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Objective@#To investigate the efficacy of antibacterial peptides in the adjuvant therapy of stage Ⅲ periodontitis.@*Methods@#Fifty-one patients were randomly divided into simple mechanical curettage group, minocycline hydrochloride group and antibacterial peptide group according to the treatment mode. Three groups received periodontal sequential treatment, and after the ultrasonic supragingival scaling, they were performed with curettage, root surface planing, polishing and flushing. After treatment in the minocycline hydrochloride group and the biological antibacterial peptide group, minocycline hydrochloride ointment and biological antibacterial peptide periodontal gel were injected into the periodontal pocket respectively. The mechanical curettage group did not take medicine. Periodontal checklists at baseline and 90 d after treatment were recorded to compare differences of the three groups in periodontal probing depth (PD), bleeding index (BI) and attachment level (AL). Enzyme-linked immunosorbent assay (ELSIA) was used to detect the change of tumour necrosis factor-α (TNF-α), interleukin (IL)-1β by collecting the gingival crevicular fluid of the three sets at baseline, 7 d after treatment and 90 d after treatment. @*Results@#There was no statistically significant difference in periodontal clinical examination indexes(PD,BI,AL) and contents of TNF-α and IL-1β in the gingival crevicular fluid between the three groups at baseline (P>0.05). At 7 and 90 d after treatment, all indexes in the three groups were improved compared with those before treatment. The comparison between groups showed that in periodontal pockets with PD≤5 mm, there was no statistically significant difference in the indicators between the three groups. In periodontal pockets with PD≥6 mm, the minocycline hydrochloride group and the bio-antibacterial peptide group had no statistically significant difference in various indicators, but they were all better than the mechanical scaling group.@*Conclusion@#Basic periodontal therapy is an important treatment for stage Ⅲ periodontitis. Minocycline hydrochloride and biological antibacterial peptides are both effective adjuvant drugs for deep periodontal pockets with PD≥6 mm.
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@#To prepare a minocycline hydrochloride microsphere depot and evaluate its release performance and physicochemical properties, poly (lactic-co-glycolic acid) (PLGA) was used as raw material, the minocycline hydrochloride microspheres were prepared by electrospray, and the morphology and size distribution of the microspheres were characterized by polarizing microscopy and scanning electron microscopy (SEM). The microspheres were then mixed with sucrose acetate isobutyrate (SAIB) depot at a ratio of 1:10 to form a minocycline hydrochloride microsphere depot, and its release performance and porosity changes were evaluated. The results showed that the microspheres had smooth surface and the diameter was (5.294 ± 1.222) μm. After the microspheres were added into SAIB depot, the burst release of minocycline hydrochloride significantly decreased from 60% to 3.27% at the first day, and then the release lasted for 42 days . Additionally, the porosity of the depot increased rapidly from (12.53 ± 0.43)% to (32.53 ± 0.43)% during days 0-15, and increased slowly from (32.53 ± 0.43)% to (33.81 ± 0.54)% during days 15-45. The minocycline hydrochloride microsphere depot prepared in this study is expected to be an effective way for the application of minocycline hydrochloride for its good release performance and simple preparation process.
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Objective To study the clinical efficacy of Nd∶YAP laser in the treatment of acute localized pericardial periodontitis. Methods A total of 120 patients with acute localized pericardial periodontitis were randomly divided into 3 groups, including Nd∶YAP laser group, minocycline group and control group (iodine glycerol group). All patients were underwent pretreatment of intracrevicular washing with 3.0％hydrogen peroxide and normal saline alternately. After the pretreatment, the patients in the Nd∶YAP laser group were given 3 min local Nb:YAP laser irradiation (1 time/d for 3 times), in the minocycline group were injected with minocycline hydrochloride ointment (1 time), and in the control group were treated with 2％iodine glycerol (1 time/d for 4 times) in gingival sulcus. One day after the treatment, the gingival index (GI), pain visual score (VAS), and opening degree of all patients were recorded, and the therapeutic effect was observed 5 days after the treatment. Results Compared with the minocycline group and the control group (iodine glycerol group), the GI value and VAS value of the Nd∶YAP laser group decreased and the openmouthed size increased (all P<0.05). At 5 days after the treatment, the patients in the Nd∶YAP laser group and the minocycline group had significant improvement in local gingival sulcusinflammation, and the total effective rate was 90％and 85％, which was significantly better than the control group (all P<0.05) and no significant difference in efficacy between the two groups (P>0.05). Conclusions The Nd∶YAP laser treatment inacute wisdom tooth pericoronitis can significantly reduce pain and improve openmouthed size, and has a good clinical efficacy.
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Objective To observe the curative effect of point tongue pill combined with minocycline hydrochloride ointment in the treatment of periodontal abscess .Methods From March 2017 to April 2018 ,70 cases of periodontal abscess in the Traditional Chinese Medicine Hospital of Chaoyang District of Beijing were selected and randomly divided into treatment group and control group ,with 35 cases in each group .Control group:local treatment of periodontal scaling ,curettage ,periodontal pockets at the bottom of minocycline hydrochloride ointment ,half an hour of fasting water,light diet.Treatment group:on the basis of the control group , the tongue point pills were given for 1 week.The curative effect was evaluated at the third ,seventh day after scaling and curettage .The diagnostic criteria of efficacy were PD,BOP,degree of pain and the size of abscesses .Results There were no statistically significant differences in the PD,BOP,pain and abscess size between the two groups before treatment (all P>0.05).At the third day after treatment,15 cases were healed (42.9％),12 cases were effective (34.3％) and 8 cases were ineffective(22.9％) in the treatment group.In the control group,12 cases were cured (34.3％),13 cases were effective (37.1％) and invalid in 10 cases(28.6％),and there was no statistically significant difference between the two groups (Z=0.757,P=0.449).At the seventh day after treatment ,26 cases were cured(74.3％),7 cases were effective (20.0％) and 2 cases were invalid (5.7％) in the treatment group,and 18 cases were cured (51.4％), 11 cases were effective (31.4％) and 6 cases were invalid (17.1％) in the control group.The difference was statistically significant (Z=2.058,P=0.040).Conclusion The curative effect of point tongue pill combined with minocycline hydrochloride ointment in the treatment of periodontal abscess is better than traditional western medicine .
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AIM:To investigate the effects of titanium dioxide(TiO2)nanotube arrays on the early adhesion behavior of Porphyromonas gingivalis(Pg),Tannerella forsythia(Tf)and Actinobacillus actinomycetemcomitans(Aa)be-fore and after loaded with minocycline hydrochloride(MN).METHODS: TiO2nanotube arrays were prepared by ano-dization and loaded with MN.Titanium slices were divided into 3 groups according to different treatment methods: pure polishing titanium(Ti)group,TiO2nanotube titanium(TiO2)group, and MN(120 μg)TiO2nanotube titanium(MN TiO2)group.The antibacterial properties of the titanium tablets were evaluated by the bacteriostasis test.RESULTS:The Ti had no antibacterial activity.The antibacterial activity of TiO 2to Aa,Pg and Tf was poor,with only about 20%of anti-bacterial rate after 4 h.After loaded with MN,its antibacterial activity was enhanced,and the antibacterial rate was up to 77%after 4 h.CONCLUSION: No antibacterial activity in the Ti group was observed.If TiO2nanotube arrays were formed on the surface and MN was loaded,the antibacterial activity on periodontal pathogens was stronger.
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<p><b>OBJECTIVE</b>This study aimed to evaluate the efficacy of 2% minocycline hydrochloride combined with flap surgery in the treatment of chronic periodontitis. The superiority of this therapy to simple flap surgery was also explored.</p><p><b>METHODS</b>We searched the databases of CNKI, VIP, Wanfang, Chinese Biomedical Literature, PubMed, ScienceDirect, and Embase from inception to July 2017. Two reviewers independently screened literature, extracted data, and evaluated the bias risk of included studies. Then, Meta-analysis was performed using RevMan 5.3 software.</p><p><b>RESULTS</b>A total of seven randomized controlled trials involving 217 patients were included. Meta-analysis showed that, in two groups, the changes in probing depth (PD) [MD=-0.55, 95%CI (-0.84, -0.26), P=0.000 2] and plaque index [MD=-0.08, 95%CI (-0.15, -0.01), P=0.03] at 3 and 6 months of PD [MD=-0.62, 95%CI (-1.04, -0.21), P=0.003] had statistically significant difference (P<0.05). The clinical attachment loss (CAL) [MD=-0.21, 95%CI (-0.47, 0.04), P=0.10] had no statistically significant difference after 3 months (P>0.05), but the improvement in CAL was significantly improved by minocycline hydrochloride combined with flap therapy.</p><p><b>CONCLUSIONS</b>Periodontal flap combined with minocycline adjuvant therapy for chronic periodontitis is effective in short-term observations.</p>
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Objective To explore the clinical effect of minocycline hydrochloride ointment and iodine glycerol in the treatment of chronic periodontitis and the effect on the inflammatory cytokines in gingival crevicular fluid (GCF).Methods A total of 90 patients with chronic periodontitis (115 affected teeth) in Stomatology Hospital of Zhangjiakou from December 2015 to December 2016 were included and randomly divided into observation group(57 affected teeth) and control group (58 effected teeth),with 45 patients in each group.All patients were given routine periodental non-surgical treatment,based on this,the patients in the control group were smeared iodine glycerol (20 g · L-1) in the periodontal pocket with a probe;the patients in the observation group were injected minocycline hydrochloride ointment in the periodontal pocket until the ointment overflowed the gingival margin.The patients in the two groups were treated one time a week for 4 weeks.After 4-week treatment,the gingival index (GI),gingival sulcus bleeding index (SBI),probing depth (PD),plaque index (PLI),periodontal attachment level (AL) and the clinical efficacy were recorded.The levels of hypersensitive C-reactive protein(hs-CRP),interleukin8 (IL-8),interleukin-10 (IL-10),tumor necrosis factor-α (TNF-α),matrix metalloproteinases-8 (MMP-8) and soluble intercellular adhesion molecule-1 (sICAM-1) were detected by enzyme linked immunosorbent assay before and after treatment and compared between the two groups.Results There was no statistic difference in GI,SBI,PD,PLI,and AL between the two groups before treatment (P ＞ 0.05);the GI,SBI,PD,PLI,and AL after treatment were significantly lower than those before treatment (P ＜ 0.05);the GI,SBI,PD,PLI and AL in observation group were significantly lower than those in the control group after treatment (P ＜ 0.05).There was no statistic difference in the levels of hs-CRP,IL-8,IL-10,TNF-α,MMP-8 and sICAM-1 in GCF between the two groups before treatment(P ＞ 0.05);the levels of hs-CRP,IL-8,TNF-α,MMP-8 and sICAM-1 in GCF after treatment were significantly lower than those before treatment (P ＜ 0.05),but the IL-10 level was significantly higher than that before treatment in the two groups(P ＜ 0.05);the levels of hs-CRP,IL-8,MMP-8,TNF-α and sICAM-1 in GCF in observation group were significantly lower than those in the control group after treatment (P ＜ 0.05);the level of IL-10 was significantly higher than that in the control group after treatment (P ＜ 0.05).The total effective rate of affected teeth in observation group(96.49％,55/57) was significantly higher than that in the control group (74.14％,43/58) (x2 =11.40,P ＜ 0.05).Conclusion Minocycline hydrochloride ointment can effectively improve the inflammatory reaction status in patients with chronic periodontitis,and it can control the inflammatory damage of periodontal tissues by inhibiting the inflammatory reaction,and effectively alleviate the clinical symptoms.
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Objective To investigate the effects of minocycline hydrochloride ointment on collagenase in gingival crevicular fluid.Methods 60 patients with chronic periodontitis treated in our hospital from January 2015 to December 2016 were selected as the research object, the patients were divided into two groups according to their intervention methods, 30 cases in each group.The control group was treated with ultrasound clean governance and iodine glycerol, the observation group was treated with ultrasound clean governance and minocycline hydrochloride ointment The experimental data of the two groups were compared.Results The index change of gingival crevicular fluid volume plaque index,,depth of exploration and clinical attachment loss in the observation group were better than those in the control group, the difference between the two groups was statistically significant (P<0.05);The clinical therapeutic effect of the observation group(93.3%)was better than that of the control group(73.3%), and the difference between the two groups was statistically significant (P<0.05).The incidence of adverse reactions in the observed group(10.0%)was lower than that in the control group(26.7%), and the difference between the two groups was statistically significant (P<0.05).Conclusion Minocycline hydrochloride ointment can affect the level of collagenase in gingival crevicular fluid, and the clinical effect of the treatment of chronic periodontal disease is significant.
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Objective To study the clinical effect of minocycline hydrochlorideointment on the treatment of patients with retrograde pulpitis.Methods From January 2015 to December 2016 in Huzhou central hospital, 90 cases with retrograde pulpitis as the research object were divided into two groups, the control group and the observation group, 45 cases in each group.The control group were received conventional treatment combined with iodine glycerin, and the observation group were given conventional treatment combined with minocycline hydrochloride ointment.The clinical data were compared in the two groups.Results After treatment, plaque index(0.91±0.30), gingival bleeding index(2.11±1.32), explore clinical depth(4.58±1.19)and attachment loss(3.06±1.85)in the observation group were better than the plaque index(1.38±0.49), gingival bleeding index(3.07±1.83),explore clinical depth(4.87±1.49)and attachment loss(5.18±1.39)in the control group, the difference between the two groups was statistically significant(P< 0.05);the clinical effect 95.6% in the observation group was better than 80.0% in the control group(P< 0.05).The adverse reaction rate was 6.7% in the observation group, which was lower than 17.8% in the control group(P< 0.05).Conclusion It that the conventional method combined with minocycline hydrochloride ointment on the treatment of retrograde pulpitis has significant clinical effect, can effectively improve the clinical symptoms of patients, is worthy of clinical application.
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Objective To investigate the safety and feasibility of Minocycline Hydrochloride Ointment and metronidazole membrane in the treatment of periodontal abscess.Methods80 cases of patients with periodontal abscess in our hospital from May 2014 to May 2016 were selected, these patients were randomly divided into Minocycline Hydrochloride Ointment group (n=40) and metronidazole membrane group (n=40) two groups, the periodontal probing depth, gingival bleeding index, plaque index, attachment loss, clinical efficacy, the incidences of adverse reactions and recurrence of the two groups were statistically analyzed.ResultsThe periodontal probing depth, gingival bleeding index, plaque index, attachment loss of the Minocycline Hydrochloride Ointment group were significantly lower (P<0.05), the total treatment efficiency 95% (38/40) was significantly higher than the metronidazole membrane group 77.5% (31/40) (P<0.05), the recurrence rate 2.5% (1/40) was significantly lower than the metronidazole membrane group 15% (6/40) (P<0.05), but the difference of the incidences of adverse reactions 10% (4/40), 7.5% (3/40) between the two groups was not significant.ConclusionMinocycline Hydrochloride Ointment metronidazole membrane in the treatment of periodontal abscess has higher safety and feasibility than metronidazole membrane, so is worthy of promotion in the clinical.
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Objective To investigate the clinical efficacy and mechanism of minocycline hydrochloride ointment adjuvant therapy for chronic periodontitis.Methods86 patients of chronic periodontitis who received therapy from August 2013 to June 2015 in our hospital were selected.According to random number table, those patients were divided into the experimental group (n=43) and the control group (n=43).The control group was treated on the basis of the foundation treatment with tinidazole Oral Sticking Tablets and the experimental group were treated on the base of the foundation treatment with Minocycline hydrochloride sustained-release ointment, the levels of hs-CRP, TNF-a, IL-8 and IL-10 in gingival sulcus fluid were measured before and after treatment, the indexes of PLI, PD, SBI and AL were recorded,at the same time the clinical curative effect between two groups was compared.ResultsThe effective rate of the experimental group(95.35%) was higher than the control group(81.40%),the difference was statistically significant (P<0.05);Compared with before treatment, two groups general situations and inflammation factors changed after treatment,plaque index, periodontal pocket probing depth, gingival sulcus bleeding index and adhesion levels of the experimental group were lower than the control group after treatment, the PD, SBI, AL and PLI in the experimental group were significantly lower than that of the control group, and the hs-CRP, TNF-a and IL-8 levels were lower than the control group, IL-10 was higher than the control group after treatment(P<0.05).ConclusionMinocycline hydrochloride ointment is well for chronic periodontitis,which can effectively relieve periodontal chronic inflammation, improve clinical efficacy, the underlying mechanism may be related to the reduction of IL-8 and TNF-α levels in gingival crevicular fluid.
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Objective To study the effect of minocycline hydrochloride ointment and ibuprofen on serum concentration of chronic periodontitis . Methods 86 patients with chronic periodontitis treated in our hospital from June 2014 to June 2016 were selected and randomly divided into two groups:observation group 43 cases, using minocycline hydrochloride ointment combined with ibuprofen treatment , the control group 43 cases, only the use of minocycline hydrochloride ointment for treatment.After treatment, the clinical efficacy of the two groups were observed, the level of plaque, the level of attachment, the level of gingival sulcus bleeding and the probing depth of periodontal pocket were recorded, the levels of IL-10, TNF-α, hs-CRP and IL-8 in serum and the incidence of adverse reactions were measured.Results The total effective rate was 90.7% in the observation group and 74.4%in the control group, which was significantly higher than that in the control group, the difference was statistically significant (P<0.05).The probing depth of the periodontal pocket, gingival sulcus bleeding index, attachment level and plaque index decreased to varying degrees in the two groups before and after treatment, the difference was statistically significant (P<0.05), patients in the observation group were significantly lower than those in the control group, the difference was statistically significant (P<0.05).After treatment, the levels of IL-8, hs-CRP and TNF-αin serum of the two groups decreased, IL-10 levels increased in different degrees, the difference was statistically significant (P<0.05).The observation group was better than the control group, the difference was statistically significant ( P<0.05 ) .Conclusion Minocycline hydrochloride ointment combined with ibuprofen has a good effect on patients with chronic periodontitis.It can effectively relieve the patient's condition and improve the serum concentration of patients.
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Objective To evaluate the effect of minocycline hydrochloride (MH)-loaded in-situ hydrogels on periodontitis of rats. Methods Ligation, high sugar diet, local vaccination of Porphyromonas gingivalis and intramusclar injection of acetic predniso-lone were combined to establish the periodontitis of rats. Whether periodontitis was established successfully or not was determined according to clinical examination and pathology after 4 weeks. 28 periodontitis rats were divided into the model group, the positive controll (MH ointment), the blank in-situ hydrogels (ISG) and MH-loaded ISG groups. The detection index included gingival index, bleeding index, bleeding on probing, and probing depth before treatment and 4 weeks after treatment, respectively. Results The inflame-matory and destruction degrees of periodontal tissues in the positive and MH ISG groups were better than those of the model and the blank groups. Conclusion The curative effect of MH-loaded ISG on periodontitis is obvious. It is expected to become a novel formulation to treat periodontitis in future.
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Objective To compare the clinical effect and safety of minocycline hydrochloride combined with metronidazole or tinidazole in treatment of chronic periodontitis.Methods Patients with chronic periodonitis (260 cases) accepted in Ninth Hospital of Xi'an from February 2014 to February 2016 were randomly divided into observation group and control group with 130 cases in each group.Patients in control group were given minocycline hydrochloride combined with metronidazole,and patients in observation group were given minocycline hydrochloride combined with tinidazole.Then the clinical effect,periodontal indexes and adverse reactions of two groups were compared.Results The total effective rate of observation group was 94.62％,which was obviously higher than that of control group (83.85％,P ＜ 0.05).The periodontal indexes of observation group were higher than control group (P ＜ 0.05).The adverse reaction rate of observation group was 8.46％,that of control group was 14.62％,which had no differences.The recurrence rate of observation group was 1.54％,that of control group was 6.92％,which had no differences.Conclusion Using minocycline hydrochloride combined with tinidazole has better effect in treatment of chronic periodontitis,which is safety and worthy of clinical application.
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Objective:To prepare minocycline hydrochloride sustained release tablets and optimize the formula .Methods: The method of dry granulation tabletting was used to prepare minocycline hydrochloride sustained release tablets .With the cumulative re-lease rate in 1, 2, 4 and 8 h as the index, the amount of HPMC E50 and HPMC K100LV was studied by central composite design re-sponse surface methodology .The in vitro release similarity of the sustained-release tablets and the reference tablets was compared .Re-sults:The optimized formula contained 35 mg HPMC E50 and 70 mg HPMC K100LV.The f2 for the sustained release tablets and the reference tablets in the different dissolution media was 79.06, 84.62, 75.46 and 72.95, respectively.Conclusion: Minocycline hydrochloride sustained release tablets with the formula optimized by central composite design response surface methodology meet the requirements.The results can provide evidence for the next industrial production .
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OBJECTIVE:To observe the efficacy and safety of minocycline hydrochloride combined with tinidazole in the treat-ment of chronic periodontitis. METHODS:100 patients with chronic periodontitis were randomly divided into observation group 1, observation group 2,observation group 3 and control group. Patients in control group were given full-mouth dental scalers and sub-gingival clean scraping,then 0.9% Sodium chloride injection and 3% hydrogen peroxide were used to alternately wash periodontal pocket bottom. Based on the treatment,observation group 1 was injected Minocycline hydrochloride ointment to periodontal pocket bottom until slight overflow after saliva isolation and desiccation,once a week;observation group 2 was given Tinidazole buccal tablet 1 tablet in the buccal middle gingival surface,twice a day,observation group 3 was given Minocycline hydrochloride oint-ment+Tinidazole buccal tablets(the usage and dosage was the same with above-mentioned 2 groups). The treatment course was 4 weeks. The clinical efficacy,PLI,PAL,PPD,MD,GI before and after treatment and incidence of adverse reactions were observed. RESULTS:The total effective rate in observation group 3>observation group 1 and observation group 2>control group(P0.05). After treatment, PLI,PAL,PPD,MD and GI in all groups were significantly lower than before,and observation group 30.05). There were no obvious adverse reactions during treatment. CONCLUSIONS:Minocycline hy-drochloride combined with tinidazole has better efficacy than minocycline hydrochloride or tinidazole in the treatment of chronic periodontitis,with good safety.
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Objective To observe the effect of minocycline hydrochloride sustained-release agent on interleukin-6 (IL-6) in gingival sulcus fluid of patients with chronic periodontitis.Methods One hundred and twenty patients with chronic periodontitis were randomly divided into two groups,the control group(n =60 cases) and the treatment group(n =60 cases).The patients in the control group were treated through oral tinidazole.The patients in the treatment group were given topical application of minocycline hydrochloride sustained-release agent.The plaque index,probing pocket depth,bleeding on probing rate and IL-6 in gingival sulcus fluid were detected before and after treatment.Results The plaque index,probing pocket depth,bleeding on probing rate were decreased after treatment.There was a significant difference between two groups(P ＜ 0.05).IL-6 level was decreased after treatment.There was a significant difference between two groups (P ＜ 0.05).Conclusion Minocycline hydrochloride can improve patients with chronic periodontitis through mitigating inflammation.
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Objective To explore the effect of minocycline hydrochloride in treatment of mycoplasmal pneumonia. Methods90 cases in hospital were randomly divided into treatment group and control group.42 cases received Azithromycin in control group,48 cases received minocyclme hydrochloride for oral use in foundation of control group,theraper than 85.7% in control group.The clinical indices of the treatment group were better than those of control group;and their differences were statistically significant(P＜0.05). ConclusionMinocycline hydrochloride could elevate mycoplasmal pneumonia therapeutic efficacy,the method could offer a quick action with good result and lower adverse reaction.It worth be widely used in clinic.
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OBJECTIVE:To establish an HPLC method for determining the content of main components in minocycline hydrochloride sustained-release tablets.METHODS:The sample was separated on ODS-C_(18)column with the mobile phase consisted of 0.2 mol?L~(-1)ammonium oxalate-0.01 mol?L~(-1)edetate disodium-dimethylformamide-tetrahydrofuran (600:180:120:80)at a flow rate of 1.5 mL?min~(-1).The detection wavelength was set at 280 nm and the sample volume was 20?L.RESULTS:The linear range of minocycline was 0.05～0.5 mg?mL~(-1)(r=0.999 8)and the average recovery was 99.11%,RSD=0.5%.CONCLUSIONS:This method was proved to be accurate and reliable,sensitive and reproducible,and it can be used for determining the content of this tablets.
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Objective:To evaluate the therapeutic effect of minocycline hydrochloride on chronic periodontitis.Methods:150 teeth of 75 patients dagnosed as chronic periodontitis were divided as test group(75 teeth treated by minocycline hydrochloride) and control group(75 teeth treated by 20g/L iodoglycerin).The effect of medicines were evaluated by clinical symptom combined with gingival index and the depth of pocket which were examined before and after treatment.Results:The baseline data of two groups indicated equilibrium.The status aroud the tested teeth in test group were improved,which was better than control group after 4-week treatment.The therapeutic effect of minocycline hydrochloride was better than iodoglycerin and there was statistic difference(P