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CCM+


10ml ampoule

Intravenous drop infusion for severe cases 40ml a day


INDICATIONS:


Upper respiratory tract infection
febrile disease
coma
hemiplegia in stroke pneumonia
cerebral trombosis
cerebral hemorrhage with above symptoms
acute promyelocytic leukemia


INGREDIENTS

Cholic acid
Concha Margaritifera
Hyodeoxycholic acid
Fructus Gardeniae
Cornu Bubali
Radix Isiatidis
Baicalin
Flos Lonericerae



RESEARCH

Effects of Shuanghuanglian and CCM+, two multi-components of traditional Chinese medicinal preparations, on human leukocyte function
CCM+ and Shuanghuanglian (SHHL) are two commonly used Chinese herbal preparations with reported antiinflammatory activity. The effects of these two preparations on the capacity of staphylococcal toxic shock syndrome toxin 1 (TSST-1) to stimulate the production of cytokines (IL-1β, IL-6, TNF-α, IFN-γ) and chemokines (MIP-1α, MIP-1β and MCP-1) by peripheral blood mononuclear cell (PBMC) was tested. We also evaluated their effect on LPS-stimulated NF-κB transcriptional activity in a THP-1 cell line, and on human monocyte chemotactic response to chemoattractants. Non-cytotoxic concentrations of CCM+ (0.12%) and SHHL (6˜120 μg) significantly inhibited production of cytokines and chemokines in a dose-dependent manner (P < 0.05). Both, CCM+ at 1:100 and SHHL at 60 μg/ml, markedly inhibited RANTES, MIP-1α, SDF-1α and fMLP induced human monocyte migration (P<0.05 or 0.01). CCM+ (1%) did not inhibit monocyte chemotaxis induced by super-or sub-optimal concentrations of fMLP (10-5, 10-6 and 10-10 M), but only inhibited chemotaxis induced by optimal concentrations of fMLP at 10-7, 10-8 and 10-9 M. QKL (0.1% or 1%) and SHHL(6 or 60 μg/ml) markedly inhibited LPS-induced NF-κB activity in THP-1 cells. The results suggested that the pharmacological basis for the anti-inflammatory effects of CCM+ and SHHL is the result of suppression of NF-κB regulated gene transcription, leading to suppressed production of proinflammatory cytokine and chemokine. Interference with leukocyte chemotaxis also contributes to the anti-inflammatory and immunomodulating effects of these medicinals. Identification of the responsible components in these two herbal preparations may yield compounds suitable for structural modification into potent novel drugs.
Life Sciences Volume 70, Issue 24, 3 May 2002, Pages 2897-2913, 10.1016/S0024-3205(02)01541-2
A research conducted by--

  • Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute-Frederick, Bldg 560, Rm 31-19, Fort Detrick, Frederick, MD, 21702-1201, USA
  • Intramural Research Support Program, SAIC Frederick, National Cancer Institute- Frederick, USA
  • Department of Immunology and Molecular Biology, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702-1201, USA


CCM+ injection in inducing cell apoptosis in human acute promyelocytic leukemia

Objective: To investigate the mechanism of CCM+ Injection in treating acute promyelocytic leukemia.
Methods: Using MTT technique, cell morphologic method, DNA gel electrophoresis and flow-cytometry to study the human acute promyelocytic leukemia (HL-60) cell apoptosis induced by CCM+ and its active principle.
Results: CCM+ and its active principle, Baicalin and hyodeoxycholic acid, showed strong cytotoxicity in inhibiting HL-60 cell, the Bezoar cholic acid showed a weaker effect. Apoptosis could be induced after being treated for 6 hrs by the former three principles, showing a typical apoptosis peak under flow-cytometry, but could not be induced by the latter one.
Conclusion: CCM+ could induce leukemia cell apoptosis in vitro, which may be one of the mechanisms of CCM+ in curing acute promyelocytic leukemia.
Zhongguo Zhong Xi Yi Jie He Za Zhi Vol. 21 Issue 11 Pg. 840-2 (Nov 2001) ISSN: 1003-5370 [Print] China

Influences of CCM+ Injection on neuron apoptosis and mitochondrial membrane potential
Objective: To observe the influences of CCM+ Injection on apoptosis of(hippocampal) neurons and mitochondrion membrane potential(MMP) in rat model of hypoxia-(hypoglycemia-)rexyenation(HHR).
Methods: Mitochondrion activity was detected by methyl(thiazolyl) tetrazolium test(MTT).The apoptosis percentage and MMP were detected by flow(cytometry),and the cytomorphological changes and neuron necrotic percentage were observed with(fluorescence) microscope.
Results: After hypoxia-hypoglycemia treating in rats for 5 hours and reoxygenation treating for , 12, 24 hours the apoptosis rate of neurons increased significantly.There were chromatinic coacervation,(karyorrhexis) and apoptotic bodies in neurons were observed cytomorphologically.The MMP and(mitochondrion) activity decreased significantly after reoxygenation for 3, 12, 24 hours, and decreased(further) along with the prolongation of reoxygenation. CCM+ Injection could decrease obviously percentage of neuron apoptosis and necrosis and increase MMP and mitochondrion activity with a significant difference(P<0.05~0.01) compared with the HHR group.
Conclusion: CCM+ Injection could inhibit the decrease of MMP induced by injury of hypoxia-hypoglycemia-reoxygenation,stabilize MMP,inhibit cell apoptosis and protect hippocampal neurons.
Journal of Beijing University of Traditional Chinese Medicine 2006-02, R285.5, cnki:ISSN:1006-2157.0.2006-02-007


Clinical study on acute upper respiratory tract infection treated with
Objective: To explore the effect of CCM+ injection in treating acute fever.
Methods: four hundred cases of acute upper respiratory tract infection were divided into three groups treated with CCM+ 120 ml/d, 160 ml/d and 200 ml/d respectively, and compared with a control group treated with lincomycin 1.8 g/d.
Results: The markedly effective rate of CCM+ was 84.14%, which was better than that of lincomycin (75.83%). The mean initial time of CCM+ (12.6 h) was shorter than that of lincomycin (17.6 h). Effect of CCM+ on patients with disease course within one day was better than that within 3 days. No significant difference revealed between effects in groups treated with different dosage of CCM+. The effect of CCM+ in lowering white blood cell count was similar to that of lincomycin. For patients with positive throat swab culture of pathogenic bacteria, CCM+ displayed good antibacterial action in vivo.
Conclusion: CCM+ is a highly effective with rapid action drug for treatment of acute respiratory infection.
Zhongguo Zhong Xi Yi Jie He Za Zhi Vol. 19 Issue 4 Pg. 212-4 (Apr 1999) ISSN: 1003-5370 [Print] China



Effects of CCM+ effective components on nuclear factor-kappa B (in vitro)
Objective: To establish an ischemia-reperfusion injury model of rat cerebral microvascular endothelial cells (MVECs) in vitro, and to explore the relationship between nuclear factor-kappa B (NF-kappaB) and the protective effects of CCM+ effective components (hyocholic acid, taurocholic acid, baicalin, jasminoidin, Pinctada martensii) on MVECs.
Methods: Brain MVECs of male rats were digested with trypsin and subcultured, then the content of MVECs was adjusted to 1x10 (5)/mL and the MVECs were divided into normal control group, untreated group, hyocholic acid group, taurocholic acid group, baicalin group, jasminoidin group, Pinctada martensii group and nimodipine group, with six holes in each group. Except for the normal control group, the MVECs in the other groups were exposed in oxygen and glucose deprivation (OGD) circumstance in vitro to simulate ischemia-reperfusion injury. Immunocytochemical staining and image analysis system were used to observe the expression of NF-kappaB protein.
Results: Under a light microscope, the nuclei of MVECs in the normal control group were blank. Staining intensity of NF-kappaB protein in the nucleus in the untreated group was much deeper than that in the endochylema, with NF-kappaB shifted to nucleus after activation; a small quantity of NF-kappaB protein were expressed in the border of nucleus next to endochylema in groups of CCM+ effective components, and the NF-kappaB protein expression was weaker than that in the untreated group. With the image analysis, we found that transmittance of nucleus and endochylema in the untreated group was significantly lower than that in the normal control group (P<0.01). Transmittance of nucleus and endochylema in the treated groups was higher than that in the untreated group (P<0.05, P<0.01).
Conclusion: CCM+ effective components have significant effect in inhibiting NF-kappaB protein transferring from endochylema to nucleus in vitro.
Zhong Xi Yi Jie He Xue Bao Vol. 7 Issue 2 Pg. 135-9 (Feb 2009) ISSN: 1672-1977 [Print] China


Therapeutic effect of CCM+ on the acute lung injury
Objective: To investigate the effect of CCM+ and Methylprednisolone (MP) injection alone or combined on the acute lung injury (ALI) induced by oleic acid in rabbits.
Methods: The rabbits were randomly divided into 11 groups: oleic acid group; control group; treatment groups including low, middle and high dosage groups of CCM+ and MP alone and combined, respectively. ALI model was established by i.v. oleic acid (0.05 mL x kg(-1)) in these groups, and then i.v. above drugs respectively, while in control group, the same volume of normal saline was given. The respiratory amplitude and rate were observed, and blood samples were taken from cervical artery for blood-gas analysis before and at 30, 60, 120 min after oleic acid or normal saline administration. At the end of experiment, the concentration of LDH, CAT and MDA in the lung tissue were measured and pathologic changes of lung tissue were observed microscopically.
Results: Compared with oleic acid group, the respiratory amplitude markedly enhanced (P < 0.05) and respiratory rate lowered (P < 0.05) in the low, middle and high dose groups of CCM+ and MP injection. On the 30 min of treatment, PaO2 increased significantly (P < 0.05) in the low and middle dose groups of combined CCM+ and MP injection; PaCO2 decreased markedly (P < 0.05) on the 120 min of treatment in each treatment group. The level of LDH significantly increased (P < 0.05), CAT and MDA decreased (P < 0.05) in the middle and high groups of CCM+ and MP injection. The low and middle dose groups of combined CCM+ and MP injection can alleviate the pathological changes induced by oleic acid.
Conclusion: The curative effect of the low dose group of combined CCM+ and MP for the ALI induced by oleic acid was better than CCM+ and MP alone, while the big dose groups of CCM+ and MP alone better than the combination at the same dosage.
Zhongguo Zhong Yao Za Zhi Vol. 30 Issue 10 Pg. 769-73 (May 2005) ISSN: 1001-5302 [Print] China


Stir-baked Fructus gardeniae (L.) extracts inhibit matrix metalloproteinases and alter cell morphology
Matrix metalloproteinases (MMPs) play vital roles in many pathological conditions, including cancer, cardiovascular disease, arthritis and inflammation. Modulating MMP activity may therefore be a useful therapeutic approach in treating these diseases. CCM+ is a popular Chinese anti-inflammatory formulation used to treat symptoms such as rheumatoid arthritis, acute hypertensive cerebral hemorrhage, hepatitis and upper respiratory tract infection. In this paper, we report that one of the components of CCM+, Fructus gardeniae, strongly inhibits MMP activity. The IC50 values for the primary herbal extract and water extract against MMP-16 were 32 and 27 μg/ml, respectively. In addition, we show that the herbal extracts influence HT1080 human fibrosarcoma cell growth and morphology. These data may provide molecular mechanisms for the therapeutic effects of CCM+ and herbal medicinal Fructus gardeniae.
Journal of Ethnopharmacology Volume 117, Issue 2, 8 May 2008, Pages 285-289, 10.1016/j.jep.2008.01.033


Administration of high-dose CCM+ inhibited TUNEL positive cells (p<0.05) and caspase-3 activity (p<0.05) at 1d following ICH, and reduced apomorphine-induced rotation at 1d (p<0.01), 7d, 14 d and 28 d (p<0.05), compared with the controls. However, CCM+ in a low or moderate dose had no such effect. CCM+ reduced brain damage of intracerebral hemorrhage through inhibiting apoptosis, which suggested a potential intervention for ICH patients.
J Ethnopharmacol. 2009 Sep 7;125(2):269-73. Epub 2009 Jul 4


CCM+ could decrease obviously percentage of neuron apoptosis and necrosis and increase MMP and mitochondrion activity with a significant difference(P<0.05~0.01) compared with the HHR group.Conclusion CCM+ Injection could inhibit the decrease of MMP induced by injury of hypoxia-hypoglycemia-reoxygenation,stabilize MMP,inhibit cell apoptosis and protect hippocampal neurons.
--NEURAL REGENERATION RESEARCH 2006 1(6) R3 O61

 
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