regeneration, significantly higher than the placebo group. Similarly, 60% of patients receiving 2% minoxidil reported new hair growth, which was also higher than the 2% observed in the placebo group. The effect of nodil on the amount of hair in female patients with androgenetic alopecia, 8 patients were randomly divided into two groups and received 2% minoxidil or placebo, respectively. At 32 weeks, the hair in the target area of lc expansion was collected and counted. Total weight and quantity, total hair weight in the minoxidil group increased by 45%, while in the placebo group increased by 1.9%, the average number of hairs increased by 29.9% and -2.6%, respectively. Topical topical minoxidil combined with finasteride Amines can improve the efficacy, finasteride is type I 5. One of the reductases A specific inhibitor that blocks the conversion of trefinone to dihydrotridone. In an open, randomized, parallel-controlled study, 100 male androgenetic alopecia patients were graded 2 to 5 in Hamilton and finasteride was administered orally daily 1 mg combined with topical 2% minoxidil for 1 year, 94.5% of cases had mild to moderate hair growth, and 5.56% of patients had dense hair growth, which was better than the topical minoxidil group alone or non-oral only In the androstamine group, it has also been shown in animal experiments that the combination of the two is more effective than the use alone.

Minoxidil treatment

Alopecia areata, alopecia areata is a common chronic inflammatory skin disease. A considerable proportion of patients have a tendency to heal themselves, but those with recurrence, long course or extensive hair loss have a poor prognosis. Many treatments can promote hair growth in alopecia areata, but it has not been proven which method can change the natural course of alopecia areata, and there are few randomized controlled clinical studies. Minoxidil has a certain effect in treating alopecia areata, and it appears to be dose-dependent. Fiedler-Weis. [B] Treated 47 patients with severe alopecia areata with 5% minoxidil solution, 20 males and 27 females. After 48 to 60 weeks, 40 (85%) had terminal hair growth, but most of them could not reach Cosmetic requirements, compared with previous studies with 1% minoxidil, the effect of 5% on hair regeneration is significantly better than 1% minoxidil. Fransway et al. Treated 21 patients, 13 females and 8 males. Except for 2 cases with hair loss of nearly 2/3 of the area, the rest were alopecia areata or general baldness. The average duration of disease was 11.5 years. The nephew was twice a day for 1 year, and only 12 cases had short sparse hairs.

Minoxidil chemotherapy

Hair loss caused: Many drugs affect the hair growth cycle and cause hair loss. Hair loss is a significant adverse effect of anti-tumor drugs. Minoxidil can reduce hair loss caused by chemotherapy. Duvi. Etc. ["] A randomized double-blind trial was performed on 22 women who received chemotherapy after surgery. The degree of hair loss and hair regeneration were better in 2% of patients treated with minoxidil than in the placebo group. However, previous studies have concluded that it cannot be prevented Hair loss caused by doxorubicin.

Minoxidil adverse reactions

The main adverse reaction of minoxidil solution is hirsutism. A large-scale safety trial showed that minoxidil is safe and effective in treating androgenic alopecia, without increasing cardiovascular events and without significant systemic adverse reactions. A placebo-controlled clinical trial involving 1,333 women with androgenetic alopecia: a spontaneous report combined with investigator inquiry to investigate hair growth in areas other than the scalp. Hirsutism occurred in 4% of cases and was dose-related (5% minoxidil> 2% minoxidil>; placebo), 9 cases (7 cases 5% minoxidil, 2 cases 2% m (Noldil) discontinued due to hairiness. Five cases of androgenetic alopecia were treated with 5% minoxidil for 2 to 3 months, and severe hirsutism on the face and limbs occurred, but the hair on the face and upper limbs disappeared from 1 to 3 months after drug withdrawal, 4- -5 months of hair loss in the lower extremities, hirsutism may be related to the systemic absorption of minoxidil and the hair follicles in these areas are highly sensitive to minoxidil. The US FDA has approved 2% and 5% minoxidil solutions as over-the-counter drugs, the former is applicable to both men and women, and the latter is only applicable to men. Minoxidil solution can cause irritating or allergic contact allergic reactions. Some patients may Symptoms of rash and dandruff appear, but patch tests on patients with allergic contact dermatitis show that for most patients, the propylene glycol solvent is the real allergen, not minoxidil itself. Therefore changing the solvent can avoid some allergic reactions. 5% minoxidil is more likely to cause local irritation than 2% minoxidil. It is reported that topical application of 5% minoxidil can cause contact pigmented dermatitis.

Minoxidil Possible Mechanism

The mechanism of Minoxidil for hair loss is unknown. Current research suggests that Minoxidil can directly stimulate the proliferation and differentiation of hair follicle epithelial cells; promote blood vessel formation and increase local blood flow; open potassium ion channels; and make hair follicles from the resting phase to the growing phase Conversion. Minimal absorption by topical minoxidil system. There are sufficient clinical trials to confirm that minoxidil has a good effect on androgenetic alopecia and alopecia areata, but long-term medication is needed to maintain the effect. The shorter the time of hair loss, the smaller the area and the better the prognosis. High concentration is better than low concentration, but it also causes more local adverse reactions. Large-scale clinical trials have proven that topical minoxidil is feasible for the treatment of hair loss.

Minoxidil for hair loss

Androgen-induced hair loss

That is seborrheic hair loss. Minoxidil solution for male androgenetic alopecia, 1 ml each time, 2 times a day, 2/3 of patients with mild to moderate hair growth at 3 months, 74% of patients at 12 months The appearance is significantly improved. Minoxidil is also effective for female androgenic alopecia.

Minoxidil chemotherapy for hair loss

Many drugs affect the hair growth cycle and cause hair loss. Hair loss is a significant adverse effect of anti-tumor drugs. Minoxidil can reduce hair loss caused by chemotherapy.

Minoxidil alopecia areata

Alopecia areata is a common chronic inflammatory skin disease. A considerable proportion of patients have a tendency to heal themselves, but those with recurrence, long course or extensive hair loss have a poor prognosis. Many treatments can promote hair growth in alopecia areata, but it has not yet been proven which method can change the natural course of alopecia areata, and there are few randomized controlled clinical studies. Minoxidil has a certain effect in treating alopecia areata, and it appears to be dose-dependent.

Mechanism of topical treatment of hair loss

Minoxidil is a vasodilator for the treatment of hypertension, but its mechanism for treating hair loss is not primarily a function of dilating blood vessels. According to experimental studies, in vitro culture of hair follicles, the addition of minoxidil can increase the growth time of cultured hair follicles. Hair follicle hepatocyte growth factor and vascular endothelial cell growth factor are the two main growth factors of hair papillae and have important regulatory effects on the hair growth cycle. Lachger et al. Reported that minoxidil can up-regulate the expression of vascular endothelial cell growth factor mRNA in hair papilla cells. Therefore, it is believed that minoxidil stimulates and maintains the growth of hair follicles and prolongs the growth period of hair follicles through the above cytokines, which increases the development of miniaturized hair follicles and promotes the formation and function of hair papilla blood vessels, thereby playing an important role in treating hair loss.

Topical treatment of androgenetic alopecia

Androgenic alopecia is also known as "seborrheic alopecia", "male hair loss" or "early baldness". It can occur in both men and women. But their clinical manifestations are different. Male androgenetic alopecia begins with the horns on both sides of the forehead, gradually decreases in an M shape, and ends with most or all of them. There are also cases where the forehead, the horns, and the top fall off at the same time, or from the top, but the hair on the pillow is generally not affected. Androgenetic hair loss in women is mostly thinning hair on the top, while the forehead remains unchanged. Both males and females are mostly 12-40 years old and belong to polygene inheritance. In addition to genetic factors, the pathogenesis of this disease is closely related to androgen metabolism.

Minoxidil topical for androgen-induced hair loss in men

In 1988, the US FDA approved 2% minoxidil solution for external use to treat male androgenetic alopecia. There were 2294 male patients aged 18 to 50 years with mild to moderate top hair loss. After 12 months of treatment, the amount of hair grown in the minoxidil group increased. Later, Trancik et al. Applied 5% minoxidil and placebo in 393 male androgenetic alopecia, and after 48 months of treatment, the hair count in the 5% minoxidil group was 2% minoxidil This group was 45% higher and 5 times higher than the placebo group. In 1997, the FDA approved a 5% minoxidil solution for male pattern hair loss. Price and other 5% minoxidil for external use are more effective in promoting hair growth and increasing hair than in the placebo group and the non-treatment group. The efficacy mostly occurred 2-3 months after treatment, but was stopped at 96 weeks and followed for 4 weeks Hair loss began to appear again. This result also shows that minoxidil topical treatment can promote hair growth. The use of minoxidil for topical treatment of hair loss is: about 1 mL of topical application 2 times a day. Apply directly to the scalp and spread with your fingers. Because the effect often appears after 2 months of application, it should be explained to the patient at the beginning of treatment that the medication should be adhered to, and the treatment should be maintained after the effect appears.

The side effects of minoxidil for external use are mainly irritating reactions, that is, dryness, desquamation, itching, and redness in the application site. The incidence of 5% solution is 20%. These side reactions occur with the concentration of propylene glycol. There have also been reports of allergic contact dermatitis or photoallergic contact dermatitis. Another skin side effect is hypertrichosis, which occurs less frequently in men. 5% minoxidil solution, applied 1 mL twice a day, does not cause changes in blood pressure, pulse or weight. Because according to the study of pharmacokinetics, using 5% minoxidil solution, the average value measured in serum is 1.2ng / mL, which is far lower than the minimum amount of 20.0ng / mL required to cause blood pressure and pulse hemodynamic changes. .

Minoxidil Classification

Minoxidil is classified by recipe

1 is minoxidil hair growth liquid with propylene glycol, 2 is minoxidil series solution without propylene glycol

1) Minoxidil Hair Growth Liquid with Propylene Glycol Minoxidil Hair Growth Liquid: The main ingredients contain alcohol, propylene glycol, purified water, and Minoxidil, the relevant brands of hair growth water in the United States and domestic ones are the same as those containing propylene glycol The formula is the first generation of Minoxidil formula invented in the United States in the 1990s. The most economical price is Koran Syrup, which costs about 40 yuan per bottle.

The domestically produced minoxidil solutions are mainly:

a) 5% concentration of minoxidil,

b) 5% concentration minoxidil.

The above are all first-generation minoxidil formulas, which contain propylene glycol and are susceptible to allergies, resulting in repeated effects.

2) propylene glycol-free minoxidil series

Because the early (first generation) minoxidil hair growth solvent contains a large amount of propylene glycol as a moisturizing ingredient. Propylene glycol is a common humectant, and its side effects are increased skin irritation, dermatitis, dandruff and hair loss.

In the overall use process, more than 20% of patients are allergic to propylene glycol, which results in increased dandruff, itchy skin, and increased greasy feeling, which can lead to a rapid increase in hair loss. According to statistics, the probability of allergy to propylene glycol during the use of Asian patients is higher than that of patients in Western countries, which is close to 30%. More importantly, the allergy to diols may occur at any time after taking the medicine, and it may be early. Occurs, or may occur suddenly after using for several months, thus causing unnecessary repeated hair loss. Glycerin-based "propylene glycol-free minoxidil" series of hair shampoos developed in the United States have avoided such side effects. Minoxidil without propylene glycol is divided into 3% propylene glycol-free minoxidil (for women), 5% propylene glycol-free minoxidil and 15% propylene glycol-free minoxidil hair shampoo, combined with ampoulesol Tong Hair Loss Emulsion is the mainstream method for treating male hormone-induced hair loss (ie, seborrheic alopecia) in western countries.

Minoxidil classified by concentration

Minoxidil can also be classified according to concentration and targeted at different groups: 2% (including propylene glycol) or 3% (excluding propylene glycol). Minoxidil is for women only, 5% minoxidil is unisex, 15% Minoxidil is for men.

Minoxidil solution use

3% how to use minoxidil

The 3% minoxidil solution is specially formulated for women and does not contain propylene glycol, making it less susceptible to allergies. Female patients use 3% of minoxidil once a day in the morning and evening. The interval between two times is more than 8 hours. It can be applied with a nozzle, a dropper or a cotton swab. However, the size of the hair loss area varies from person to person, so you can increase or decrease the amount as needed depending on the actual situation. In the case of female patients using amphetamine lotion in combination with treatment, please use amphetamine in the evening 1 hour after using minoxidil.

How to use 5% Minoxidil

This product should be used when the hair and scalp are completely dry; once a day, morning and evening, 1 ml each time, the interval between the two times is more than 8 hours, you can use the attached nozzle or dropper;

After applying the medicine, you can spread it evenly with your fingers to ensure that all the hair loss areas are used, but you don't need to massage the scalp intentionally, and the massage will not improve the effect.

If it is combined with ampoulesone anti-hair loss lotion to improve the effect, please use ampoulesone 1 hour after minoxidil. If the interval is too short, minoxidil may react with ampoulesone components and cause effects Drug absorption and efficacy.

15% how to use minoxidil

Use once a day, averaging 1 ml each time, and apply to the scalp in the area of hair loss. Can be used in the morning or at night.

If it is combined with amphetamine anti-hair loss lotion to improve the effect, please use amphetamine 1 hour after 15% minoxidil. If the interval is too short, minoxidil may react with amphetamine ingredients, Lead to affect the absorption and efficacy of the drug. You can also use 15% of minoxidil in the morning and amphetamine lotion in the evening.

Minoxidil benefits

1) Compared with ordinary minoxidil solutions (such as Loki, Mandi, and Koran), propylene glycol-free minoxidil does not cause any allergies (such as scalp inflammation, swelling, scaling, folliculitis, oily Too much, extreme itching of the scalp, hair loss and so on).

2) Compared to ordinary minoxidil solution, it dries faster. Ordinary minoxidil contains propylene glycol, which can cause hair to become oily all day long. It can be seen that minoxidil, which has been used in medicine, does not contain propylene glycol , Generally absorbed within 60 minutes and approximately dried.

3) Glycerin is used instead of propylene glycol for minoxidil solution without propylene glycol. Glycerin is an essential ingredient in most skin care products, so it has a moisturizing and protective effect on the scalp.

4) Mino without propylene glycol does not have any peculiar smell, so there will be no questioning dilemma.

5) The effect of minodiol without propylene glycol is exactly the same as that of ordinary minoxidil solution.

101 Minoxidil Chapter Light 101 Event

On August 3, 2010, two products of Zhang Guang 101, claiming 100% Chinese herbal medicine care, were found to contain the ingredient "Minoxidil" in Singapore and Hong Kong, and were ordered to be recalled and removed from the shelves. Zhangguang 101 Group issued a statement on August 4 stating that the product in question was not sold in the Mainland and stated that Zhangguang 101 had formulated the formula according to the principles of traditional Chinese medicine and that the formula did not contain minoxidil. After the company's preliminary inspection, the export product produced by the Zhejiang factory contained a trace amount of minoxidil. Because of the overall relocation of the Zhejiang factory, the alcoholic solution containing the minoxidil positive reference substance was used as the raw material alcohol accidentally flowing into the export product Due to the extraction workshop, the company did not intentionally add it.

In response to this incident, the Zhejiang Food and Drug Administration has filed an investigation into the production plant in Zhejiang. The relevant person in charge of the Zhejiang Drug Administration stated that on September 13, Zhang Guang 101 was investigated in Singapore for containing western medicine ingredients Minoxidil. The Zhejiang production plant involved was formally put on record, and the products are currently being tested, with results soon. The State Food and Drug Administration notified on September 20 that the Zhejiang Food and Drug Administration had been instructed to supervise and inspect Zhejiang Zhangguang 101 Co., Ltd. according to law. After preliminary investigation, some products exported by Zhejiang Zhangguang 101 Co., Ltd. to Singapore and Hong Kong contained the banned component minoxidil. The investigation revealed that the company also had problems such as incomplete production process records, irregular inspections and retention of samples. Zhejiang Food and Drug Administration has issued a Notice of Order Correction in accordance with the law, requiring the company to rectify immediately, and at the same time to conduct in-depth investigations into the reasons why the related products contain the minoxidil component.