CN114344328A - Composition for reducing risk of gout of hypertension patient - Google Patents
Composition for reducing risk of gout of hypertension patient Download PDFInfo
- Publication number
- CN114344328A CN114344328A CN202011084152.6A CN202011084152A CN114344328A CN 114344328 A CN114344328 A CN 114344328A CN 202011084152 A CN202011084152 A CN 202011084152A CN 114344328 A CN114344328 A CN 114344328A
- Authority
- CN
- China
- Prior art keywords
- magnesium
- composition
- folic acid
- active ingredient
- parts
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 68
- 206010020772 Hypertension Diseases 0.000 title claims abstract description 50
- 201000005569 Gout Diseases 0.000 title claims abstract description 30
- 230000001603 reducing effect Effects 0.000 title claims abstract description 24
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 claims abstract description 57
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 claims abstract description 55
- 229940116269 uric acid Drugs 0.000 claims abstract description 55
- 239000008280 blood Substances 0.000 claims abstract description 23
- 210000004369 blood Anatomy 0.000 claims abstract description 23
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims description 106
- 239000011777 magnesium Substances 0.000 claims description 81
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 80
- 229910052749 magnesium Inorganic materials 0.000 claims description 80
- 239000011724 folic acid Substances 0.000 claims description 54
- 235000019152 folic acid Nutrition 0.000 claims description 54
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims description 52
- 229960000304 folic acid Drugs 0.000 claims description 52
- 239000000284 extract Substances 0.000 claims description 22
- 201000001431 Hyperuricemia Diseases 0.000 claims description 21
- 235000014441 Prunus serotina Nutrition 0.000 claims description 21
- 241001412173 Rubus canescens Species 0.000 claims description 21
- 239000004480 active ingredient Substances 0.000 claims description 21
- 230000001631 hypertensive effect Effects 0.000 claims description 20
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 8
- 150000002224 folic acids Chemical class 0.000 claims description 5
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical group [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 4
- 239000001095 magnesium carbonate Substances 0.000 claims description 4
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 4
- 235000019341 magnesium sulphate Nutrition 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 208000000913 Kidney Calculi Diseases 0.000 claims description 3
- 206010029148 Nephrolithiasis Diseases 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 235000005911 diet Nutrition 0.000 claims description 3
- 230000002496 gastric effect Effects 0.000 claims description 3
- 238000001727 in vivo Methods 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- 229940105150 5-methyltetrahydrofolic acid Drugs 0.000 claims description 2
- 206010018634 Gouty Arthritis Diseases 0.000 claims description 2
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 claims description 2
- KVUAALJSMIVURS-ZEDZUCNESA-L calcium folinate Chemical compound [Ca+2].C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC([O-])=O)C([O-])=O)C=C1 KVUAALJSMIVURS-ZEDZUCNESA-L 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 238000013270 controlled release Methods 0.000 claims description 2
- 230000007797 corrosion Effects 0.000 claims description 2
- 238000005260 corrosion Methods 0.000 claims description 2
- 230000008021 deposition Effects 0.000 claims description 2
- 230000000378 dietary effect Effects 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 claims description 2
- ZNOVTXRBGFNYRX-ABLWVSNPSA-N levomefolic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 ZNOVTXRBGFNYRX-ABLWVSNPSA-N 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 239000000395 magnesium oxide Substances 0.000 claims description 2
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 2
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 2
- 229940065207 methylfolic acid Drugs 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000006188 syrup Substances 0.000 claims description 2
- 235000020357 syrup Nutrition 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims 1
- 208000017169 kidney disease Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 description 29
- 241000700159 Rattus Species 0.000 description 16
- 230000002195 synergetic effect Effects 0.000 description 13
- 239000003814 drug Substances 0.000 description 8
- 229940079593 drug Drugs 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 230000002269 spontaneous effect Effects 0.000 description 6
- 235000015097 nutrients Nutrition 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 238000011552 rat model Methods 0.000 description 3
- 208000007530 Essential hypertension Diseases 0.000 description 2
- 206010046337 Urate nephropathy Diseases 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 229940014144 folate Drugs 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 208000030159 metabolic disease Diseases 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- 208000037157 Azotemia Diseases 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- 208000002330 Congenital Heart Defects Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- -1 L-methylfolic acid Chemical compound 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 208000026816 acute arthritis Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 235000008207 calcium folinate Nutrition 0.000 description 1
- 239000011687 calcium folinate Substances 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 208000028831 congenital heart disease Diseases 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000035487 diastolic blood pressure Effects 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 208000016097 disease of metabolism Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 229960002293 leucovorin calcium Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000000250 revascularization Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 208000009852 uremia Diseases 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The composition has the support of clinical evidence-based medical evidence, can reduce the blood uric acid level of a hypertension patient and prevent the rise of blood uric acid, thereby reducing the risk of gout occurrence, and can be used for preventing gout complications of the hypertension patient.
Description
Technical Field
The invention relates to a composition for reducing gout occurrence risk of a hypertension patient, and belongs to the field of medicines.
Background
The purine substances are subjected to long-term metabolic disorder and disorder in vivo, so that the concentration of a metabolite uric acid in blood is continuously increased, urate crystals are formed after the purine substances are supersaturated, and the urate crystals are deposited on tissues such as joints, kidneys and cartilages to cause tissue damage, namely gout, which belongs to metabolic related diseases. The clinical characteristics of gout are hyperuricemia, tophaceous deposit, repeated attack of gouty acute arthritis, characteristic chronic arthritis and joint deformity, which often involve the kidney, cause gouty nephropathy, uric acid kidney stones and even uremia, and seriously threaten the life of patients.
Blood uric acid levels are affected by a variety of factors including age, sex, race, genetics, dietary habits, drugs, and environment. Survey data show that the prevalence rate of Hyperuricemia (HUA) in recent years in China generally shows a growing trend, wherein 9.2-26.2% for men and 0.7-10.5% for women. Chinese multiple disciplines of diagnosis and treatment of hyperuricemia related diseases are commonly known. 2017. Gout has become the second most metabolic disease in China after diabetes. The increase in gout incidence is associated with an increase in living standard, a change in dietary structure, poor living habits, and the like, and tends to be low-aged.
According to the investigation, the prevalence rate of hyperuricemia in the essential hypertension patients is 30-35%, and particularly, the increase of the blood uric acid in the untreated hypertension patients can reach about 58%. [ Lin Jian, Xieliang, hypertension complicated with hyperuricemia clinical problem, journal of Chinese Utility medicine, 2011 ]. The increase of the basic blood uric acid level is also an independent predictor of the onset of hypertension, so that the uric acid level of hypertension patients or susceptible people should be controlled, and the gout can be prevented.
Based on the unexpected discovery in scientific research, the invention provides a safe and effective composition capable of reducing the risk of gout complications for hypertension patients, and meets the clinical requirements.
Disclosure of Invention
The invention aims to solve the potential gout occurrence risk of hypertension, and discloses a composition for reducing the gout occurrence risk of a hypertension patient.
In order to realize the purpose of the invention, the invention adopts the following technical scheme:
a composition for reducing risk of gout occurrence in hypertensive patients comprises a)50-550 parts of magnesium-containing active ingredient calculated by magnesium content, and b)0.05-0.8 part of folic acid or derivatives thereof.
The composition of the invention preferably comprises 500 parts of magnesium-containing active ingredient and 0.2-0.8 part of folic acid or derivatives thereof, wherein the magnesium-containing active ingredient is calculated by magnesium content.
In the present invention, when the blood magnesium concentration of the hypertensive is less than 819. mu. mol/L, it is preferable that the magnesium-containing active ingredient in the composition provided by the present invention is 50 to 120 parts and folic acid or a derivative thereof is 0.6 to 0.8 part, in terms of magnesium content.
In the present invention, when the blood magnesium concentration of the hypertensive is 819. mu. mol/L or more, it is preferable that the magnesium-containing active ingredient in the composition provided by the present invention is 150-450 parts and folic acid or a derivative thereof is 0.2-0.5 part, in terms of magnesium content.
The composition of the invention also comprises 200-1000 parts of black cherry extract; preferably, the content of the black cherry extract is 400-800 parts.
The composition of the invention, the folic acid derivative is selected from one or more of 5-methyltetrahydrofolic acid, leucovorin calcium, L-methylfolic acid, folate, active metabolites of folic acid or folate and substances capable of releasing/generating folic acid in vivo.
The composition of the invention comprises magnesium-containing active ingredients selected from magnesium carbonate, magnesium oxide, magnesium sulfate and natural extracts with high magnesium content.
The composition of the invention also comprises edible or medicinal acceptable excipient or carrier or mixture thereof.
The composition of the present invention can be administered by, but not limited to, oral, gastrointestinal, topical, transdermal, intravenous, intramuscular, inhalation, etc.
The composition of the present invention may be in the form of, but not limited to, tablets, capsules, corrosion inhibitors, controlled release agents, liquids, syrups, powders, and the like.
The composition is used for preparing a product for reducing gout occurrence risk of hypertension patients, and the gout occurrence risk preferably comprises hyperuricemia, tophus deposition, gouty arthritis, gouty nephropathy, uric acid renal calculus and the like.
The use according to the present invention is characterized in that the hypertensive patient is hypertension accompanied by homocysteine elevation.
In the application, when the blood magnesium concentration of a hypertensive is lower than 819 mu mol/L, the effect of reducing the gout occurrence risk of the hypertensive is remarkably stronger by 50-120 parts of a composition consisting of a magnesium-containing active ingredient and 0.6-0.8 part of folic acid or a derivative thereof in terms of magnesium content than by other contents of the composition, and the composition has remarkable synergistic effect among the components, so that the composition is a more excellent composition for reducing the gout occurrence risk of the hypertensive.
In the application of the invention, when the blood magnesium concentration of a hypertensive is equal to or higher than 819 mu mol/L, the effect of the composition consisting of 150-450 parts of magnesium-containing active ingredient and 0.2-0.5 part of folic acid or derivatives thereof in terms of magnesium content on reducing the gout occurrence risk of the hypertensive is remarkably stronger than that of the composition with other content, and the composition has remarkable synergistic effect among the components, so that the composition is a more excellent composition for reducing the gout occurrence risk of the hypertensive.
In the present invention, "risk" relates to the probability that an event occurs within a particular time period, and may mean an "absolute" risk or a "relative" risk of a subject. The absolute risk may be measured with reference to actual observations after measurements on the relevant time group or with reference to index values generated from a statistically valid historical group of already followed up relevant epochs. Relative risk refers to the ratio of the absolute risk of a subject compared to the absolute risk of a low risk group or the average group risk, which may vary with the manner in which the clinical risk factors are evaluated.
The composition has the advantages that the composition is supported by clinical evidence-based medical embodiment, and provides the composition for reducing the risk of gout occurrence of the hypertension patient by analyzing the data of large samples of nutrients and the risk of gout occurrence in the hypertension patient and combining with animal pharmacological research. The composition provided by the invention has the function of reducing the risk of gout occurrence of hypertension patients, the effect of the composition consisting of the magnesium-containing active ingredient and the folic acid or the derivatives thereof is obviously better than the single application effect of the magnesium-containing active ingredient or the folic acid or the derivatives thereof in the composition, and the components of the composition show unexpected synergistic effect. The invention also provides compositions consisting of the magnesium-containing active ingredient and the folic acid or the derivatives thereof with different contents particularly aiming at different hypertension patients, namely the compositions consisting of the magnesium-containing active ingredient and the folic acid or the derivatives thereof are provided according to different blood magnesium levels of the hypertension patients, and the compositions can exert the optimal drug effect on the basis of embodying accurate treatment. The compositions provided herein may also comprise black cherry extract. The composition containing the black cherry extract is a composition which can more effectively reduce the gout occurrence risk of the hypertension patient, and the effect of the composition consisting of the three components is obviously stronger than that of the composition consisting of the black cherry extract or the magnesium active component and the folic acid, so that the three components have synergistic effect, and the composition is more suitable for reducing the gout occurrence risk of the hypertension patient.
Detailed Description
The specific embodiments described herein are merely illustrative of the invention and do not delimit the invention.
Example 1: influence of different doses of magnesium and folic acid on uric acid level change of hypertensive rats
Method and device
The experiment adopts middle-aged and elderly Spontaneous Hypertension Rats (SHR), SPF level, 40 +/-2 weeks old, female and male half, purchased from Beijing vitamin Tonglihua, and incorporated into the experiment after passing inspection. Blood was collected from orbital venous plexus, centrifuged, and serum uric acid (70.12 ± 18.64) μmol/L was measured using a full-automatic biochemical immunoassay analyzer, 130 rats were selected, randomly divided into 12 groups of 10 to 11 rats according to uric acid level, administered at the dose shown in table 1 (magnesium sulfate was used, the dose was measured as magnesium) once a day, and administered at a gavage volume of 10ml/kg for 20 weeks.
Table 1: uric acid levels after termination of administration in groups of Spontaneously Hypertensive Rats (SHR) ((S))
n＝10-11)
P <0.05, P <0.01 compared to SHR group.
Second, result in
In combination with the above experimental results, it can be seen from Spontaneous Hypertensive Rats (SHR) in the SHR control group that the spontaneous hypertensive rats show an increase in uric acid levels over time, which is consistent with the literature and the epidemiological survey results (essential hypertension is often accompanied by the occurrence of hyperuricemia).
As can be seen from the above table 1, the nutrients Mg and folic acid used singly in different dosage groups have certain effect of inhibiting the increase of uric acid, and similar uric acid reducing effect can be obtained when magnesium is supplemented above 15Mg/kg (P values are all less than 0.05). The combination of the dual nutrients in each dose has better effect of inhibiting the increase of uric acid. Table 1 shows that the combination of lower dose magnesium (e.g. 5mg/kg) and higher dose folic acid (e.g. 0.08mg/kg) shows better effect of inhibiting uric acid increase, the combination of magnesium and folic acid of 15-55mg/kg has closer effect of inhibiting uric acid increase (P values are all less than 0.01), wherein the combination of the higher dose magnesium and folic acid of 55mg/kg inhibits uric acid increase by a value slightly higher than that of the combination of folic acid of higher dose.
The method for estimating the effect of combining two medicines by using the 'Jinzheng' Q value method [ Jinzheng, Zhang laugh, equal probability and curve and Q5E-is also known as probability addition method, according to the pharmacological action of two medicines combined and the pharmacological action of two medicines used separately in the dose-effect curve region, the following formula is used to calculate Q ═ E (A + B)/(EA + EB-EA), the generation table in the formula is 'actually measured combining effect', the denominator is 'expected combining effect', and Q is the ratio of the two medicines. The combination of two drugs is considered antagonistic when Q <0.85, additive when Q <1.15 and synergistic when Q > 1.15.
The calculation of the effect analysis among the dose groups according to the above formula is as follows:
table 2: effect analysis of different dosage groups of magnesium and folic acid and single use of magnesium and folic acid on uric acid index
The results in table 2 show that the Q values of the 2, 3 and 5 dose groups are all greater than or equal to 1.15 when the magnesium and the folic acid are used together, which indicates that the magnesium and the folic acid have better synergistic effect of inhibiting the increase of uric acid compared with the magnesium and the folic acid which are used alone. The magnesium and folic acid (15+0.04) mg/kg group has the strongest synergistic effect, the lower-dose magnesium and the higher-dose folic acid (5+0.08) mg/kg have better synergistic effect, the magnesium and the folic acid with lower dose show better synergistic effect when the magnesium is more than 15m/kg, and the magnesium and the folic acid only show additive effect when the magnesium and the folic acid are both in large dose. In summary, from the results obtained in tables 1-2, it can be seen that the combination of lower doses of magnesium and higher doses of folic acid shows better synergistic effect in inhibiting uric acid increase; the combination of magnesium (15-55mg/kg) with higher dose and folic acid with lower dose has good effect of reducing uric acid and shows better synergistic effect; increasing the doses of magnesium and folic acid did not further reduce uric acid levels and the synergy between the two was reduced.
Example 2: effect of the composition of the present invention on uric acid levels in Spontaneous Hypertension (SHR) hyperuricemic rat model
Method and device
Spontaneous hypertension with hyperuricemia rat model: spontaneous Hypertensive Rats (SHR), SPF grade, sex half, 14-15 weeks old, purchased from Beijing Wintolite, and taken into the experiment after passing the inspection.
All spontaneously hypertensive rats were fed with a high-purine diet (prepared as follows) for 8 consecutive weeks, and 10 SHR rats were additionally fed with a normal diet as an SHR control group. All rats had free access to water.
Preparing high-purine feed: mixing yeast dry powder and adenine with 10% and 0.1% respectively, adding into pulverized rat pellet feed, and re-granulating to obtain high purine feed.
After the model building is finished, all rats are collected from orbital venous plexus, centrifuged, the uric acid level of the rats is measured by using a full-automatic biochemical immunoassay analyzer, and selected SHR rats successfully built are randomly divided into 7 groups according to the body weight and the uric acid level, wherein each group comprises 9-10 SHR rats. The following formulations (magnesium carbonate is used as magnesium carbonate, and the dosage is measured by magnesium content) are respectively adopted for gastric lavage administration: the volume of the gavage is 10ml/kg once a day. The SHR control group and the model group were administered with the same volume of purified water and were continuously gavaged for 8 weeks. After the experiment, the uric acid level is measured by the same method after blood collection.
Table 3: uric acid, phosphorus, magnesium and folic acid levels change after administration to rats of each group: (
n＝9-10)
In comparison with the set of SHR's,#P<0.05，##P<0.01; comparison with model group<0.05，**P<0.01; compared with the magnesium + folic acid 1 group,&P<0.05，&&P<0.01; compared with the magnesium + folic acid 2 group,※P<0.05，※※P<0.01; compared with black cherry extract (80mg/kg),§§P<0.01; compared with black cherry extract (40mg/kg),⊕⊕P<0.01。
second, result in
The experimental result shows that the black cherry extract, the magnesium and the folic acid have better effect of reducing uric acid of a rat model with hyperuricemia (P is less than 0.05), and the black cherry extract, the magnesium and the folic acid have more obvious effect of reducing uric acid (P is less than 0.01) compared with the black cherry extract or the magnesium and folic acid when being combined and applied.
The effect of black cherry extract + (magnesium + folic acid) composition on uric acid reduction was calculated using the same Q-value calculation as in example 1, and the results are as follows:
table 4: analysis of Effect of the composition of the invention on rat uric acid index
The black cherry natural extract has the effect of reducing uric acid by being used alone and is combined with the nutrient disclosed by the invention, and the Q values of the two dosage compositions are more than or equal to 1.15, so that the black cherry extract and the nutrient have the synergistic effect of reducing uric acid. Both groups of compositions containing black cherry extract had significant uric acid lowering effect, and the low dose combination of black cherry had better synergistic effect (greater Q value).
Example 3 Effect of the compositions of the present invention on uric acid levels in patients with hypertension and hyperuricemia
Method and device
The hypertension patients of 45-75 years old who are eligible participants are selected from a hypertension follow-up queue maintained in the past, and are defined as that the resting systolic pressure is more than or equal to 140mmHg or the diastolic pressure is more than or equal to 90mmHg when the patients are screened and recruited, or the patients are taking antihypertensive drugs. The primary exclusion criteria included a history of stroke, a history of Myocardial Infarction (MI), a history of heart failure, a history after revascularization of coronary arteries, and/or a history of congenital heart disease as diagnosed by a physician.
Measuring the baseline plasma magnesium and Uric Acid (UA) concentrations, selecting patients with hyperuricemia (male UA concentration is more than or equal to 417 mu mol/L, female UA concentration is more than or equal to 357 mu mol/L), randomly dividing the blood magnesium concentration into three groups according to the condition that the blood magnesium concentration is less than 819 mu mol/L, administering a placebo to one group, administering 400mg of black cherry extract and 50mg of magnesium (magnesium sulfate agent, calculated by magnesium, the same below) +0.8mg of folic acid to the other group, and administering 400mg of black cherry extract and 150mg of magnesium and 0.4mg of folic acid to the other group; the blood magnesium concentration is more than or equal to 819 mu mol/L, and the administration mode is the same as the mode of the blood magnesium concentration less than 819 mu mol/L. . The study period was 8 weeks, with hyperuricemia cure rates observed primarily (UA concentrations < 417 μmol/L in men and < 357 μmol/L in women), with the secondary outcome being a change in UA concentration, defined as UA on entry minus UA on exit.
Second, result in
TABLE 5 Effect of the compositions of the present invention on the treatment of hyperuricemia and varying levels of uric acid
Compared with the corresponding placebo group,##P<0.01 or**P<0.01。
The analysis results show that when the blood magnesium concentration of the patient suffering from the hypertension with the hyperuricemia is less than 819 mu mol/L, the uric acid level can be greatly reduced by supplementing the combination of the folic acid with higher dose, the magnesium with small dose and the black cherry extract, the uric acid level of 58% of the patients suffering from the hyperuricemia can be reduced to be below the diagnostic standard of the hyperuricemia, and compared with the combination of the folic acid with lower dose and the magnesium with higher dose, the uric acid level reducing agent has an improved effect, but the uric acid reducing agent has a better treatment effect on the hyperuricemia; when the blood magnesium level is more than 819 mu mol/L, the combination of magnesium with higher dose, folic acid with small dose and the black cherry extract can be supplemented to greatly reduce the uric acid level, the uric acid level of 45 percent of patients with hyperuricemia can be reduced to be below the diagnostic standard, and the effect is improved compared with the effect of the combination of magnesium with lower dose and folic acid with larger dose, but the effect is not as good as the effect of the former combination for reducing the uric acid to treat the hyperuricemia.
Claims (15)
1. A composition for reducing gout occurrence risk of hypertension patients comprises a)50-550 parts of magnesium-containing active ingredient calculated by magnesium content, and b)0.05-0.8 part of folic acid or derivatives thereof.
2. The composition as claimed in claim 1, wherein the magnesium-containing active ingredient is 100 parts and the folic acid or the derivative thereof is 0.2 to 0.8 part.
3. The composition according to claim 1, wherein the magnesium-containing active ingredient is 50 to 120 parts and the folic acid or the derivative thereof is 0.6 to 0.8 part when the blood magnesium concentration of the hypertensive is less than 819. mu. mol/L.
4. The composition as claimed in claim 1, wherein the magnesium-containing active ingredient is 150-450 parts and the folic acid or the derivative thereof is 0.2-0.5 part when the blood magnesium concentration of the hypertensive is 819 μmol/L or higher.
5. Composition according to any one of claims 1 to 4, characterized in that it further comprises other active ingredients, preferably 200 and 1000 parts of black cherry extract; more preferably, the active ingredient is 400-800 parts of black cherry extract.
6. A composition according to any one of claims 1 to 4, wherein the folic acid derivative is selected from the group consisting of 5-methyltetrahydrofolic acid, calcium leucovorin, L-methylfolic acid, folic acid salts, folic acid or an active metabolite of folic acid and substances that release/generate folic acid in vivo.
7. The composition according to any one of claims 1 to 4, wherein the magnesium-containing active ingredient is selected from magnesium carbonate, magnesium oxide, magnesium sulfate, and natural extracts with high magnesium content.
8. The composition according to any one of claims 1 to 7, further comprising a dietary or pharmaceutically acceptable excipient or carrier or mixture thereof.
9. The composition of any one of claims 1-7, wherein the composition is administered orally, gastrointestinal, topically, transdermally, intravenously, intramuscularly, by inhalation, or the like.
10. The composition according to any one of claims 1 to 7, wherein the composition is in the form of tablets, capsules, corrosion inhibitors, controlled release agents, liquids, syrups, powders and the like.
11. Use of a composition according to any one of claims 1 to 7 in the manufacture of a product for reducing the risk of gout development in hypertensive patients.
12. The use according to claim 11, wherein said risk of gout development comprises hyperuricemia, tophus deposition, gouty arthritis, gouty kidney disease, uric acid kidney stones, and the like.
13. The use according to claim 11, wherein the hypertensive patient is hypertension with elevated homocysteine.
14. The use according to any one of claims 11 to 13, wherein the magnesium-containing active ingredient in the composition is 50 to 120 parts and the folic acid or the derivative thereof is 0.6 to 0.8 part when the blood magnesium concentration of the hypertensive is less than 819 μmol/L.
15. The use according to any one of claims 11 to 13, wherein the magnesium-containing active ingredient in the composition is 150-450 parts and the folic acid or the derivative thereof is 0.2-0.5 part when the blood magnesium concentration of the hypertensive is 819 μmol/L or higher.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011084152.6A CN114344328B (en) | 2020-10-12 | 2020-10-12 | Composition for reducing gout occurrence risk of hypertensive patient |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011084152.6A CN114344328B (en) | 2020-10-12 | 2020-10-12 | Composition for reducing gout occurrence risk of hypertensive patient |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114344328A true CN114344328A (en) | 2022-04-15 |
| CN114344328B CN114344328B (en) | 2024-01-16 |
Family
ID=81090277
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011084152.6A Active CN114344328B (en) | 2020-10-12 | 2020-10-12 | Composition for reducing gout occurrence risk of hypertensive patient |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114344328B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1350160A (en) * | 1971-06-29 | 1974-04-18 | Foremost Mckesson | Pharmaceutical compositions |
| CN102145010A (en) * | 2010-12-21 | 2011-08-10 | 李超群 | Use of combination of potassium and magnesium for preparing medicine for preventing or treating gout |
| CN104886581A (en) * | 2015-06-18 | 2015-09-09 | 上海善力健生物科技有限公司 | Biological agent for decreasing uric acid, treating gout and eliminating overnutrition and preparation method of biological agent |
| CN111588042A (en) * | 2019-12-23 | 2020-08-28 | 上海赋康健康管理有限公司 | Dietary nutrition conditioning food for assisting in reducing uric acid and controlling gout |
-
2020
- 2020-10-12 CN CN202011084152.6A patent/CN114344328B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1350160A (en) * | 1971-06-29 | 1974-04-18 | Foremost Mckesson | Pharmaceutical compositions |
| CN102145010A (en) * | 2010-12-21 | 2011-08-10 | 李超群 | Use of combination of potassium and magnesium for preparing medicine for preventing or treating gout |
| CN104886581A (en) * | 2015-06-18 | 2015-09-09 | 上海善力健生物科技有限公司 | Biological agent for decreasing uric acid, treating gout and eliminating overnutrition and preparation method of biological agent |
| CN111588042A (en) * | 2019-12-23 | 2020-08-28 | 上海赋康健康管理有限公司 | Dietary nutrition conditioning food for assisting in reducing uric acid and controlling gout |
Non-Patent Citations (1)
| Title |
|---|
| 李幼宝: "叶酸治疗对高血压患者血清尿酸水平、新发蛋白尿及蛋白尿相关死亡的影响", 中国博士学位论文全文数据库 医药卫生科技辑, vol. 1, no. 11, pages 062 - 108 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114344328B (en) | 2024-01-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2018371177B2 (en) | Dosage regimen of vidofludimus for use in the prevention or treatment of chronic inflammatory and/or autoimmune diseases | |
| CN106999461A (en) | Selective S1P1The dosage regimen of receptor stimulating agent | |
| WO2012050589A1 (en) | Methods for treating hyperuricemia and related diseases | |
| EP3290034A1 (en) | Use of trimethazine in preparation of drugs for preventing and treating liver diseases | |
| AU2018337933A1 (en) | Synthetic transdermal cannabidiol for the treatment of focal epilepsy in adults | |
| EP1539145A2 (en) | Method of treating tremors | |
| CA2855469A1 (en) | Compositions and methods for nutritional supplementation | |
| TW201016208A (en) | Methods of treatment of hyperuricemia and associated disease states | |
| WO2009093737A1 (en) | Anti-obesity pharmaceutical composition | |
| CN109833481B (en) | Medicinal composition of allisartan isoproxil or salt thereof and diuretic | |
| CN114344328A (en) | Composition for reducing risk of gout of hypertension patient | |
| US9271948B2 (en) | Agent for improving vesicourethral dyssynergia | |
| JP5984328B2 (en) | Independent Kakkonto extract combination agent | |
| EP3332779B1 (en) | Ameliorating agent for detrusor hyperactivity with impaired contractility | |
| JP4585186B2 (en) | Novel preventive or therapeutic agent for obesity, diabetes and abnormal lipid metabolism | |
| JP6454436B1 (en) | Medicine containing pemafibrate | |
| CN1299676C (en) | Anti-anoxia medicinal composition | |
| CN115715191B (en) | Therapeutic agent for urination symptom | |
| JP4974255B2 (en) | Combination of angiotensin II receptor antagonist | |
| CN112569356B (en) | A pharmaceutical composition containing diuretic | |
| CN115243774B (en) | Pharmaceutical composition containing amlodipine, chlorthalidone and amiloride | |
| CN113133997A (en) | Pharmaceutical composition containing berberine and application thereof | |
| CN106176737A (en) | A kind of have synergistic active component and Febustat compositions thereof with antihyperuricemic disease drug | |
| WO2020169041A1 (en) | Pharmaceutical composition containing amlodipine, chlorthalidone and aldosterone receptor antagonists | |
| CN115721670A (en) | Composition for auxiliary prevention and treatment of chronic kidney diseases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |