CN110090237B - Medicine for treating liver injury and bone injury caused by vitamin A poisoning and application thereof - Google Patents

Medicine for treating liver injury and bone injury caused by vitamin A poisoning and application thereof Download PDF

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CN110090237B
CN110090237B CN201910461200.XA CN201910461200A CN110090237B CN 110090237 B CN110090237 B CN 110090237B CN 201910461200 A CN201910461200 A CN 201910461200A CN 110090237 B CN110090237 B CN 110090237B
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曹冶
康润敏
谢晶
林毅
张先惠
廖党金
彭广能
钟志军
于吉锋
叶勇刚
叶健强
潘梦
肖璐
李兴玉
戴卓建
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Shandong Rendi Bioengineering Group Co ltd
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Abstract

The application provides a medicine for treating liver injury and bone injury caused by vitamin A poisoning and application thereof, belonging to the technical field of traditional Chinese medicine extracts. The medicine comprises herpetospermum pedunculosum seed ether extract and/or penthorum chinense pursh water extract. The application of the medicine in preparing the medicine for treating liver injury and bone injury caused by vitamin A poisoning can be effectively used for treating liver injury and bone injury caused by vitamin A poisoning and treating symptoms such as headache, nausea, vomit, desquamation, pain at the peripheral part of the tail end of long bones, skin itch, muscle stiffness and the like caused by vitamin A poisoning.

Description

Medicine for treating liver injury and bone injury caused by vitamin A poisoning and application thereof
Technical Field
The application relates to the technical field of traditional Chinese medicine extracts, in particular to a medicine for treating liver injury and bone injury caused by vitamin A poisoning and application thereof.
Background
Vitamin a (retinol) is an unsaturated monohydric alcohol having an ester ring, and is a nutrient essential for humans and animals. One of the most obvious phenomena of vitamin a deficiency is xerophthalmia, and in addition, vitamin a deficiency causes symptoms such as decreased immune function, hemoglobin anabolic disorder, reproductive disorders, and growth retardation in children. In recent years, with the development of socio-economic, the life of people is improved, and the phenomenon of vitamin a excess appears in the sight of people. Because vitamin A is fat-soluble and can not be discharged with urine, and is stored in the body, finally the toxic level is reached, and acute and chronic toxicity and teratogenic toxicity can be caused. Acute poisoning may cause symptoms such as headache, nausea, vomiting, desquamation, etc.; chronic poisoning causes symptoms such as pain at the peripheral part of the long bone end, skin itch, muscle stiffness and the like.
For vitamin a overload, the main treatment is to stop the intake of vitamin a-rich food immediately, so that the toxic symptoms are not intensified, but there is no good treatment.
Disclosure of Invention
The application aims to provide a medicine for treating liver injury and bone injury caused by vitamin A poisoning and an application of the medicine, and the medicine can be effectively used for treating liver injury and bone injury caused by vitamin A poisoning.
In a first aspect, the present application provides the use of a medicament comprising an ether extract of herpetospermum pedunculosum seeds and/or an aqueous extract of penthorum chinense pursh in the preparation of a medicament for treating liver injury and bone injury caused by vitamin a poisoning.
After the patient has developed symptoms of vitamin a poisoning, the patient takes a medicine prepared by using the chaenomeles speciosa ether extract or the penthorum chinense pursh water extract, and the symptoms of vitamin a poisoning of the patient are as follows: headache, nausea, vomiting, desquamation, pain in the peripheral part of the terminal long bones, skin itching, muscle stiffness and the like can be effectively relieved. If a patient takes a medicine prepared from the herpetospermum pedunculosum seed ether extract and the penthorum chinense pursh water extract, the toxic symptom of the patient is relieved more quickly, and the medicine can be effectively used for treating liver injury and bone injury caused by vitamin A poisoning.
In another embodiment in combination with the first aspect, the medicament comprises 4 to 6 parts by weight of the penthorum chinense pursh water extract and 0.5 to 2 parts by weight of the astragalus polysaccharide.
The astragalus polysaccharide can stimulate the autoimmunity of a human body, is used for preparing a medicine after being matched with the penthorum chinense pursh water extract according to the weight parts, and has better effect of treating liver injury and bone injury caused by vitamin A poisoning compared with the single penthorum chinense pursh water extract.
In another embodiment in combination with the first aspect, the medicament comprises 0.2-1 parts by weight of the pedunculate herpetospermum seed ether extract and 0.5-2 parts by weight of the astragalus polysaccharide.
The astragalus polysaccharide can stimulate the autoimmunity of a human body, is used for preparing a medicine after being matched with the herpetospermum pedunculosum seed ether extract according to the weight parts, and has better effect of treating liver injury and bone injury caused by vitamin A poisoning compared with the single herpetospermum pedunculosum seed ether extract.
In another embodiment in combination with the first aspect, the medicament comprises 4-6 parts by weight of the penthorum chinense pursh water extract and 0.2-1 part by weight of the herpetospermum pedunculosum seed ether extract.
The penthorum chinense pursh water extract and the pedunculate herpetospermum seed ether extract in parts by weight are used for preparing medicines, and compared with the single pedunculate herpetospermum seed ether extract or the single penthorum chinense pursh water extract, the penthorum chinense pursh water extract and the pedunculate herpetospermum seed ether extract have better effect of treating liver injury and bone injury caused by vitamin A poisoning.
With reference to the first aspect, in another embodiment, the medicament further comprises 0.5 to 2 parts by weight of astragalus polysaccharide.
The astragalus polysaccharide can stimulate the autoimmunity of a human body, is used for preparing a medicine after being matched with the penthorum chinense pursh water extract and the herpetospermum pedunculosum seed ether extract according to the weight parts, and has better effect of treating liver injury and bone injury caused by vitamin A poisoning compared with the mixture of the penthorum chinense pursh water extract and the herpetospermum pedunculosum seed ether extract.
In a second aspect, the present application provides a medicament for treating liver injury and bone injury caused by vitamin a poisoning, the medicament comprising 4-6 parts by weight of an aqueous extract of penthorum chinense pursh and 0.2-1 part by weight of an ether extract of herpetospermum pedunculosum seeds.
The penthorum chinense pursh water extract and the pedunculate herpetospermum seed ether extract in parts by weight are used for preparing medicines, and compared with the single pedunculate herpetospermum seed ether extract or the single penthorum chinense pursh water extract, the penthorum chinense pursh water extract and the pedunculate herpetospermum seed ether extract have better effect of treating liver injury and bone injury caused by vitamin A poisoning.
With reference to the second aspect, in another embodiment, the medicament further comprises 0.5 to 2 parts by weight of astragalus polysaccharide.
The astragalus polysaccharide can stimulate the autoimmunity of a human body, is used for preparing a medicine after being matched with the penthorum chinense pursh water extract and the herpetospermum pedunculosum seed ether extract according to the weight parts, and has better effect of treating liver injury and bone injury caused by vitamin A poisoning compared with the mixture of the penthorum chinense pursh water extract and the herpetospermum pedunculosum seed ether extract.
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In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings needed to be used in the embodiments are briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present application and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings can be obtained from the drawings without inventive efforts and also belong to the protection scope of the present application.
FIG. 1 is a line graph of the effect of various drugs on serum alanine Aminotransferase (ALT) in mice provided in the examples herein;
FIG. 2 is a line graph showing the effect of various drugs on serum aspartate Aminotransferase (AST) in mice provided in the examples of the present application;
FIG. 3 is a line graph of the effect of various drugs provided in the examples herein on serum calcium (Ca) in mice;
FIG. 4 is a line graph of the effect of various drugs on serum phosphorus (P) in mice provided in the examples herein;
FIG. 5 is a line graph of the effect of various drugs on the serum calcium to phosphorus ratio of mice provided in the examples of the present application;
FIG. 6 is a line graph of the effect of various drugs on serum alkaline phosphatase (ALP) in mice provided in the examples herein;
FIG. 7 is a line graph of the effect of various drugs provided in the examples herein on serum parathyroid hormone (PTH) in mice.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present application clearer, the technical solutions of the embodiments of the present application will be clearly and completely described below. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
The embodiment of the application provides application of the medicine in preparing a medicine for treating liver injury and bone injury caused by vitamin A poisoning. The medicine is prepared by adding some auxiliary materials into the medicine, and the auxiliary materials can be, for example: starch, dextrin, calcium carbonate, carboxymethyl cellulose, and the like. The following medicines can effectively treat liver injury and bone injury caused by vitamin A poisoning and relieve adverse reactions caused by vitamin A poisoning.
The herpetospermum pedunculosum seeds are dry mature seeds of herpetospermum pedunculosum of herpetospermum of cucurbitaceae, and are common Tibetan medicines. Has effects of clearing heat of viscera and gallbladder, and can be used for treating dyspepsia.
The herpetospermum pedunculosum seed ether extract can be purchased from the market, and can also be prepared by the following method. The extraction method can be Soxhlet extraction, and comprises placing Herpetospermum caudatum seed powder into a Soxhlet extractor, and adding petroleum ether for extraction. Specifically, 100-200g of herpetospermum pedunculosum seeds powder is weighed, wrapped by filter paper, put into a Soxhlet extractor, added with petroleum ether for Soxhlet extraction for 6-10h, the petroleum ether extract is recovered, and the solvent is evaporated by rotation to dryness to obtain 50-100mL herpetospermum pedunculosum seed ether extract.
The extraction method of the herpetospermum pedunculosum seed ether extract can also be leaching, ultrahigh pressure extraction, supercritical extraction, etc. The extraction solvent can be petroleum ether, diethyl ether, aromatic ether, etc.
Penthorum chinense Pursh, also known as penthorum chinense Pursh, Eupatorium japonicum, and Salix purpurea, refers to the aerial parts of penthorum chinense Pursh of the genus Geranium of the family Saxifragaceae. Penthorum chinense Pursh has effects of clearing heat and detoxicating, eliminating jaundice and dampness, promoting blood circulation and removing blood stasis, and inducing diuresis and detumescence.
The penthorum chinense pursh water extract can be purchased from the market and also can be prepared by the following method. The extraction method can be Soxhlet extraction, and comprises placing herba Penthori chinensis powder into a Soxhlet extractor, and adding distilled water for extraction. Specifically, 100-200g of penthorum chinense pursh powder is weighed, wrapped by filter paper, put into a Soxhlet extractor, added with distilled water for Soxhlet extraction for 6-10h, the extract is recovered, the solvent is evaporated by distillation in a water bath, and redissolved by distilled water to obtain 60-120mL of penthorum chinense pursh water extract.
The penthorum chinense pursh water extract can be extracted by an extraction method, an ultrahigh pressure extraction method, a supercritical extraction method and the like. Astragalus polysaccharides are commercially available.
In the embodiment of the application, the medicine for treating liver injury and bone injury caused by vitamin A poisoning comprises herpetospermum pedunculosum seed ether extract and/or penthorum chinense pursh water extract. Alternatively, the drug for treating liver injury and bone injury due to vitamin A poisoning may be herpetospermum pedunculosum seed ether extract; the medicine for treating liver injury and bone injury due to vitamin A poisoning can be penthorum chinense Pursh water extract; the medicine for treating liver injury and bone injury caused by vitamin A poisoning may also be pedunculate herpetospermum seed ether extract and penthorum chinense pursh water extract.
In order to improve the effect of treating liver injury and bone injury caused by vitamin A poisoning, the medicine for treating liver injury and bone injury caused by vitamin A poisoning can also comprise 4-6 parts by weight of penthorum chinense pursh water extract (such as 4g, 4.5g, 5g, 5.5g or 6g) and 0.5-2 parts by weight of astragalus polysaccharide (such as 0.5g, 1g, 1.5g or 2 g). Mixing them directly.
The medicine for treating liver injury and bone injury due to vitamin A poisoning may further comprise 0.2-1 weight part of herpetospermum pedunculatum seed ether extract (such as 0.2g, 0.4g, 0.6g, 0.8g or 1g) and 0.5-2 weight parts of Astragalus polysaccharides (such as 0.5g, 1g, 1.5g or 2 g). Mixing them directly.
The medicine for treating liver injury and bone injury due to vitamin A poisoning may further comprise 4-6 weight parts of herba Penthori chinensis water extract (such as 4g, 4.5g, 5g, 5.5g or 6g) and 0.2-1 weight part of semen Herpetospermi ether extract (such as 0.2g, 0.4g, 0.6g, 0.8g or 1 g). Mixing them directly.
The medicine for treating liver injury and bone injury due to vitamin A poisoning may further comprise 4-6 weight parts of herba Penthori chinensis water extract (such as 4g, 4.5g, 5g, 5.5g or 6g), 0.2-1 weight parts of herpetospermum pedunculosum seed ether extract (such as 0.2g, 0.4g, 0.6g, 0.8g or 1g), and 0.5-2 weight parts of Astragalus polysaccharides (such as 0.5g, 1g, 1.5g or 2 g). Mixing them directly.
Example 1
1. Materials and methods
1.1 Experimental animals and groups
36 healthy adult Kunming mice with the body mass of 18-22 g and half of the male and the female are purchased to the experimental animal center of Sichuan university Hospital in Huaxi. Raising the seedlings in an environment of 25-28 ℃ for 2-3 days. Vitamin A (1500 mg/kg) is injected into the abdominal cavity at one time to form an acute poisoning model mouse which is used as an experimental animal. The treatment experiment was started four weeks after intoxication.
Animals with bone dysplasia syndrome caused by vitamin A poisoning are randomly divided into six groups of 6 mice each. The first group was control, no treatment, treatment 1; the second group is a penthorum chinense pursh water extract treatment group, and the stomach is continuously drenched for 7 days according to 10mL/kg, and is a treatment group 2; the third group is a herpetospermum pedunculosum seed ether extract treatment group, and the treatment is carried out for 7 days by continuous intragastric administration according to 1 mL/kg; the fourth group is a treatment group of penthorum chinense Pursh water extract and herpetospermum pedunculosum seeds ether extract, and the treatment group is treatment 4 by continuously intragastric administration of 5mL/kg penthorum chinense Pursh water extract and 0.5mL/kg herpetospermum seeds ether extract for 7 d; the fifth group is a treatment group of penthorum chinense Pursh water extract, herpetospermum pedunculosum seed ether extract and astragalus polysaccharide, and the fifth group is a treatment group of penthorum chinense Pursh water extract, herpetospermum pedunculosum seed ether extract and astragalus polysaccharide, wherein the fifth group is a treatment group of 5 which is that 5 is a treatment group of continuously intragastric administration of 5mL/kg penthorum chinense Pursh water extract, 0; the sixth group was positive control, and Angongniuhuang Wan (1/3 pills, 1g) was taken as control, and treatment 6 was given orally.
1.2 extraction and treatment of Chinese herbs
The Chinese medicines of herpetospermum pedunculosum seeds and penthorum chinense pursh, first-grade products, are purchased to the Chinese medicine wholesale market of Chengdu. Astragalus polysaccharides, first grade, purchased in Hua M ü kang veterinary drug mall. Petroleum ether was analytically pure.
Weighing 100g of herpetospermum pedunculosum seeds powder, wrapping with filter paper, putting into a Soxhlet extractor, adding petroleum ether, performing Soxhlet extraction for 6h, recovering the petroleum ether extract, and rotationally evaporating the solvent to dryness to obtain 50mL of herpetospermum pedunculosum seeds ether extract.
Weighing 100g of penthorum chinense pursh powder, wrapping with filter paper, putting into a Soxhlet extractor, adding distilled water, Soxhlet extracting for 6h, recovering the extract, evaporating the solvent in a water bath, and re-dissolving with distilled water to obtain 60mL of penthorum chinense pursh water extract.
1.3 Experimental methods and reagents
The test mice were subjected to measurement of alanine Aminotransferase (ALT), aspartate Aminotransferase (AST), calcium (Ca), alkaline phosphatase (ALP), and Parathyroxine (PTH) by taking venous blood on days 2, 4, 6, and 8 from the start of treatment.
The kit comprises a mouse alanine Aminotransferase (ALT) determination kit, a mouse serum glutamic-oxaloacetic transaminase (AST) determination kit, a mouse serum alkaline phosphatase (ALP) determination kit and a mouse serum Parathyroxine (PTH) determination kit, and is purchased from Wuhan Youlh science and technology, Inc. A mouse serum calcium (Ca) determination kit and a mouse serum phosphorus (P) determination kit are purchased from Nanjing to build a bioengineering institute.
1.4 determination
0.2mL of the separated serum was taken and AST, ALT, Ca, P, ALP, and PTH were measured by the method described in the kit.
1.5 data processing
Statistical analysis was performed using SPSS 22.0 software, and when differences were significant, multiple comparisons were performed using ANOVA procedure, with P <0.01 (very significant difference) and P <0.05 (significant difference) as the criterion for significance of the difference, and data are presented as mean ± standard deviation.
2. Results
2.1 Effect on vitamin A acute poisoning mouse serum alanine Aminotransferase (ALT)
Treatments 2-5 provided example drugs, and the effect of blank treatment 1 and other drug treatment 6 on serum glutamic pyruvic transaminase (ALT) in vitamin a acutely poisoned mice, as in table 1, where the units of data in table 1 are ng/mL, multiple comparisons between columns, different capital letters in shoulder, indicate that the difference is significant, P < 0.01; the lower case letters are different, indicating significant difference, P < 0.05.
TABLE 1 Effect of various drugs on serum glutamate pyruvate transaminase in mice
Figure GDA0002979286110000071
Figure GDA0002979286110000081
The effect of each drug on serum glutamic pyruvic transaminase (ALT) in mice is plotted by a line graph according to the contents of table 1 as shown in fig. 1. As can be seen from Table 1 and FIG. 1, no significant change was observed in serum alanine Aminotransferase (ALT) assay of vitamin A acutely poisoned mice, with 9.77. + -. 0.51ng/mL, 9.66. + -. 0.54ng/mL, 9.98. + -. 0.43ng/mL, and 9.22. + -. 0.61ng/mL on days 2, 4, 6, and 8, respectively. The penthorum chinense pursh water extract treatment group (treatment 2) declines from day 6, and has slight decline in the whole period, and the decline at day 2, day 4, day 6 and day 8 are respectively 9.82 +/-0.27 ng/mL, 10.04 +/-0.30 ng/mL, 8.50 +/-0.18 ng/mL and 7.53 +/-0.19 ng/mL; the total period of the treatment group (treatment 3) of the herpetospermum pedunculosum seed ether extract is obviously reduced, and the total period of the treatment group on day 2, day 4, day 6 and day 8 is respectively 10.05 +/-0.21 ng/mL, 8.92 +/-0.17 ng/mL, 7.99 +/-0.10 ng/mL and 5.50 +/-0.14 ng/mL; the total period of the penthorum chinense pursh water extract and herpetospermum pedunculosum seed ether extract treatment group (treatment 4) is more obviously reduced, and the total period of the penthorum chinense pursh water extract and herpetospermum pedunculosum seed ether extract treatment group (treatment 4) on the 2 nd day, the 4 th day, the 6 th day and the 8 th day is respectively 8.90 +/-0.28 ng/mL, 6.97 +/-0.12 ng/mL, 5.76 +/-0.25 ng/mL and 4.92 +/-0.17 ng/mL; the treatment group (treatment 5) of penthorum chinense pursh water extract, herpetospermum pedunculosum seed ether extract and astragalus polysaccharide has the most obvious reduction in all treatment modes, and the treatment groups on day 2, day 4, day 6 and day 8 are respectively 9.39 +/-0.30 ng/mL, 7.42 +/-0.08 ng/mL, 5.02 +/-0.02 ng/mL and 3.78 +/-0.14 ng/mL; the positive control (treatment 6) also showed significant effects, 11.09. + -. 0.18ng/mL, 7.58. + -. 0.23ng/mL, 5.52. + -. 0.18ng/mL, and 3.87. + -. 0.18ng/mL on day 2, 4, 6, and 8, respectively.
2.2 Effect on serum aspartate Aminotransferase (AST) in mice acutely poisoned by vitamin A
Treatments 2-5 provided example drugs, and the effect of blank treatment 1 and other drug treatment 6 on serum aspartate Aminotransferase (AST) in vitamin a acutely poisoned mice, as shown in table 2, where the data in table 2 are in pg/mL, multiple comparisons of mean values between columns are made, with capital letters in shoulder notes differing and indicating a significant difference, P < 0.01; the lower case letters are different, indicating significant difference, P < 0.05.
TABLE 2 Effect of various drugs on serum glutamic-oxaloacetic transaminase of mice
Figure GDA0002979286110000091
The effect of each drug on serum aspartate Aminotransferase (AST) in mice is plotted according to the contents of Table 2 in a line graph as shown in FIG. 2. As can be seen from Table 2 and FIG. 2, no significant change was observed in serum aspartate Aminotransferase (AST) of mice acutely poisoned with vitamin A in the control group (treatment 1), and on day 2, day 4, day 6 and day 8, the serum AST was 1785.36. + -. 74.57pg/mL, 1789.51. + -. 19.19pg/mL, 1820.26. + -. 70.31pg/mL and 1730.64. + -. 68.30pg/mL, respectively; the total period of the penthorum chinense pursh water extract treatment group (treatment 2) is obviously reduced, and the total period of the treatment groups on the 2 nd day, the 4 th day, the 6 th day and the 8 th day is respectively 1774.45 +/-55.35 pg/mL, 1285.00 +/-77.61 pg/mL, 984.31 +/-24.35 pg/mL and 540.98 +/-50.23 pg/mL; the drop of the whole period of the treatment group (treatment 3) of the herpetospermum pedunculosum seed ether extract is slow, and the total period of the treatment group on day 2, day 4, day 6 and day 8 is 1812.26 +/-55.32 pg/mL, 1652.24 +/-35.85 pg/mL, 1475.15 +/-32.54 pg/mL and 1011.06 +/-22.26 pg/mL respectively; the total period of the penthorum chinense pursh water extract and herpetospermum pedunculosum seed ether extract treatment group (treatment 4) is obviously reduced, and the total period of the penthorum chinense pursh water extract and herpetospermum pedunculosum seed ether extract treatment group is 1565.39 +/-60.48 pg/mL, 1336.34 +/-28.40 pg/mL, 1080.39 +/-65.13 pg/mL and 665.80 +/-36.74 pg/mL respectively on day 2, day 4, day 6 and day 8; the treatment group (treatment 5) of penthorum chinense pursh water extract, herpetospermum pedunculosum seed ether extract and astragalus polysaccharide has obvious reduction in all treatment modes, and the treatment groups on the 2 nd day, the 4 th day, the 6 th day and the 8 th day are 1795.05 +/-49.31 pg/mL, 1277.92 +/-26.30 pg/mL, 948.50 +/-36.12 pg/mL and 628.14 +/-26.68 pg/mL respectively; the positive control group (treatment 6) showed a more general effect, with 1835.32. + -. 10.73pg/mL, 1733.87. + -. 54.65pg/mL, 1633.18. + -. 50.40pg/mL, and 1233.81. + -. 36.45pg/mL on day 2, 4, 6, and 8, respectively.
Alanine Aminotransferase (ALT) and aspartate Aminotransferase (AST) are two important biochemical indicators that measure liver function in animals. Of these, ALT is mainly present in the liver cell plasma, and AST is mainly distributed in the liver cell plasma and mitochondria of liver cells. When normal, only a small amount of the blood is released into the blood; when the liver cells die, ALT and AST are released into blood in large quantities, and the concentration in serum is increased to the same extent as that of the damaged liver cells. In liver function examination, ALT is an index reflecting damage of hepatocytes, and AST is a standard reflecting necrosis of hepatocytes.
2.1 and 2.2, the effect of the crude oil extracted from herpetospermum pedunculosum seeds on reducing ALT (ALT) rise caused by acute poisoning of vitamin A is slightly better than that of the crude extract extracted from penthorum chinense pursh water, the effect of the combined action of the two is further improved and is better than that of a single action group, and the effect is further improved by adding astragalus polysaccharide and is slightly better than that of the bezoar chest functioning pill. The optimum was achieved in all the treatment protocols tested. This is probably due to the effect of astragalus polysaccharides in stimulating autoimmunity. For AST, the penthorum chinense pursh water crude extract has the best effect of reducing AST increase caused by vitamin A acute poisoning, and is superior to the crude oil extraction of herpetospermum pedunculosum seeds, and is slightly superior to the mixture of the penthorum pedunculosum and the sunflower seeds. Is superior to the curative effect of Angongniuhuang pills. In general, the penthorum chinense pursh water crude extract, the crude oil of the herpetospermum pedunculosum seeds and the astragalus polysaccharide have the best effect of treating liver injury caused by acute poisoning of vitamin A, can repair the liver injury and accelerate the metabolism of necrotic liver cells, thereby achieving the purpose of correcting the liver function, and the effect is greatly superior to that of the Angong bezoar pill of a control group.
2.3 Effect on serum calcium (Ca) of vitamin A acutely poisoned mice
Treatments 2-5 provided example drugs, and the effect of blank treatment 1 and other drug treatment 6 on serum calcium (Ca) in vitamin a acutely poisoned mice, as shown in table 3, where the data in table 3 is in mol/L, multiple comparisons of mean values between columns are made, with capital letters in shoulder notes being different, indicating that the difference is significant, P < 0.01; the lower case letters are different, indicating significant difference, P < 0.05.
TABLE 3 Effect of various drugs on serum calcium in mice
Figure GDA0002979286110000101
Figure GDA0002979286110000111
The effect of each drug on serum calcium (Ca) in mice is plotted according to the contents of table 3 in a line graph as shown in fig. 3. As can be seen from Table 3 and FIG. 3, no significant change was observed in serum Ca of the control group (treatment 1) as measured by serum calcium (Ca) of mice acutely poisoned with vitamin A, and the concentration of Ca was 9.94. + -. 0.93mmol/L, 9.57. + -. 0.37mmol/L, 9.35. + -. 0.24mmol/L and 9.40. + -. 0.33mmol/L on day 2, 4, 6 and 8, respectively; the penthorum chinense pursh water extract treatment group (treatment 2) has a relatively obvious decline, and the weight of the penthorum chinense pursh water extract treatment group on the 2 nd day, the 4 th day, the 6 th day and the 8 th day are respectively 9.98 +/-0.44 mmol/L, 7.70 +/-0.24 mmol/L, 7.33 +/-0.34 mmol/L and 6.45 +/-0.21 mmol/L; the trend of the herpetospermum pedunculosum seed ether extract treatment group (treatment 3) is similar to that of the penthorum chinense pursh water extract treatment group, and the trend of the herpetospermum pedunculosum seed ether extract treatment group on the 2 nd day, the 4 th day, the 6 th day and the 8 th day is respectively 10.77 +/-0.38 mmol/L, 7.54 +/-0.29 mmol/L, 6.52 +/-0.28 mmol/L and 5.81 +/-0.16 mmol/L; the whole period of the penthorum chinense pursh water extract and herpetospermum pedunculosum seed ether extract treatment group (treatment 4) is obviously reduced, the total amount of the penthorum chinense pursh water extract and herpetospermum pedunculosum seed ether extract treatment group is respectively 7.42 +/-0.32 mmol/L, 6.42 +/-0.61 mmol/L, 3.80 +/-0.25 mmol/L and 2.61 +/-0.25 mmol/L on the days 2, 4, 6 and 8, and the total amount of the penthorum chinense pursh water extract and herpetospermum peduncu; the treatment group (treatment 5) of the penthorum chinense pursh water extract, the herpetospermum pedunculosum seed ether extract and the astragalus polysaccharide is also reduced obviously, the trend is similar to that of the treatment group of the penthorum chinense pursh water extract, the herpetospermum pedunculosum seed ether extract, and the trend is respectively 7.99 +/-0.44 mmol/L, 7.15 +/-0.34 mmol/L, 3.84 +/-0.30 mmol/L and 3.29 +/-0.40 mmol/L on the 2 nd day, the 4 th day, the 6 th day and the 8 th day; the positive control group (treatment 6) showed no significant change, and the concentrations on day 2, 4, 6 and 8 were 10.80. + -. 0.50mmol/L, 9.93. + -. 0.30mmol/L, 9.75. + -. 0.12mmol/L and 9.37. + -. 0.39mmol/L, respectively.
2.4 Effect on serum phosphorus (P) in vitamin A acutely poisoned mice
Treatments 2-5 provided example drugs, and the effect of blank treatment 1 and other drug treatment 6 on serum phosphorus (P) in vitamin a acutely poisoned mice, as shown in table 4, where the data in table 4 is in mol/L, multiple comparisons of mean values between columns are made, with capital letters in shoulder notes being very significant, P < 0.01; the lower case letters are different, indicating significant difference, P < 0.05.
TABLE 4 Effect of various drugs on serum phosphorus in mice
Figure GDA0002979286110000121
The effect of each drug on serum phosphorus (P) in mice is plotted according to the contents of table 4 in a line graph as shown in fig. 4. As can be seen from Table 4 and FIG. 4, no significant change was observed in serum P of the control group (treatment 1) as measured by serum phosphorus (P) of vitamin A acutely poisoned mice, and the serum P was found to be 2.92. + -. 0.32mmol/L, 2.72. + -. 0.27mmol/L, 2.71. + -. 0.22mmol/L and 2.99. + -. 0.22mmol/L on day 2, 4, 6 and 8, respectively; the penthorum chinense pursh water extract treatment group (treatment 2) has a relatively obvious decline, and the treatment days 2, 4, 6 and 8 are respectively 3.14 +/-0.13 mmol/L, 3.20 +/-0.20 mmol/L, 2.72 +/-0.10 mmol/L and 2.35 +/-0.11 mmol/L; the trend of the herpetospermum pedunculosum seed ether extract treatment group (treatment 3) is similar to that of the penthorum chinense pursh water extract treatment group, and the trend of the herpetospermum pedunculosum seed ether extract treatment group on the 2 nd day, the 4 th day, the 6 th day and the 8 th day is respectively 3.04 +/-0.21 mmol/L, 3.12 +/-0.07 mmol/L, 2.37 +/-0.08 mmol/L and 2.00 +/-0.11 mmol/L; the total period of the penthorum chinense pursh water extract and herpetospermum pedunculosum seed ether extract treatment group (treatment 4) is obviously reduced, and the total period of the treatment group on the 2 nd day, the 4 th day, the 6 th day and the 8 th day is respectively 3.29 +/-0.28 mmol/L, 3.07 +/-0.07 mmol/L, 2.34 +/-0.09 mmol/L and 1.61 +/-0.12 mmol/L; the treatment group (treatment 5) of penthorum chinense Pursh water extract, herpetospermum pedunculosum seed ether extract and astragalus polysaccharide is also reduced obviously, the trend is similar to that of the treatment group of penthorum chinense Pursh water extract, herpetospermum pedunculosum seed ether extract, and the trend is respectively 3.31 +/-0.15 mmol/L, 3.07 +/-0.07 mmol/L, 2.32 +/-0.04 mmol/L and 1.62 +/-0.11 mmol/L on the 2 nd day, the 4 th day, the 6 th day and the 8 th day; the positive control group (treatment 6) showed no significant change, and the concentrations on day 2, 4, 6 and 8 were 3.06. + -. 0.21mmol/L, 3.06. + -. 0.30mmol/L, 3.05. + -. 0.06mmol/L and 2.97. + -. 0.19mmol/L, respectively.
Calcium, phosphorus, is an important constituent element constituting animal bone tissue, about 80% of phosphorus, and more than 99% of calcium is stored in bone in the form of calcium phosphate. The increase and decrease of the free serum calcium and phosphorus concentration reflects the abnormal change of the animal bone tissue to some extent. The inventor finds out in research that: when the bone symptoms appear in the mouse, the serum calcium is greatly increased, and the serum phosphorus is slightly increased, so that the calcium-phosphorus ratio in the serum is greatly increased.
From the contents of 2.3 and 2.4, the herpetospermum pedunculosum seed ether extract and the penthorum chinense water extract can greatly reduce the serum calcium and phosphorus concentrations of mice caused by acute poisoning of vitamin A, and the combination of the herpetospermum pedunculosum seed ether extract and the penthorum chinense water extract has better effect and larger reduction amplitude. The bezoar chest functioning pill of the control group does not have the efficacy, but has poor efficacy for reducing the concentration of calcium and phosphorus in the blood serum of mice caused by acute poisoning of vitamin A.
FIG. 5 shows the effect of various drugs on the serum calcium-phosphorus ratio of mice acutely poisoned by vitamin A. from FIG. 5, it can be seen that when the drug therapy is used to reduce the bone symptoms of mice caused by acute poisoning by vitamin A, the pedunculate herpetospermum seed ether extract and the penthorum chinense pursh water extract cause the increase of the serum calcium-phosphorus ratio, and after the two are combined, the serum calcium-phosphorus ratio is further increased. This is probably because animals need a large amount of calcium and phosphorus elements to reconstruct bone tissue when repairing damaged bone tissue, and only a large amount of calcium is released from blood when damaged, so that more phosphorus needs to be taken in to supplement in order to achieve balance when repairing bone tissue, thereby resulting in an increase in the calcium-phosphorus ratio in serum.
2.5 Effect on acute toxicity of vitamin A on serum alkaline phosphatase (ALP) in mice
Treatments 2-5 provided example drugs, and the effect of blank treatment 1 and other drug treatment 6 on serum alkaline phosphatase (ALP) in vitamin a acutely poisoned mice, as in table 5, where the data in table 5 is in ng/mL, multiple comparisons of mean values between columns are made, with capital letters in shoulder boxes being different, indicating that the difference is significant, P < 0.01; the lower case letters are different, indicating significant difference, P < 0.05.
TABLE 5 Effect of various drugs on serum alkaline phosphatase in mice
Figure GDA0002979286110000131
Figure GDA0002979286110000141
The effect of each drug on mouse serum alkaline phosphatase (ALP) is plotted according to the contents of Table 5 as shown in FIG. 6. As can be seen from Table 5 and FIG. 6, no significant change was observed in serum alkaline phosphatase (ALP) in mice acutely poisoned with vitamin A, and the serum ALP of the control group (treatment 1) was found to be 7.62. + -. 0.35ng/mL, 7.18. + -. 0.20ng/mL, 6.94. + -. 0.31ng/mL, and 7.70. + -. 0.40ng/mL on days 2, 4, 6, and 8, respectively; the penthorum chinense pursh water extract treatment group (treatment 2) has obvious reduction in the whole period, and the total reduction is respectively 7.73 +/-0.54 ng/mL, 6.00 +/-0.16 ng/mL, 3.85 +/-0.24 ng/mL and 2.08 +/-0.12 ng/mL on the days 2, 4, 6 and 8; the treatment group (treatment 3) with the herpetospermum pedunculosum seed ether extract also has a remarkable decrease, and the treatment groups are slow compared with other treatment groups, and the treatment groups are respectively 8.67 plus or minus 0.30ng/mL, 7.07 plus or minus 0.25ng/mL, 5.67 plus or minus 0.11ng/mL and 4.51 plus or minus 0.29ng/mL on the 2 nd day, the 4 th day, the 6 th day and the 8 th day; the treatment group (treatment 4) of the penthorum chinense pursh water extract and the herpetospermum pedunculosum seed ether extract has obvious reduction in the whole period, the speed is similar to that of the treatment group (treatment 2) and the treatment group (treatment 5), and the treatment speed is respectively 8.46 +/-0.39 ng/mL, 5.47 +/-0.30 ng/mL, 3.43 +/-0.19 ng/mL and 2.04ng/mL on the days 2, 4, 6 and 8; the decline of the treatment group (treatment 5) of the penthorum chinense pursh water extract, the herpetospermum pedunculosum seed ether extract and the astragalus polysaccharide is also obvious, and the treatment groups on the 2 nd day, the 4 th day, the 6 th day and the 8 th day are respectively 9.08 +/-0.34 ng/mL, 5.47 +/-0.43 ng/mL, 3.16 +/-0.14 ng/mL and 2.35 +/-0.40 ng/mL; the positive control group (treatment 6) also showed a slightly lower effect than treatment 2, treatment 4 and treatment 5, and the results on days 2, 4, 6 and 8 were 8.61. + -. 0.38ng/mL, 7.00. + -. 0.21ng/mL, 5.92. + -. 0.36ng/mL and 2.93. + -. 0.43ng/mL, respectively.
Alkaline phosphatase (ALP) is an enzyme that is widely distributed in animal liver, bone, intestine, kidney, placenta, etc. tissues and is excreted outside the gallbladder through the liver. This enzyme catalyzes the removal of the 5 ' phosphate group from the nucleic acid molecule, thereby converting the 5 ' -P terminus of the DNA or RNA fragment to a 5 ' -OH terminus. It is not a single enzyme, but a group of isoenzymes. Six isozymes, ALP1, ALP2, ALP3, ALP4, ALP5 and ALP6, have been found. Of these, species 1, 2, and 6 are derived from the liver, species 3 from bone cells, species 4 from placenta and cancer cells, and species 5 from small intestine villous epithelium and fibroblasts. Clinically, ALP is mainly used for diagnosis and differential diagnosis of diseases of skeleton, liver and gall system, and the pathological rise particularly reflects the condition of bone injury caused by liver injury.
From the content of 2.5, the effect of the penthorum chinense pursh water extract on reducing the serum ALP of mice caused by acute poisoning of vitamin A is better than that of the herpetospermum pedunculosum seed ether extract, and when the penthorum chinense pursh water extract and the herpetospermum pedunculosum seed ether extract are used together, the effect of reducing the serum ALP is similar to that of the penthorum chinense pursh water extract and is better than.
2.6 Effect on serum parathyroid hormone (PTH) in mice acutely poisoned by vitamin A
Treatments 2-5 provided example drugs, and the effect of blank treatment 1 and other drug treatment 6 on serum parathyroid hormone (PTH) in vitamin a acutely poisoned mice, as in table 6, where the data in table 6 are in pg/mL, multiple comparisons of mean values between columns are made, with capital letters in shoulder notes being different, indicating that the difference is significant, P < 0.01; the lower case letters are different, indicating significant difference, P < 0.05.
TABLE 6 Effect of various drugs on serum parathyroid hormone in mice
Figure GDA0002979286110000151
The effect of each drug on serum parathyroid hormone (PTH) in mice is plotted according to the contents of table 6 as a line graph as shown in figure 7. As can be seen from Table 6 and FIG. 7, no significant change was observed in serum PTH of the control group (treatment 1) as determined by serum parathyroid hormone (PTH) of mice acutely poisoned with vitamin A, and on days 2, 4, 6 and 8, 102.24. + -.6.57 pg/mL, 116.16. + -.2.90 pg/mL, 96.06. + -.4.97 pg/mL and 92.13. + -.4.20 pg/mL, respectively; the total phase of the penthorum chinense pursh water extract treatment group (treatment 2) is obviously increased, and the total phase of the penthorum chinense pursh water extract treatment group on the 2 nd day, the 4 th day, the 6 th day and the 8 th day is respectively 125.44 +/-8.59 pg/mL, 172.25 +/-13.66 pg/mL, 238.74 +/-20.86 pg/mL and 290.78 +/-12.42 pg/mL; the treatment group (treatment 3) of the herpetospermum pedunculosum seed ether extract also has obvious increase, the trend is similar to that of the treatment 2, and the treatment groups on the 2 nd, the 4 th, the 6 th and the 8 th days are respectively 121.16 +/-8.20 pg/mL, 170.46 +/-2.67 pg/mL, 319.10 +/-17.46 pg/mL and 332.66 +/-7.17 pg/mL; the total period of the penthorum chinense pursh water extract and herpetospermum pedunculosum seed ether extract treatment group (treatment 4) is increased rapidly, and the total period of the penthorum chinense pursh water extract and herpetospermum pedunculosum seed ether extract treatment group (treatment 4) is 182.60 +/-5.12 pg/mL, 265.92 +/-9.00 pg/mL, 319.10 +/-17.46 pg/mL and 332.66 +/-7.17 pg/mL respectively on day 2, day 4, day 6 and day 8; the increase of the treatment group (treatment 5) of penthorum chinense pursh water extract, herpetospermum pedunculosum seed ether extract and astragalus polysaccharide is also obvious, the trend is similar to that of the treatment 4, and the treatment groups on the 2 nd day, the 4 th day, the 6 th day and the 8 th day are 192.41 +/-8.02 pg/mL, 270.98 +/-11.34 pg/mL, 308.99 +/-3.46 pg/mL and 337.95 +/-6.05 pg/mL respectively; the positive control (treatment 6) showed a slight increase in efficacy, 92.67. + -. 3.6pg/mL, 108.43. + -. 9.10pg/mL, 119.61. + -. 2.81pg/mL, 136.68. + -. 2.45pg/mL on day 2, 4, 6 and 8, respectively.
Parathyroxine (PTH) is a linear polypeptide containing 84 amino acid residues, with a molecular weight of 9500, whose biological activity depends on amino acid residues 1-27 of the amino terminus. PTH is the major hormone in the body that maintains blood calcium homeostasis, and the overall effect is to raise blood calcium and lower blood phosphorus levels, reflecting changes in serum calcium-phosphorus ratio.
From the contents of 2.6, it can be seen that the penthorum chinense pursh water extract and the pedunculate herpetospermum seed ether extract cause a significant increase in PTH due to their efficacy in repairing bone injury in mice caused by acute poisoning with vitamin a. The combined action of the two components has stronger effect of repairing bone injury, so that the PTH is further increased. The Angong Niuhuang Wan has no effect of repairing bone injury, so the concentration of PTH is not changed greatly.
To sum up: in the medicine provided by the embodiment of the application, the penthorum chinense pursh water extract and the herpetospermum pedunculosum seed ether extract have the effect of treating the bone injury of mice caused by acute poisoning of vitamin A, and the penthorum chinense pursh water extract and the herpetospermum pedunculosum seed ether extract are used together to achieve a better effect. In particular to a medicine treatment combination of penthorum chinense pursh water extract, herpetospermum pedunculosum seed ether extract and astragalus polysaccharide, which has the best curative effect. Is superior to traditional Chinese medicine bezoar chest functioning pill.
The embodiments described above are some, but not all embodiments of the present application. The detailed description of the embodiments of the present application is not intended to limit the scope of the claimed application, but is merely representative of selected embodiments of the application. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present application.

Claims (8)

1. The application of a medicine in preparing a medicine for treating liver injury and bone injury caused by vitamin A poisoning is characterized in that the medicine is an extract of herpetospermum pedunculosum seed ether.
2. The application of a medicine in preparing a medicine for treating liver injury and bone injury caused by vitamin A poisoning is characterized in that the medicine is a penthorum chinense pursh water extract.
3. The application of a medicine in preparing a medicine for treating liver injury and bone injury caused by vitamin A poisoning is characterized in that the medicine consists of herpetospermum pedunculosum seed ether extract and penthorum chinense pursh water extract.
4. The use of the medicament according to claim 3 for the preparation of a medicament for the treatment of liver and bone damage caused by vitamin A poisoning, wherein the medicament consists of 4-6 parts by weight of the aqueous extract of penthorum chinense pursh and 0.2-1 part by weight of the ether extract of pedunculate herpetospermum seeds.
5. The application of a medicine in preparing a medicine for treating liver injury and bone injury caused by vitamin A poisoning is characterized in that the medicine consists of penthorum chinense pursh water extract, herpetospermum pedunculosum seed ether extract and astragalus polysaccharide.
6. The use of the medicament according to claim 5 in the preparation of a medicament for the treatment of liver and bone damage due to vitamin A poisoning, wherein the medicament is composed of 4-6 parts by weight of a water extract of penthorum chinense Pursh, 0.2-1 part by weight of an ether extract of herpetospermum pedunculosum seeds, and 0.5-2 parts by weight of astragalus polysaccharides.
7. A medicine for treating liver injury and bone injury caused by vitamin A poisoning is characterized by comprising 4-6 parts by weight of penthorum chinense pursh water extract and 0.2-1 part by weight of herpetospermum pedunculosum seed ether extract.
8. A medicine for treating liver injury and bone injury caused by vitamin A poisoning is characterized by comprising 4-6 parts by weight of penthorum chinense pursh water extract, 0.2-1 part by weight of herpetospermum pedunculosum seed ether extract and 0.5-2 parts by weight of astragalus polysaccharide.
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