AIMTo increase the solubility and bioavailability of all-trans retinoic acid (ATRA).

METHODSUsing the principle of lecthin/bile salt mixed micelle to prepared ATRA injection. The best formulation was obtained by the turbidity and three-phase figure.

RESULTSATRA mixed micelles injection is stable. The average size of the mixed micelle is 17.8 nm, poly. index 0.495, zeta potential -16.5 mV.

CONCLUSIONThe method can be used to prepare the stable injection.

Antineoplastic Agents ; administration & dosage ; chemistry ; Bile Acids and Salts ; Drug Stability ; Micelles ; Phosphatidylcholines ; Solubility ; Technology, Pharmaceutical ; methods ; Tretinoin ; administration & dosage ; chemistry

Although many regimens for the acne therapy were proposed and vere used upto date, there is, no ideal choice of treatment. Since a certain relationship between the vitamin A and some dermatoses accompanied, with dyskeratoses had been proposed by Harris in 1932. many studies have been reported for the acne treatment with vitamin A topical or oral administration. (Straumfjord 1943, Lynch & Cook 1947, Anderson & Stokoe 1968). In 1969, Kligman observed the peeling effect of vitamin A acid (VAA), a metabolite of vitamin A, on the human skin and he experienced very good effect of VAA topical application on acne patients. Tbereafter, many authors studied about the VAA and reported the excellent effect on acne (McGills et al. 197l, Mills R Plewig 1972, Juhlin 1975). Moxeover, in 1976, Kim & Lee observed similar results with the authors mentioned above in its cure rate and side effects. In contrast to their high cure rate in those studies, however, its untoward side effects were freqvently elicited with severe intensity. So, author studied the effectiveness and side effects of VAAD which was changed in its chemical structure to diminish the side effects of VAA. Thirty-seven patients (M:F=4:33) were studied, and the results obtained were as follows. 1. The total number of lesions decreased significantly from third week and decreased by half in 4th. week. 2. The number of closed comedones decreased significantly from second week but the number of open comedones temporarily increased in 1st. week and decreased thereafter. 3. pustules and papul s continually decreased but new pustule formation developed in 3 patients and also disappeared in 4 weeks of treatment. 4. Allergic contact dermatitis was developed in 1 patient among 37 patients in 4th. week. 5. There were some undesirable side effects of scaling, pruritus, buming sensation in about 80% respectively, but its intensity was mild or moderate, and fissure, edema and exudation which appeared in VAA treatment were not observed. only a few patients complained tightness, erythema and pain. In comparison with VAA, the duration of treatment with VAAD was delayed about 1-2 weeks and the effectiveness in acne therapy with VAAD was almost equal to VAA therapy, and the side effects were markedly diminished.
Acne Vulgaris* ; Administration, Oral ; Dermatitis, Allergic Contact ; Edema ; Erythema ; Humans ; Pruritus ; Sensation ; Skin ; Skin Diseases ; Tretinoin* ; Vitamin A* ; Vitamins*

INTRODUCTION: Lamellar ichthyosis is a rare autosomal recessive disorder apparent at birth. Although not life threatening, it is disfiguring and causes considerable psychological stress.
CASE: We report a case of 15-year-old male with generalized, thick, dry, plate-like scales associated with ectropion and eclabium. At birth, he was enclosed in a transparent membrane that spontaneously shed revealing generalized pinkish skin. Non-pruritic plaques developed that evolved into plate-like scales. There was accompanying heat intolerance and tearing of eyes. Two siblings were similarly affected. Histopathologic findings were consistent with lamellar ichthyosis. The patient was treated with retinoic acid lotion and petroleum jelly. After three weeks, 50 percent improvement was noted with decrease in number and thickness of lesions.
CONCLUSION: This lifetime cutaneous disease affects the physical, mental and emotional state ofthe patient. It has no cure and treatment is directed symptomatically. We plan to continue topical treatment in this patient until significant improvement is attained.

Human ; Male ; Adolescent ; Administration, Topical ; Ectropion ; Emotions ; Eye ; Hot Temperature ; Ichthyosis, Lamellar ; Petrolatum ; Physical Examination ; Stress, Psychological ; Tretinoin

AIMTo evaluate the self-emulsifying ability and dissolution behavior of tretinoin in vitro and the pharmacokinetic behavior in beagle dogs.

METHODSThe self-emulsifying rate was evaluated by determining the intensity of scattered light at different time and the particle size of resultant emulsions after self-emulsifying were observed by optical microscope. The plasma concentrations were determined by HPLC and dissolution and pharmacokinetic behavior of self-emulsifying formulations were evaluated by comparison with commercial capsules.

RESULTSThe area under the curve (AUC) was significantly higher in the tretinoin self-emulsifying formulation group (3048.0 mg x h x L(-1)) than that in the commercial capsule group (1826.0 mg x h x L(-1)). Also, Tmax was smaller in the self-emulsifying formulation group (1.25 h) compared with market products (2 h) and the dissolved amount from self-emulsifying formulations in water at 15 min was much higher (more than 80%) than that of the market products (less than 5%).

CONCLUSIONThe self-emulsifying drug delivery systems can increase drug dissolution in vitro and absorption in vivo significantly.

Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Dogs ; Drug Delivery Systems ; Emulsifying Agents ; Emulsions ; Male ; Particle Size ; Polysorbates ; Solubility ; Tretinoin ; administration & dosage ; pharmacokinetics

OBJECTIVETo evaluate the effectiveness of AML-XH-99-M3 protocol for treatment of acute promyelocytic leukemia (APL) in children.

METHODSThirty-three children with APL received AML-XH-99-M3 protocol treatment. The event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) were evaluated by the Kaplan-Meier medthod with SPSS13.0 software.

RESULTSThirty patients (90.9%) achieved a complete remission (CR) after one course of treatment. The total CR rate was 100%. Six patients (18.2%) relapsed in an average of 29.17 months (16-38 months). Two patients (6.1%) died. The 7-year EFS and DFS in the 30 patients were 73.4+/-9.4%. The overall survival rate was 91.2+/-6.0%. The difference of EFS was observed in patients receiving intermittent all-trans-retinoic acid (ATRA) administration or not in the maintenance therapy (88.9+/-10.5% vs 62.5+/-13.6%) (P<0.05).

CONCLUSIONSThe AML-XH-99-M3 protocol for the treatment of APL produced a higher CR rate and higher EFS, DFS and OS rates in children. Intermittent administration of ATRA in the maintenance therapy can improve EFS rate.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Cytarabine ; administration & dosage ; Daunorubicin ; administration & dosage ; Etoposide ; administration & dosage ; Female ; Humans ; Infant ; Leukemia, Promyelocytic, Acute ; drug therapy ; mortality ; Male ; Tretinoin ; administration & dosage

OBJECTIVETo explore the significance of combined therapy of arsenic trioxide (As2O3) and all-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL).

METHODSRetrospective study of 80 APL patients was performed and the complete remission (CR), the recovery time of peripheral hemoglobin and platelet, the early mortality, and the adverse reaction rates were analyzed between the ATRA group and the ATRA combined As2O3 group (combined group).

RESULTSCR rate of the combined group and the ATRA group was 91.7% and 87.5% respectively, which showed no significant difference; time of reaching CR, hemoglobin recovery, and platelet recovery for the combined group were 28.0 +/- 7.8 days, 22.36 +/- 8.72 days and 19.38 +/- 9.52 days respectively, while those were 47.7 +/- 10.9 days, 28.40 +/- 8.95 days and 28.03 +/- 7.29 days for the ATRA group, which suggested a significantly shorter period of the combined group of achieving recovery. With 7.1% compared to 13.2%, the early mortality of the combined group seemed lower than that of the ATRA group but with no significance observed (P>0.05). The adverse reaction rates of the two groups also lacked any significant difference (P>0.05).

CONCLUSIONCompared with using ATRA alone, the combined therapy of AS2O3 and ATRA was dominant in achieving CR and recovery for APL. Besides, the combined therapy carries the promise of reducing the early mortality with no aggravation of the adverse reaction.

Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Arsenicals ; administration & dosage ; Child ; Female ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Male ; Middle Aged ; Oxides ; administration & dosage ; Remission Induction ; Retrospective Studies ; Tretinoin ; administration & dosage ; Young Adult

Minoxidil induces hair growth in male pattern baldness and prolongs the anagen phase. All-trans retinoic acid (ATRA) has been reported to act synergistically with minoxidil in vivo: they can enhance more dense hair regrowth than either compound alone. We evaluated the effect of minoxidil combined with ATRA on hair growth in vitro. The effect of co-treatment of minoxidil and ATRA on hair growth was studied in hair follicle organ culture. In cultured human dermal papilla cells (DPCs) and normal human epidermal keratinocytes, the expressions of Erk, Akt, Bcl-2, Bax, P53 and P21 were evaluated by immunoblot analysis. Minoxidil plus ATRA additively promoted hair growth in vitro, compared with minoxidil alone. In addition, minoxidil plus ATRA elevated phosphorylated Erk, phosphorylated Akt and the ratio of Bcl-2/Bax, but decreased the expressions of P53 and P21 more effectively than by minoxidil alone. Our results suggest that minoxidil plus ATRA would additively enhance hair growth by mediating dual functions: 1) the prolongation of cell survival by activating the Erk and Akt signaling pathways, and 2) the prevention of apoptosis of DPCs and epithelial cells by increasing the ratio of Bcl-2/Bax and downregulating the expressions of P53 and P21.
Tretinoin/*administration & dosage ; Minoxidil/*administration & dosage ; Keratolytic Agents/administration & dosage ; Humans ; Hair/cytology/*drug effects/*growth & development ; Drug Combinations ; Dose-Response Relationship, Drug ; Cells, Cultured ; Cell Proliferation/drug effects

OBJECTIVETo retrospectively analyze the treatment outcomes and side effects of childhood acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) or ATRA + arsenic trioxide (As2O3).

METHODSFrom 1992 to 2006, 45 patients with newly diagnosed APL were enrolled. All of them were PML-RAR alpha positive. 24 patients were induced with ATRA (group A) and 21 with ATRA + As2O3 (group B). The remission rate and side effects were observed.

RESULTS1) 19 (79.2%) patients in group A achieved CR, while 21(100%) patients in group B achieved CR. The CR rate in group A was lower than that in group B (P=0.027). 2) The recovery time of coagulation parameters and PLT count in group B was shorter than that in group A. 3) The overall survival (OS) and event-free survival(EFS) in group A were 77.8% and 66.9% at 41 months of follow-up, and in group B were 100% and 100% respectively at 34 months of followup. Group A had a significant lower EFS (P=0.0357)than group B. 4) The time of PML-RAR alpha fusion gene converting to negative in group A was longer (P=0.026) than that in group B.

CONCLUSIONSATRA + As2O3 for patients with newly diagnosed childhood APL is a feasible treatment with higher CR rate, less side effects and longer long-term survival.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Arsenicals ; administration & dosage ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; genetics ; Male ; Oncogene Proteins, Fusion ; genetics ; Oxides ; administration & dosage ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Tretinoin ; administration & dosage

A highly sensitive, rapid and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitative determination of retinamido-ester in rat plasma was developed and validated. A simplified protein precipitation with acetonitrile was employed for the sample preparation. The separation was carried out on an Agilent TC C18 column (150 mm x 4.6 mm ID, 5 microm particle size) with the mobile phase consisted of methanol-water-formic acid (93: 7: 0.1). Simvastatin was used as internal standard. The detection was performed on a trap-quadrupole tandem mass spectrometer by selected reaction monitoring (SRM) scan mode via atmospheric pressure chemical ionization (APCI). The range of calibration curve was 0.05-50 ng x mL(-1) and the limit of quantification was 10 pg x mL(-1). The intra- and inter-day precision values were between 95.97% and 104.43%, and RSD was between 4.63% and 10.69%, respectively. This method was applied to determine the pharmacokinetic parameters. The main pharmacokinetic parameters of retinamido-ester after oral administration via gastric gavage of 2.5, 5, 10 mg x kg(-1) were as follows, T(1/2): (11.28 +/- 7.23), (8.90 +/- 3.82), (8.01 +/- 5.65) h; AUC(0-infinity): (103.41 +/- 61.46), (190.23 +/- 74.99), (421.66 +/- 229.20) ng x h x mL(-1); MRT: (6.31 +/- 0.75), (5.98 +/- 0.71), (6.18 +/- 0.97) h; CL/F: (30.10 +/- 13.67), (29.58 +/- 10.59), (31.18 +/- 17.51) L x h(-1) x kg(-1); Vd/F: (414.94 +/- 159.82), (356.16 +/- 139.85), (369.28 +/- 322.72) L x kg(-1), respectively.
Administration, Oral ; Animals ; Antineoplastic Agents ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Chromatography, Liquid ; methods ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; methods ; Tretinoin ; administration & dosage ; analogs & derivatives ; blood ; pharmacokinetics

Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Arsenicals ; administration & dosage ; therapeutic use ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Oxides ; administration & dosage ; therapeutic use ; Tretinoin ; administration & dosage