Patent Application
20190343874
The present invention is related to a drug prepared by a nickel complex, and more particularly related to a use of a nickel complex in preparing drugs for relieving inflammation.
Reactive oxygen species (ROS), such as superoxide anion (O2−), hydrogen peroxide (H2O2), hypochlorous acid (HOCl) and the like, play an essential role in human's immune system which could remove bacteria and infected cells to keep people away from diseases. However, an excessive amount of reactive oxygen species would result in oxidative damage to the human body. For example, reactive oxygen species may stimulate inflammation cells and induce inflammatory response or damage blood vessels, etc.
Under normal physiological conditions, reactive oxygen species would be generated through a catalytic reaction of phagocyte with related enzymes. Besides, the chemicals existed in external environment also could induce the formation of reactive oxygen species. For example, para-phenylenediamine (PPD) is commonly used as one of the ingredients of hair dyes, and has also been used as a pigment in Henna Tattoo body art by some immoral traders. However, para-phenylenediamine is very harmful to human health since it could induce the formation of reactive oxygen species in the cells such as keratinocyte, germ cells, urothelial epithelial cells, and kidney cells, and cause bladder inflammation, bladder dysfunction, and even bladder cancer.
In view of the above, an object of the present invention is to provide a use of a nickel complex in preparing drugs for relieving inflammation so as to relieve inflammatory response.
According to the present invention, the use of a nickel complex in preparing drugs for relieving inflammation includes a nickel complex having at least one of a structural formula (I) and a structural formula (II):
wherein, L is a solvent molecule.
The advantage of the present invention in that the nickel complex has a similar reactivity with the active site of nickel-containing superoxide dismutase (NiSOD), which could remove reactive oxygen species, such that the nickel complex could be used to prepare drugs for relieving inflammation.
The present invention will be best understood by referring to the following detailed description of some illustrative embodiments in conjunction with the accompanying drawings, in which
The following illustrative embodiments and drawings are provided to illustrate the disclosure of the present invention, these and other advantages and effects can be clearly understood by persons skilled in the art after reading the disclosure of this specification. According to an embodiment of the present invention, a nickel complex for preparing drug of relieving inflammation has at least one selected from a group consisting of the following structural formula (I) (hereinafter, referred to as WCt003), and the following structural formula (II) (hereinafter, referred to as WCt006):
In the abovementioned structural formula, L is a solvent molecule, such as water, acetonitrile, ethanol, tert-butyl isocyanate, etc., however, this is not a limitation of the present invention.
The manufacturing method of the nickel complexes WCt003 and WCt006 has been disclosed in U.S. Pat. No. 8,642,763 and will not be described in detail herein.
Since the nickel complexes WCt003 and WCt006 respectively have a similar reactivity with the active site of nickel-containing superoxide dismutase (NiSOD), which could remove reactive oxygen species, WCt003 and WCt006 could be used to prepare drugs for relieving inflammation, especially for reducing reactive oxygen species in body fluid to relieve a bladder inflammation caused by reactive oxygen species. In the following description, several animal experiments were performed to evaluate a relieving inflammation effect of the drugs prepared from WCt003 and WCt006, wherein the animal experiments include administrating the experimental animals with para-phenylenediamine (PPD) to increase an in vivo count of reactive oxygen species, and then administrating the experimental animals with the drug prepared from WCt003 and WCt006.
In the current embodiment, 24 adult female Wistar rats were adopted as the experimental animals in the animal experiments and were randomly divided into four groups to be treated with different intraperitoneal injections. Referring to Table 1, the four groups are as follows: 1) the control group: 1 mL/day saline solution for 4 weeks; 2) the first experimental group: PPD (60 ∞g/kg/day) for 4 weeks; 3) the second group: PPD (60 g/kg/day) for 4 weeks and a drug (1.5 mg/kg/day) prepared from WCT003 for the last 2 weeks of; 4) the third experimental group: PPD (60 μg/kg/day) for 4 weeks and a drug (1.5 mg/kg/day) prepared from WCT006 for the last 2 weeks.
As shown in
Referring to Table 2, which lists the sample data collected from the rats of the control group and the first experimental group where were placed in the metabolic cage:
It could be known from Table 2 that the urinary frequency of the rats of the first experimental group is more frequent than the rats of the control group, and the rats of the first experimental group also had more urine and stool.
Then, each group of the rats were anesthetized with urethane (1.2 g/kg) via percutaneously injection, and a catheter was placed in a left femoral artery of each of the rats to measure arterial pressure (ABP). Meanwhile, intravesical pressure of the rats were also measured to obtain the parameters such as bladder intercontraction interval (ICI), urination time (MT), maximum urination pressure (MVP), contraction amplitude (A=MVP-BP), urination pressure threshold (PT), etc., as shown in
Referring to Table 3, which lists the parameters obtained from measuring intravesical pressure of each group of the rats:
It could be known from Table 3 and
To determine the effect of the drug prepared from the nickel complex WCt003 and WCt006 on eliminating reactive oxygen species, a luminol and lucigenin chemiluminescence (CL) method was utilized. The method includes the following steps: 0.2 ml sample of blood or urine was mixed with 0.5 ml of 1 mmol/L lucigenin or 0.2 mmol/L luminol, and then the mixture was analyzed with a chemiluminescence analysis system, wherein, the recorded signals were corresponding to the hydrogen peroxide (H2O2) and hypochlorous acid (HOCl) count in the luminol method, while the recorded signals were corresponding to the superoxide anion (O2−) count in the lucigenin method.
As shown in
Referring to
From the aforementioned experimental results, it could be seen that the nickel complexes WCt003 and WCt006 could be used to prepare the drugs for relieving inflammation, which could alleviate bladder inflammation, and eliminate reactive oxygen species, such as relieving inflammatory response caused by superoxide anion (O2−), hydrogen peroxide (H2O2), singlet oxygen (1O2), hypochlorous acid (HOCl), nitrogen monoxide (NO), nitrogen dioxide (NO2), etc.
The count of WCt003 or WCt006 in the drug used in the above experiments is 1.5 mg/kg, however, this is not a limitation of the present invention. In other embodiments, the WCt003 or WCt006 count could be between 0.15 mg/kg to 15 mg/kg and the effect of relieving inflammation could be achieved. Preferably, the WCt003 or the WCt006 count could be between 0.5-2.5 mg/kg.
In the aforementioned experiments, the drugs prepared from WCt003 and WCt006 were treated via intraperitoneal injection (intraperitoneally administered), however, this is not a limitation of the present invention. Other types of treatment such as transdermal administration, oral administration bladder irrigation, etc. also could be utilized.
In summary, the nickel complexes WCt003 and WCt006 could be used to prepare the drugs for relieving inflammation, which could reduce the voiding frequency caused by bladder inflammation and eliminate the reactive oxygen species.
It must be pointed out that the embodiments described above are only some embodiments of the present invention. All equivalent structures which employ the concepts disclosed in this specification and the appended claims should fall within the scope of the present invention.
| Number | Date | Country | Kind |
|---|---|---|---|
| 107115858 | May 2018 | TW | national |
