preface
azone is a new kind of high-efficient skin osmosis promoter. chemical and spectrum analysis results illustrated that the purity of the product made in our company is over 99% and its quality remains stable. its safety and function of prmoting percutaneaous absorption of active agents have been proved by pharmacological and toxicological experiments. generally with a few amount of azone medicines and nutritious cosmetics might increase their osmosis of active agents through skin doubly, therefore enhance their efficiency, decrease their dosage, and reduce the productive coast. due to its high efficient azone has been the first selected skin osmosis promoter in medicine, cosmetic, and animal medicine production in america, germany, and japan. newly applies of azone developed by our company in agrochemical, dyeing-printing, leather making productions would be further extended rapidly, which would bring a huge benefit to the mankind.
properties and characteristics
azone is a new kind of high-efficient nonpoisonous skin osmotic promoter. as its hypertonicity the product is able to effect the ordinary construction of corneal layer in living things’ surface, make the lipoids under skin to be fluid, promote active agent through skin to be absorbed.
azone appears colorless, odorless, transparent oil like liquid, stinkless and nonpoisonous. it does not dissolve in water, but can make an emulsion with water. it dissolves in most organic solvent such as alcohol, propanol, chloroform etc.. added in cold cream and friction compound the azone enable the products with a comfortable lubricity. the practices proved azone has some characteristics as follows:
1．high-efficient osmotic promotion:
azone has a high efficient osmosis even at the low concentration as 0.5-2.0%,which is more over that of the poisonous conventional promoter, dimythyl sulfoxide (dmso). the skin osmosis of azone at 1% concentration is 13 times greater than that of dmso at 50% concentration. similarly, 1.8% azone might enhance the osmosis of flurouracil (fu) over 80 times.
2．widely applicable:
azone has the osmosis promotion not only greatly on hydrophilic or hydrophobic medicines but also obviously on antibiotics, steroid hormones, and nucleosides. nowadays, azone has been widely used in nutritious cosmetics. as no irritation on skin and mucosa, azone might be applied directly on wounds.
3．minimum toxicity:
azone is safe in all most the medicine formulations. both ld50 of azone in abdominal and intravenous injection are 8g/kg. the conventional concentration used in other products of azone is at 1-10%. no harm and irritation have been observed when azone used in anti-inflammatory ointments at the concentrate 80%.
4．convenient for use:
the osmotic promotion of azone acts not noly when it is dissolved. in most cases, medicines might get a good osmosis when dropping azone into their solution and shake the solution to emulsion. azone might be used in any formulation according to the application purpose such as solutions, emotions, ointments, creams, suppository, films or plasters, which are applied on skin or mucomembrance include oral cavity, rectum and vagina.
5．help to reduce dosage of active agents:
the highest osmotic promotion of azone appears normally when the active agent at lowerconcentration. for example, 0.02% clindamycin with azone has a nearly same osmosis with 0.1 clindamycin without azone in the formulation. azone might deduce the active medicine in a large scale in its formulation, therefore, the advantage of azone’s osmotic promotion comes more obviouslywhen the active medicine is expensive or has side effects.
physical features and standard
the national pharmacy standard (1995) is adopted in azone production in the company. the technological items are as follows:
content: 97.0-102.0%
refractive index: 1.470-1.473 (25℃)
relative density: 0.906-0.926
bromide: 0.1%
heavy metal:0.001%
acidity and alkalinity: neutral reaction
the products have passed the examination of china medicine ＆ bioproduct examine institute.
1．acute oral toxicity test: ld50 was 7.3 ± 0.8g/kg, determined as nonpoisonous.
2．stimulation test: emulsions and creams with azone under 10% in content have no stimulation and anaphylactic reaction.
3．the chemical structure: determined by ir, nmr, and ms methods.
4．the purity: determined by gc was over 99% (average of 8 times).
the research on “pharmacological of azone and its effect on percutaneous absorption of muscone” proved that azone has a good osmosis through skin, minimum residue on skin and might be excreted rapidly. application muscone with azone might increase the concentration of the medicine in blood and organs, very helpful to deduce the dosage of the medicine.
clinic applications and effects of osmotic promotion
1．feifan weight reduce cream, a product of beijing feifan natural health-protection manufacture. amount of clinic applications proved the product has high efficient osmosis, obvious curative effect with azone and azone is helpful to reduce the active coast by decrease the active agents. this product has been examined by china medicine ＆ bioproduct examine institute. the examine result illustrated that the product with azone under 5% in its content has no irritation on skin, no anaphylactic reaction, and effective ratio achieved 100%. emulsion azone under 10% added in the cream the product has also no irritation and anaphylactic reaction on skin.
2．griseofulvinum, a well known as no effect antibiotic in extemal application, has been used successfully as active agent in “xuanjing”, a new effective anti-fungus medicine in skin disease treatment developed by shenyang medicine college with dmso and urea as compound osmotic promoter. instead the compound osmotic promoter with 1.5% azone the college developed a new ointment “xuanjing-a”, which had been proved enhanced osmosis of griseofulvinum through skin. extrinsic test results showed that the release ratio of griseofulvinum in the new product increased over 4 times in 4 hours, and the product had a release advantage follow the time went by. due to azone promote the osmosis and percutaneous absorption of griseofulvinum, “xuanjing-a” reduce its active medicine 75% less than in “xuanjing” and also reduce amount of dmso in it. azone not only make the product with no abnormal odor, appears fine and smooth, and remain stable, but also decrease the cream cost 0.8 yuan rmb per kilogram.
3．“yanxitong”, a welcomed ointment developed by shenyang medicine college, became a new product “yangxitong-a” using 1.2% azone as its osmotic promoter. animal tests proved that the new product has the anti-inflammatory and detumescence function 3-5 times more than the original ointment.
4．p-aminobenzoic acid (paba) is a conventional ingredient in anti-tanning products. test result of applying the solution of 5% paba with 3% azone and 5% paba solution only (ck) on naked mouse skin was that more paba was observed in corneal layer of the mouse skin in the first trial. it suggest that the trial with azone might increase paba accumulating in corneal layer 2-3 times more than ck, and the accumulation becomes the maximum in 4 hours. azone could enhanced the percutaneous absorption of pada, increase its accumulation, reduce its degradation in corneal layer, and therefore enhance anti-tanning function of the product.
5．“youth film” is a new kind of colloidal solution with azone as its osmotic promoter for dealing with comedones. clinic observation result in 20 patients was that, 11 cured, 5 recovered, 4 not recovered. the effective ratio was 80%. the result of control trial (5% tetracyclini hydrochloridum ointment) without azone was that 4 cured, 5 recovered, 11 not recovered. its cure effective ratio was 45%. the results had a significant difference (p＜0.05). this test proved that azone had a function on promoting medicine to be absorbed. no poisonous reaction was observed in all treatments.
gaojintm new azone
new azone has the osmotic promotion 20% higher than azone. its purity is over 99.8%.
new azone with the properties of higher osmotic promotion and more safely (only half toxicity than old azone) might use in high quality cosmetic and top medicine production. as the medicine quality increase new azone will adopted rapidly to replace azone in the field of medicine production.
the hydrophilic new azone filled in the gaps of high efficient skin osmosis formulation. as azone dose not dissolve in water it is limited to be used in a large scale. water-soluble new azone in gaojin brand with a new structure keeps also high osmosis function of azone. the product appears as a colorless, and transparent liquid in room temperature. even its viscosity might increase accompany with temperature dropping down, its function would not change. the water soluble new azone is able mixed with water in any ratio to make stable emulsion. it is widely used in medicine external application with water solution and some cosmetics such as hair-dying ointment, shampoo, face beauty film etc. the dosage of new azone in the products is 1-5%.
acute oral toxicity test: ld50＞10g/kg, it was determined as nonpoisonous.
skin irritation test: no stimulation and no anaphylactic reaction on skin.
