How Effective Is Dexamethasone for Asthma?

Dexamethasone (DXMS) was first synthesized in 1957, and was listed in the World Health Organization's standard list of essential drugs. It is one of the essential drugs in the basic public health system.

Chinese name: dexamethasone

Chinese alias: (11, 16) -9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione; (11, 16) -9-Fluoro-11,17 , 21-trihydroxy-16-methylp; Flumetasone; 9-Fluoro-16A-methyl prednisone

English name: dexamethasone

English alias: Dexamethasone; Auxiron; Pregna-1,4-diene-3,20-dione, 9-fluoro-11,17,21-trihydroxy-16-methyl-, (11, 16)-; mk125; 9a-fluoro -16a-methylprednisolone

Molecular formula: C ₂₂ H ₂₉ FO ₅

Molecular weight: 392.46100

Exact mass: 392.20000

PSA: 94.83000

LogP: 1.89570

CAS number: 50-02-2

MDL number: MFCD00064136

EINECS number: 200-003-9

RTECS number: TU3980000

BRN number: 2066551

PubChem number: ^[1]

1. Properties: white powder

2. Melting point (): 255 ~ 264

3. Specific rotation (º, C = 1, DIOXANE): 75

4. Solubility: soluble in water, 10mg / 100mL, 25 ° C; ethanol, 1mg / mL. ^[1]

No

No

1. Molar refractive index: 100.23

2. Molar volume (cm3 / mol): 296.2

3. Isometric Zhang Rong (90.2K): 812.3

4. Surface tension (dyne / cm): 56.5

5. Polarizability (10-24cm3): 39.73 ^[1]

Symbol: GHS08

Signal Word: Danger

Hazard statement: H360D

Cautionary statements: P201; P280; P308 + P313

Customs code: 2937210000

Danger category code: R40

Safety instructions: S45

Dangerous goods sign: Xn

Manufacturing patents: US pat 3,007,923 (1961 to Lab.Franc. Chimiother.), Ger pat 1,113,690 (1961 to Merck & Co.), Brit Pat 869,511 (to Upjohn)

A new production process method of dexamethasone 21-hydroxy compound, using intermediate 21-acetate as a substrate, semi-dissolving the substrate with an appropriate amount of methanol containing 0 to 10% chloroform, and using a base as a catalyst A hydrolysis reaction is performed. After the reaction is completed, the reaction solution is neutralized with acetic acid, and the reaction solution is concentrated under reduced pressure to an appropriate volume, cooled, filtered, and the filter cake is washed with water and dried to obtain a 21-hydroxy compound. This process can shorten the production cycle, improve the quality and yield of 21-hydroxyl, and reduce the content of impurities in 21-hydroxyl.

In 1958, Arth and Oliveto respectively synthesized dexamethasone. In 1960, Merck & Co. produced dexamethasone sodium phosphate, and more than 12 dexamethasone derivatives were on the market.

The chemical structure of dexamethasone is the introduction of a fluorine atom at the 9 position of the B ring of the prednisone and a methyl group at the 16 position of the D ring; both 9 fluorine and 16 methyl groups significantly enhance their anti-inflammatory activity, while the 16 methyl group significantly Reduces side effects of sodium retention by dexamethasone. Dexamethasone and prednisolone have a clinical bioequivalent dose ratio of 0.75: 5 and a biological half-life of 36-54 hours. They are listed as long-acting glucocorticoids.

Dexamethasone, like other glucocorticoids, has pharmacological effects such as anti-inflammatory, anti-endotoxin, immune suppression, anti-shock, and stress response enhancement, so it is widely used in various departments to treat a variety of diseases, such as autoimmune diseases, allergies , Inflammation, asthma and dermatology, ophthalmology. Dexamethasone Sodium Phosphate Injection is an indispensable first-aid drug to rescue critically ill patients. In the past ten years, clinicians have used dexamethasone Sodium Phosphate to treat and prevent allergies caused by various Chinese and Western medicines and fever caused by viral influenza. As a result, the clinical use of dexamethasone has increased year by year, and China has become the world's largest market for dexamethasone.

Method name: Dexamethasone API-Dexamethasone-High Performance Liquid Chromatography

Scope of application: This method uses high performance liquid chromatography to determine the content of dexamethasone in dexamethasone bulk drugs.

This method is applicable to dexamethasone APIs.

Principle of the method: Dilute the test sample with methanol and dilute it with mobile phase, enter the HPLC for chromatographic separation, and use an ultraviolet absorption detector to detect the peak area of dexamethasone at a wavelength of 240nm and calculate its content.

Reagent: 1. Acetonitrile

2. Methanol

Equipment: 1. Instrument

1.1 High Performance Liquid Chromatograph

1.2 chromatographic column

Octadecylsilane-bonded silica gel is used as a filler. The number of theoretical plates calculated based on dexamethasone peak should not be less than 3000. 1.3 UV absorption detector

2. Chromatographic conditions

2.1 Mobile phase: acetonitrile water = 4 6

2.2 Detection wavelength: 240nm

2.3 Column temperature: room temperature

Sample preparation:

1. Preparation of reference solution

About 15 mg of dexamethasone reference was accurately weighed, placed in a 50 mL volumetric flask, 2 mL of methanol was added to dissolve it, diluted with mobile phase to the mark, and shaken to obtain the reference solution.

2. Preparation of test solution

Approximately 15 mg of the test sample is accurately weighed, placed in a 50 mL measuring bottle, 2 mL of methanol is added to dissolve it, and then diluted to the mark with mobile phase, and shaken to obtain the test solution.

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.

Operation steps: Precisely draw 10 mL of each of the reference solution and the test solution, and inject them into a high performance liquid chromatograph. Measure the peak area of dexamethasone (C ₂₂ H ₂₉ FO ₅ ) with a UV absorption detector at a wavelength of 240 nm. Show its content ^[2]

Source (name), content (potency)

This product is 16-methyl-11, 17, 21-trihydroxy-9-fluoroprogestin-1,4-diene-3,20-dione. Calculated based on dry products, C ₂₂ H ₂₉ FO ₅ should be 97.0% 102.0%.

Character

This product is white or off-white crystalline powder; odorless.

This product is slightly soluble in methanol, ethanol, acetone or dioxane, slightly soluble in chloroform, very slightly soluble in ether, and almost insoluble in water.

Specific rotation

Take this product, weigh it accurately, add dioxane to dissolve and quantitatively dilute it to make a solution containing about 10mg per 1ml, and measure it according to law (Appendix VIE of Pharmacopoeia Part II of 2010 Edition). The specific rotation is + 72 ° to +80 °.

Absorption coefficient

Take this product, weigh it accurately, add ethanol to dissolve and quantitatively dilute it to make a solution containing about 10 g per 1 ml, and measure the absorbance at 240nm according to the UV-visible spectrophotometry (Appendix IVA of Pharmacopoeia Part II of the 2010 edition). The absorption coefficient () is 380 to 410.

Identify

(1) Take about 2mg of this product, add 2ml of sulfuric acid, shake to dissolve, it will be reddish brown in 5 minutes, add 10ml of water to mix, and the color will disappear.

(2) In the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.

(3) The infrared absorption spectrum of this product should be the same as that of the control ("Infrared Spectra of Drugs" 741).

(4) The identification reaction of organic fluoride in this product (Appendix III of Part Two of the 2010 Pharmacopoeia).

an examination

relative substance

Take this product, accurately weigh, add methanol to dissolve and quantitatively dilute to make a solution containing about 0.5mg per 1ml as the test solution; take a betamethasone reference, accurately weigh, dissolve and quantitatively dilute with methanol Make a solution containing about 0.5mg per 1ml, accurately measure 1ml, place it in a 100ml measuring bottle, add 1ml of the test solution precisely, dilute to the mark with methanol, shake well, and use it as a control solution. According to the chromatographic conditions under the content determination item, take 20 l of the control solution and inject it into the liquid chromatograph, adjust the detection sensitivity, so that the peak height of the dexamethasone chromatographic peak is about 20% of the full scale. Then, 20 l of each of the test solution and the control solution was precisely measured and injected into the liquid chromatograph, and the chromatogram was recorded to 2.5 times the peak retention time of the main component. If a chromatographic peak corresponding to betamethasone in the reference solution appears in the chromatogram of the test solution, the peak area should be calculated according to the external standard method, and the content should not exceed 0.5%; the peak area of other single impurities should not be larger than the dexamethasone peak in the reference solution. Area (1.0%), the sum of the peak areas of each impurity must not be greater than 2 times (2.0%) the peak area of dexamethasone in the control solution. Any peak that is less than 0.01 times the area of the dexamethasone peak in the control solution chromatogram can be ignored.

Loss on drying

Take this product and dry it at 105 for 3 hours, and the weight loss shall not exceed 0.5% (Appendix L of Part Two of the Pharmacopoeia, 2010 Edition).

Residue on ignition

Must not exceed 0.2% (Appendix N of Part Two of the 2010 Pharmacopoeia).

Assay

It was determined by high performance liquid chromatography (Appendix VD of Part Two of the Pharmacopoeia, 2010 Edition).

Chromatographic conditions and system suitability tests

Octadecylsilane-bonded silica gel was used as the filler; acetonitrile-water (28:72) was used as the mobile phase; the detection wavelength was 240 nm. Take 20l of the reference solution under the relevant substance into the liquid chromatograph, record the chromatogram, the order of the peaks is betamethasone peak and dexamethasone peak, and the resolution should meet the requirements.

Assay

Take this product, weigh it accurately, add methanol to dissolve and quantitatively dilute it to make a solution containing about 50 g per 1 ml. Precisely measure 20 l into the liquid chromatograph and record the chromatogram; take another dexamethasone reference substance and measure it in the same way. . Calculate the peak area according to the external standard method.

category

Adrenal corticosteroids.

Store

Shaded and sealed.

preparation

Dexamethasone tablets ^[3]

Dexamethasone has a wide range of applications, strong effects and obvious curative effects. It is a commonly used glucocorticoid. It plays a key role in the rescue of allergic diseases, shock, endocrine crisis and other acute and critical diseases, and is an indispensable drug in clinical practice. Dexamethasone has stronger anti-inflammatory and skin allergy control effects than prednisone. Its 0.75 mg anti-inflammatory activity is equivalent to 5 mg of prednisone, which has a better effect on skin allergies. For critical conditions such as persistent asthma, large-scale intravenous infusion of dexamethasone has a good effect in the short term. It can be administered intravenously at a dose of 5-20 mg each time, and can be repeated for 4 to 6 hours. The dose can be reduced after 48 to 72 hours. 5 ~ 7 days discontinuation. For patients with cerebral edema caused by various reasons, 10 mg intravenous injection can be given for the first time. After that, intramuscular injection of 2 to 4 mg every 4 to 6 hours, usually remission within 24 hours, 48 to 72 hours reduction, drug withdrawal within 7 days.

Indications: Mainly applicable to allergic and autoimmune inflammatory diseases, such as connective tissue disease, severe bronchial asthma, dermatitis and other allergic diseases, ulcerative colitis, acute leukemia, and malignant lymphoma. This medicine is also used in the diagnosis of certain adrenal cortex diseases-dexamethasone inhibition test.

Dosage: Oral. The starting dose for adults is 0.75-3.00 mg (1-4 tablets) once, 2-4 times a day. The maintenance amount depends on the condition, about 0.75mg (1 tablet) per day.

Adverse reactions: A large dose of this product is likely to cause diabetes, osteoporosis, gastrointestinal ulcers and Cushing-like syndrome, and has a strong inhibitory effect on the hypothalamus-pituitary-adrenal axis. Complicated infection is the main adverse reaction.

Contraindications: Patients with a history of allergies to this product and adrenal corticosteroids are contraindicated

Precautions:

1. Hypertension, hyperthrombosis, gastroduodenal ulcer, psychosis, abnormal electrolyte metabolism, myocardial infarction, visceral surgery, glaucoma and other patients are generally not suitable for use. Weigh the pros and cons of use in special circumstances. However, attention should be paid to the possibility of worsening the condition.

2. It should be used with caution in patients with tuberculosis, acute bacterial or viral infections. If it is really necessary, it must be given appropriate anti-tuberculosis and anti-infective treatment.

3 After long-term medication, the dose should be gradually reduced before stopping.

4 Use with caution in patients with diabetes, osteoporosis, cirrhosis, renal insufficiency, and hypothyroidism.

Ingredients: [chemical name] The main ingredient of this product is dexamethasone.

Chemical name: 16a-methyl-11, 17a, 21-trihydroxy-9a-fluoroprogestin-1,4-diene-3,20-dione

Chemical Structure

[Molecular formula] C22H29FO5

[Molecular weight] 392.47

Properties: This product is a white tablet.

Medication for pregnant and lactating women:

1. Use by pregnant women can increase the incidence of placental insufficiency, neonatal weight loss or stillbirth, and teratogenic effects in animal tests. Pros and cons should be weighed.

2. Nursing mothers should stop breastfeeding when receiving large doses of drugs to prevent excretion of the drug through milk, causing adverse reactions such as infant growth inhibition and adrenal cortex function inhibition.

Medication for children:

If children use adrenocortical hormones, they must be very cautious, because hormones can inhibit the growth and development of children, if it is really necessary for long-term use, short-acting or intermediate-acting preparations should be avoided. Long-acting dexamethasone preparations should be avoided. And observe the changes in intracranial pressure.

Elderly medication:

Easy to produce hypertension; elderly patients, especially women after menopause, are prone to osteoporosis.

medicine interactions:

1. Taken with barbiturates, phenytoin, rifampicin, this product accelerates metabolism and weakens the effect.

2. Combined with salicylic acid drugs, it can reduce the salicylate blood concentration.

3 Can reduce the effect of anticoagulants, oral hypoglycemic agents, the dose should be adjusted.

4 Hypokalemia can be caused by combination with diuretics (except potassium-preserving diuretics). Pay attention to the dosage.

Pharmacological effects:

This product has more significant anti-inflammatory, anti-allergic and anti-shock effects than prednisone, and has a light effect on water and sodium retention and potassium excretion, and has a strong inhibitory effect on the thalamus-pituitary-adrenal axis.

1. Anti-inflammatory effect This product can reduce and prevent the tissue's response to inflammation, thereby reducing the manifestation of inflammation. Inhibits the accumulation of inflammatory cells, including macrophages and leukocytes at the site of inflammation, and inhibits phagocytosis, release of lysosomal enzymes, and synthesis and release of inflammatory chemical mediators. Can reduce and prevent the tissue's response to inflammation, thereby reducing the manifestation of inflammation.

2. Immunosuppressive effects include preventing or suppressing cell-mediated immune responses, delayed allergic reactions, reducing the number of T lymphocytes, monocytes, and eosinophils, and reducing the ability of immunoglobulins to bind to cell surface receptors, And inhibit the synthesis and release of interleukins, thereby reducing the transformation of T lymphocytes to lymphoblasts, and reducing the expansion of the primary immune response. Can reduce the immune complex through the basement membrane, and can reduce complement components and the concentration of immunoglobulin.

Overdose: Unclear.

Pharmacokinetics: This product is easily absorbed from the digestive tract. Its plasma half-life (T1 / 2) is 190 minutes, and the tissue half-life (T1 / 2) is 3 days. The plasma protein binding rate is lower than other corticosteroids.

Drug validity: 24 months

Implementation standard: "Chinese Pharmacopoeia" 2010 edition two

Warning / Warning words: shading, sealed (10-30 ° C) storage.

Manual revision date: 2007-01-13