CN103224572A - Preparation of alginic acid cerium complex and application of alginic acid cerium as antiemetic drugs - Google Patents
Preparation of alginic acid cerium complex and application of alginic acid cerium as antiemetic drugs Download PDFInfo
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- CN103224572A CN103224572A CN2012100213668A CN201210021366A CN103224572A CN 103224572 A CN103224572 A CN 103224572A CN 2012100213668 A CN2012100213668 A CN 2012100213668A CN 201210021366 A CN201210021366 A CN 201210021366A CN 103224572 A CN103224572 A CN 103224572A
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- alginic acid
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Abstract
The invention relates to an alginic acid cerium complex, a preparation method and an application of the alginic acid cerium complex in preparation of antiemetic drugs, the alginic acid cerium complex is prepared by cerous sulfate and sodium alginate with low molecular weight, and has good curative effect to emesis.
Description
Technical field
The present invention relates to the preparation of alginic acid cerium complexes and as the purposes of the medicine of emesis.
Background technology
Vomiting is human misery reaction unbearably.Improper diet, nervous, gastrointestinal tract disease, carcinosis radiotherapy and chemotherapy, drug toxicity, postoperative, cinetosis and gestation etc. can cause nausea and vomiting and all can cause vomiting, frequently and tempestuously vomiting can cause malnutrition, complication such as dehydration, electrolyte disturbance, the particularly vomiting that causes of carcinosis radiotherapy and chemotherapy is one of patient's abandoning cure reason.
At present, clinical antiemetic commonly used mainly contains histamine, vagusstoff, Dopamine Receptors antagonistic, bradykinin (NK
1) and serotonin (5-HT
3) short of money dose of acceptor etc., but the weak curative effect that these medicines are vomitted after to chemotherapy, and toxic side effect is strong, is very limited in the application.Novel antiemetic is as NK
1And 5-HT
3Receptor antagonist though antiemetic effect is good, costs an arm and a leg, and use range is narrow, and the toxic side effects of maincenter and periphery is big, the clinical drug combinations that need, the initiative of therefore demanding novel anti vomiting medicine urgently more.
Cerium (Cerium) is to be present in natural rare earth element, and its abundance in the earth's crust and ocean is suitable with metallic zinc, extensively is present in biological and the human body.Ce elements receives publicity day by day in the application of medical treatment with bioengineering field.Biological activitys such as cerium compound has anti-inflammatory, anti-tells, antibiotic, but, limited its application because of toxicity is bigger.Alginic acid is the natural polysaccharide that comes from the ocean, can be used as foodstuff additive and protective foods, and human body is had provide protection.The present invention makes the alginic acid cerium complexes with alginic acid and cerous sulfate, and proved that at novel mink vomiting model (see us relevant patent ZL200810104556.X and ZL201110049334.4) it has better curative effect and toxicity little to vomiting, has finished the present invention thus.
Summary of the invention
Its purposes in the medicine of preparation minimizing vomiting of preparation method that the purpose of this invention is to provide a kind of alginic acid cerium complexes.
The preparation preparation method of alginic acid cerium complexes is:
Get a certain amount of cerous sulfate and be dissolved in 25ml 20mmolL
-1The damping fluid of HEPES in, slowly add 5mg/ml low-molecular-weight algal acid sodium, occur until small amount of precipitate, regulate PH with NaOH and be 7, centrifugal, separation of supernatant, promptly get the underpressure distillation of water miscible alginic acid cerium complexes, get pale yellow powder, promptly get the alginic acid cerium complexes.
The present invention also comprises the purposes of alginic acid cerium complexes in preparation minimizing vomiting reaction medicine.
The instructions of taking of pharmaceutical composition of the present invention: treatment available capsule of vomiting or tablet, 600mg divides three times one after each meal for each person every day.
The beneficial effect of pharmaceutical composition of the present invention aspect emesis is as follows:
1, pharmaceutical composition of the present invention has good antiemetic effect, has now finished clinical preceding pharmaceutical research at mink vomiting model.Adopt novel mink vomiting model, observe this pharmaceutical composition cis-platinum is caused the antagonistic action over a period to come of mink vomiting model.Studies show that: this alginic acid cerium complexes all has tangible antagonistic action for the vomiting reaction of mink due to cis-platinum, copper sulfate and the Apomorphine, and its effect matches in excellence or beauty with the Western medicine ondansetron.
2, finished in the research of the acute toxicology of mouse, studies show that: this alginic acid cerium complexes does not have influence to feed and behavioral activity etc., and internal organs and pathological observation be no abnormality seen also.Illustrate that this alginic acid cerium complexes toxicity is very little.
Embodiment
Further set forth the preparation of this alginic acid cerium complexes below by embodiment and test example, with and the beneficial effect used at emesis.
Embodiment
The first step: the preparation of alginic acid cerium complexes
Get a certain amount of cerous sulfate and be dissolved in 25ml 20mmolL
-1The damping fluid of HEPES in, slowly add 5mg/ml low-molecular-weight algal acid sodium, occur until small amount of precipitate, regulate PH with NaOH and be 7, centrifugal, separation of supernatant, promptly get the underpressure distillation of water miscible alginic acid cerium complexes, get pale yellow powder, promptly get the alginic acid cerium complexes.
Second step: the preparation of preparation
(1) preparation of medicament composition capsule preparation of the present invention
Get the alginic acid cerium complexes 100mg of above-mentioned steps preparation, take by weighing starch 395mg, Magnesium Stearate 5mg simultaneously, uniform mixing, filled capsules is made the capsule of each pure heavy 500mg.
(2) preparation of pharmaceutical composition tablet of the present invention
Get the alginic acid cerium complexes 100mg of above-mentioned steps preparation, take by weighing starch 295mg, lactose 100mg simultaneously, uniform mixing, with wet granulation, drying, mix with the 5mg Magnesium Stearate whole grain back, and compressing tablet is made the tablet of every pure heavy 500mg.
Test example 1: the pharmacodynamic study of alginic acid cerium complexes treatment vomiting effect
1, test materials
(1) cis-platinum (cisplatin), Shandong Qilu Pharmaceutical Factory produces, lot number: 903005CE, 20mg/ props up.
(2) ondansetron hydrochloride injection liquid, the pharmacy of Olympic Competition health, lot number: 090102,2ml: 4mg.
(3) healthy adult mink, body weight 1.3-1.8kg, male, provide by special cultivation animal rearing center, Qingdao, every animal places the iron cage of 75cm * 50cm * 50cm separately, 24h natural light irradiation, ad lib drinking-water before the experiment.
2, test method:
Mink is divided into 3 groups at random, and 6 every group, the A group is the cis-platinum model control group, and the B group is ondansetron positive drug group, and the C group is alginic acid cerium complexes group.The A group gives the physiological saline pre-treatment; The B group gives ondansetron 7.5m gkg
-1Pre-treatment; The C group gives alginic acid cerium complexes 10mgkg
-1The ig pre-treatment; Each group all gives cis-platinum 7.5mgkg at administration 30min
-1Ip.For observing mink vomiting reaction in the 6h after administration, write down its vomiting latent period, retch and vomiting number of times.
3, experimental result
Compare with control group, alginic acid cerium complexes and ondansetron group all can obviously alleviate retch and vomiting number of times and prolong vomits latent period (P＜0.01).The cerous sulfate group is little to the vomiting influence that cis-platinum causes; And causing the rate of vomitting, alginic acid cerium complexes group of the present invention is lower than the ondansetron group.The results are shown in Table 1.
(7.5mg/kg ip) causes the influence of vomitting and acting on to table 1 alginic acid cerium complexes to cis-platinum
Annotate: compare with control group
cP＜0.01
Test example 2: the pharmacodynamic study of alginic acid cerium complexes to vomitting due to the copper sulfate
1, test materials
(1) copper sulfate, Tianjin recovery fine chemistry industry institute
(2) ondansetron hydrochloride injection liquid, the pharmacy of Olympic Competition health
(3) healthy adult mink, body weight 1.3-1.8kg, male, provide by special cultivation animal rearing center, Qingdao, every animal places the iron cage of 75cm * 50cm * 50cm separately, 24h natural light irradiation, ad lib drinking-water before the experiment.
2, test method:
Mink is divided into 3 groups at random, and 6 every group, the A group is the copper sulfate model control group, and the B group is ondansetron positive drug group, and the C group is alginic acid cerium complexes group.The A group gives the physiological saline pre-treatment; The B group gives ondansetron 7.5mgkg
-1Pre-treatment; The C group gives alginic acid cerium complexes 10mgkg
-1The ig pre-treatment; Each group is all pressed 40mgkg at administration 30min
-1Irritate stomach and give copper sulfate.For observing mink vomiting reaction in the 2h after administration, write down its vomiting latent period, retch and vomiting number of times.
3, experimental result
Compare with control group, alginic acid cerium complexes and ondansetron group all can obviously alleviate retch and vomiting number of times and prolong vomits latent period (P＜0.01).The cerous sulfate group is little to the vomiting influence that cis-platinum causes; And causing the rate of vomitting, alginic acid cerium complexes group of the present invention is lower than the ondansetron group.The results are shown in Table 2.
Table 2 alginic acid cerium complexes causes the influence of the effect of vomitting to copper sulfate (40mg/kg)
Annotate: compare with control group
cP＜0.01
Test example 3: the pharmacodynamic study of alginic acid cerium complexes to vomitting due to the Apomorphine
1, test materials
(1) Apomorphine, sigma company
(2) ondansetron hydrochloride injection liquid, the pharmacy of Olympic Competition health
(3) healthy adult mink, body weight 1.3-1.8kg, male, provide by special cultivation animal rearing center, Qingdao, every animal places the iron cage of 75cm * 50cm * 50cm separately, 24h natural light irradiation, ad lib drinking-water before the experiment.
2, test method:
Mink is divided into 3 groups at random, and 6 every group, the A group is the Apomorphine model control group, and the B group is ondansetron positive drug group, and the C group is alginic acid cerium complexes group.The A group gives the physiological saline pre-treatment; The B group gives ondansetron 7.5mgkg
-1Pre-treatment; The C group gives alginic acid cerium complexes 10mgkg
-1The ig pre-treatment; Each group all gives Apomorphine 0.25mgkg at administration 30min
-1Ip.For observing mink vomiting reaction in the 2h after administration, write down its vomiting latent period, retch and vomiting number of times.
3, experimental result
Compare with control group, alginic acid cerium complexes and ondansetron group all can alleviate retch and vomiting number of times and prolong vomits latent period (P＜0.01).The cerous sulfate group is little to the vomiting influence that cis-platinum causes; And causing the rate of vomitting, alginic acid cerium complexes group of the present invention is lower than the ondansetron group.The results are shown in Table 3.
Table 3 alginic acid cerium complexes is to Apomorphine (0.25mgkg
-1, ip) cause the influence of vomitting and acting on
Annotate: compare with control group
cP＜0.01
Test example 4: the acute toxicity test of pharmaceutical composition of the present invention
1, experimental animal:
Kunming mouse, body weight 20 ± 2g is provided by Qingdao City medicine inspecting institute Experimental Animal Center
2, medicine:
Pharmaceutical composition of the present invention, tragakanta
3, test method:
Alginic acid cerium complexes of the present invention is carried out acute toxicity test.Carry out the maximum dosage-feeding experiment.Get 30 of Kunming mouses, female half and half, ig gives capsule Chinese traditional medicine 1g/mL, every 0.8mL, and it is long-pending that promptly the maximum of mouse is irritated body of stomach, observes mouse active state, diet, ight soil, breathing, body weight and death condition after the medication, observes 14d. continuously
4, test-results:
Each organizes well-grown after the mouse stomach administration, weight increase, and behavior is normal, there is no death and significant reaction.Behind sacrifice of animal, the no abnormal phenomenon of each main organs of visual inspection.
The result shows that brown alga cerium complexes maximal dose oral application of the present invention does not have obvious damage to animal, does not find the toxic reaction to the body generation, is the reliable antiemetic of a kind of new type of safe.
Claims (3)
1. preparation that reduces the alginic acid cerium complexes of vomiting reaction, its preparation method is:
Get a certain amount of cerous sulfate and be dissolved in 25ml 20mmolL
-1The damping fluid of HEPES in, slowly add 5mgml
-1Low-molecular-weight algal acid sodium occurs until small amount of precipitate, regulates PH with NaOH and is 7, and centrifugal, separation of supernatant promptly gets the underpressure distillation of water miscible alginic acid cerium complexes, gets pale yellow powder, promptly gets the alginic acid cerium complexes.
2. the preparation method of alginic acid cerium complexes as claimed in claim 1, also comprise: the product that makes is further made the capsule that contains natural drug composition 100mg or 200mg specification by the pharmacy means of routine, maybe will make the tablet that contains natural drug composition 100mg or 200mg specification by wet granulation technology.
3. as the purposes of each described alginic acid cerium complexes of claim 1-2 in the medicine of preparation minimizing vomiting reaction.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106243240A (en) * | 2016-07-29 | 2016-12-21 | 东南大学 | A kind of method utilizing rare earth ion coordination to prepare natural macromolecular material |
| CN106890268A (en) * | 2017-03-09 | 2017-06-27 | 安徽天康(集团)股份有限公司 | It is a kind of to treat composition of leukaemia and preparation method thereof |
| CN112972473A (en) * | 2021-01-26 | 2021-06-18 | 黑龙江中医药大学 | Medicine for treating adverse reactions of digestive tracts in radiotherapy and chemotherapy of tumors and preparation method thereof |
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| CN101151021A (en) * | 2005-03-28 | 2008-03-26 | 奥瑞克索股份公司 | New pharmaceutical compositions useful in the treatment of pain |
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2012
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Patent Citations (2)
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|---|---|---|---|---|
| CN101151021A (en) * | 2005-03-28 | 2008-03-26 | 奥瑞克索股份公司 | New pharmaceutical compositions useful in the treatment of pain |
| CN101361754A (en) * | 2007-08-09 | 2009-02-11 | 李凌松 | Use of rare-earth element salt or pharmaceutical composition thereof in preparing medicine for treating or preventing diabetes and adiposis |
Non-Patent Citations (2)
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| 汪东风等: "褐藻多糖铈配合物对质粒DNA及牛血清白蛋白的裂解作用", 《中国稀土学报》, vol. 20, no. 3, 30 June 2002 (2002-06-30), pages 283 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106243240A (en) * | 2016-07-29 | 2016-12-21 | 东南大学 | A kind of method utilizing rare earth ion coordination to prepare natural macromolecular material |
| CN106890268A (en) * | 2017-03-09 | 2017-06-27 | 安徽天康(集团)股份有限公司 | It is a kind of to treat composition of leukaemia and preparation method thereof |
| CN106890268B (en) * | 2017-03-09 | 2018-03-16 | 安徽天康(集团)股份有限公司 | A kind of composition for treating leukaemia and preparation method thereof |
| CN112972473A (en) * | 2021-01-26 | 2021-06-18 | 黑龙江中医药大学 | Medicine for treating adverse reactions of digestive tracts in radiotherapy and chemotherapy of tumors and preparation method thereof |
| CN112972473B (en) * | 2021-01-26 | 2021-11-02 | 黑龙江中医药大学 | Medicine for treating adverse reactions of digestive tracts in radiotherapy and chemotherapy of tumors and preparation method thereof |
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Application publication date: 20130731 |