CN104352486B - 5 hydroxymethyl furfural purposes in preparing stomach motility enhancing medicine - Google Patents
5 hydroxymethyl furfural purposes in preparing stomach motility enhancing medicine Download PDFInfo
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- CN104352486B CN104352486B CN201410450601.2A CN201410450601A CN104352486B CN 104352486 B CN104352486 B CN 104352486B CN 201410450601 A CN201410450601 A CN 201410450601A CN 104352486 B CN104352486 B CN 104352486B
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
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Abstract
The invention discloses a kind of 5 Hydroxymethylfurfural purposes in preparing stomach motility enhancing medicine, belong to pharmaceutical technology field, selecting Mouse Stomach emptying experiment is pharmacological basis, emptying test method: utilize endoscope clinically or observe the situation that certain material disappears at gastric, and judging the air emptying function of stomach;Experimentation then according to injection and the retention amount of gastric content, is directly measured;By pharmacological evaluation, this research, with methyl orange as index, proves that 5 Hydroxymethylfurfural have the effect of rush gastric emptying.
Description
Technical field
The invention belongs to pharmaceutical technology field, relate in particular to a kind of 5 hydroxymethyl furfural and preparing stomach motility enhancing medicine
In application.
Background technology
5 hydroxymethyl furfural is the aldehydes that the monosaccharide compounds such as glucose produce in the dehydration of the condition such as high temperature or weak acid
Compound, typically after concocting or heating, content can raise, and this compound all contains time composition in most Chinese medicines.In the past to 5-
The research of Hydroxymethylfurfural thinks there is the control of content in medicine and food, but nearest research finds that it has the newest medicine
Reason effect (Fu Ziqin, Wang Mingyan, Cai precious prosperous .5-Hydroxymethylfurfural 5-HMF the Research Status [J] China in Chinese medicine
Chinese medicine academic periodical, 2008,26(3) 508-510).:
(1) resist myocardial ischemia
In recent years, finding in the studying of compound prescription of Chinese herbs, 5 hydroxymethyl furfural has certain function of resisting myocardial ischemia.To raw arteries and veins
The chemical composition dissipated is studied, and from its dividual decoction, one new component of isolated, is accredited as through UV, IR, MS and H NMR spectroscopy
5-HMF .Meanwhile, research finds, single medicinal material without 5-HMF, can produce a small amount of 5-before decoction after single Fructus Schisandrae Chinensis decocting
HMF, does not finds Radix Ginseng, Radix Ophiopogonis 5-HMF in decocting liquid, and SHENGMAI SAN side entirely and Radix Ophiopogonis and 5-HM in the decocting liquid of Fructus Schisandrae Chinensis compatibility
The content of F significantly increases, thus it is speculated that 5-HMF generates may be relevant with Fructus Schisandrae Chinensis acidity, and its content is mainly affected by Radix Ophiopogonis.Enter
One step carries out finding after pharmacodynamic study, full side close the drug effect decocted be substantially better than the party single decoct combination of two compatibility or tripartite single
The drug effect of mixing after Jianing, thus it is speculated that this result may be relevant with 5-HMF contained therein and content thereof.Separating obtained 5-HMF are entered
Row Pharmacodynamic is tested, and research shows, 5-HMF can reduce LDA content in myocardial ischemia mice serum, reduces myocardial ischemia little
MDA content in Mus cardiac muscular tissue, after pointing out SHENGMAI SAN the most just to decoct, the change of chemical composition is conducive to its function of resisting myocardial ischemia,
Its generation is favourable to compound recipe entirety curative effect, is one of material base of resisting myocardial ischemia of SHENGMAI SAN.
(2) antioxidation
The 5-HMF that former three medical materials of isolation identification do not have from SHENGMAI SAN decoct in recent years, it was demonstrated that 5-HMF is except having the anti-heart
Outside myocardial ischemia effect, also there is good antioxidation.Meanwhile, it has been reported that containing 5-HMF in Maotai, have stronger resisting
Oxidisability, is of value to oral health, and has function of resisting myocardial ischemia equally.
(3) Ca2+Antagonistic activity
Research finds, can generate 5-HMF, have Ca after the processed process of preparing Chinese medicine of sucrose contained in prunus mume (sieb.) sieb.et zucc. fruit (such as Fructus Mume)2+Short of money
Resistant activity, the activity that the guinea pig colonic belt having stronger antagonism to be caused by potassium ion shrinks.Meanwhile, Fructus Mume has antiallergic work
With, its antiallergic mechanism is probably the result of the anaphylactogen in the free antibodies that nonspecific stimulation produces and in intrusive body, has
People thinks that this mechanism of action may be relevant with 5-HMF contained therein.
(4) hemorheology is improved
Research finds, Radix Rehmanniae generates 5 HMF during steaming, and extends with steaming time, 5-HMF content in Radix Rehmanniae Preparata
Increasing, after concocting ripe Radix Rehmanniae, its content increases about 20 times.And pharmacodynamic experiment finds that Radix Rehmanniae Preparata can be red carefully by improvement
The erythrocyte such as born of the same parents' deformability, RCA body formation are dynamic, and improve hemorheology by making fibrinolytic system function strengthen
Learn, thus present blood promote effect, compared with Radix Rehmanniae Preparata, health product acts on more weak in this respect, this may with both contained by 5-
The difference of HMF content is relevant.It addition, from the yellow Fructus Pruni originating in Japan isolated 5-HMF, confirm 5-equally by experiment
HMF has certain effect in terms of improving hemorheology.
(5) glycyrrhizic acid metabolism is affected
It has been reported that, containing the composition such as glucose, sucrose, 5-HMF in Mel, these 3 kinds of composition rabbit respectively are administered orally to
After medicine, observe it to glycyrrhizic acid in rabbit body and the impact of enoxolone metabolic condition.Result shows, 5-HMF can suppress Radix Glycyrrhizae
Subacid is oxidized to 3-dehydrogenation enoxolone, increases enoxolone absorption in vivo, thus promotes glycyrrhizic acid and enoxolone
Suppression tumor, antiinflammatory, the effect of reduction blood cholesterol.
(6) other
In recent years, people is had within 30 days, to cause rat with the perfusion of mitochondrial respiratory chain complex IV inhibitor sodium azide Micropump constant speed
Neuronal energy dysbolismus and ability of learning and memory lower, thus study kidney-nourishing tcm drug Fructus Corni monomer component 5-HMF effect,
Result shows, 5-HMF can cause neurocyte mitochondrial transmembrane potentials and decline by antagonism sodium azide, and can raise and turn AD patient's line
The mitochondrial membrane potential of mitochondrial DNA fused cell.
Summary of the invention
A kind of 5 hydroxymethyl furfural that it is an object of the invention to provide purposes in preparing stomach motility enhancing medicine.
The present invention be select Mouse Stomach emptying experiment for pharmacological basis (emptying test method: utilize clinically endoscope or
Observe the situation that certain material disappears at gastric, and judge the air emptying function of stomach;Experimentation is then according to the injection of gastric content
And retention amount, directly measure (Xu Shuyun etc., 2006);This research is (king is supporting just etc., 2008) with methyl orange as index.Pass through
Pharmacological evaluation proves that 5 hydroxymethyl furfural has the effect promoting gastric emptying
Detailed description of the invention
The present invention is with mice as laboratory animal, observes 5 hydroxymethyl furfural and the stomach motility enhancing effect of preparation thereof, specifically
Test as follows:
1. instrument and material
1.1 instrument
AL-204 type electronic balance (Shanghai prunus mume (sieb.) sieb.et zucc. Teller-Tuo Li Instrument Ltd.)
TU-1810 ultraviolet-uisible spectrophotometer (Beijing Pu Xi all purpose instrument Co., Ltd)
SK250LH-ultrasonic cleaner (Shanghai Ke Dao Instrument Ltd.)
0412-1 table-type low-speed centrifuge (Shanghai Medical apparatus company limited operating theater instruments factory)
Material
Positive control drug motilium (Xian-Janssen Pharmaceutical Ltd., lot number 110316588)
5 hydroxymethyl furfural (Industrial Co., Ltd. of upper ingression section, lot number Q-00469)
5 hydroxymethyl furfural tablet, capsule, granule are to make by oneself by following example, and remaining is domestic reagent.
1.3. laboratory animal
Kunming kind SPF mice, is provided by Guiyang Medical College animal center, the laboratory animal quality certification number: SCSK(Guizhou Province) lot number:
2004-0001。
2. method and result
2.1 prepare for reagent: take 5 hydroxymethyl furfural 2g(200mg Han 5 hydroxymethyl furfural respectively), use distilled water 20mL
Diluted for use;Separately take 5 hydroxymethyl furfural tablet 6g(200mg Han 5 hydroxymethyl furfural), 5 hydroxymethyl furfural capsule 6g(contains
5 hydroxymethyl furfural 200mg), it is suspended in 20mL distilled water standby;Take 5 hydroxymethyl furfural granule 100g(methylol bran Han 5-
Aldehyde 200mg), it is suspended in 75mL distilled water standby with distilled water;
Prepared by 2.2 positive drug motilium water: take motilium tablet 2g(200mg Han motilium), add distilled water 20ml, fully
After stirring and dissolving standby.
Test sample content of dispersion:
5 hydroxymethyl furfural: 0.01g/ml
Motilium: 0.01 g/ml
5 hydroxymethyl furfural tablet: 0.01g/ml
5 hydroxymethyl furfural capsule: 0.01g/ml
5 hydroxymethyl furfural granule: 2.7mg/ml
The impact of 2.3 Mouse Stomach emptyings
Take mice 40, male and female half and half, body weight 18~22g, be randomly divided into 5-HFM tablet group, 5-HFM capsule group, 5-
HFM group, positive motilium group, blank group.Blank group gavage gives normal saline, and other group gavages give corresponding medicine
Thing solution, every mice is administered 0.1ml/10g, continuous gavage 4 days;Separately take every mice of 5-HFM granule group to be administered
0.325ml/10g, continuous gavage 4 days;After last is administered 1 hour, gavage 0.5% methyl orange solution 0.2ml/ every respectively, 30
After clock, mice cervical dislocation is put to death, and takes out complete stomach, rubs, drip appropriate 5% in the test tube equipped with 10ml normal saline
NaHCO3 solution, adjusting solution ph is about 7, centrifugal 15 minutes, takes the supernatant, with ultraviolet-uisible spectrophotometer in wavelength
Absorbance A value is surveyed at 463nm.Result see table 1-1,
The impact that Mouse Stomach is emptied by table 1-1 reactive compound
Sequence number | Number of animals (only) | Dosage (g/kg/d) | Methyl orange absorbance A | P value |
5-HM | 10 | 0.1 | 0.925** | 0.00356** |
Embodiment 1 | 10 | 0.1 | 0.924** | 0.00539** |
Embodiment 2 | 10 | 0.1 | 0.919** | 0.00673** |
Embodiment 3 | 10 | 0.1 | 0.927** | 0.00481** |
Motilium | 10 | 0.1 | 0.936** | 0.00334** |
Blank | 10 | – | 0.830 | 0 |
* P < 0.05, * * P < 0.01 is compared respectively with blank group
Proved by pharmacological evaluation, 5 hydroxymethyl furfural, 5 hydroxymethyl furfural tablet, 5 hydroxymethyl furfural capsule, 5-
Hydroxymethylfurfural granule, motilium P value are respectively less than 0.01, illustrate that it has pole significant difference compared with blank group.
Effect to be reached, treatment time and administering mode are depended in metering;With the metering of motilium as reference, these
Metering is usually adult's tablet oral every day, capsule 300-900mg, granule 5-15g, and unit dosage is 5 hydroxymethyl furfural
10-30mg。
Embodiment 1: there is the following composition tablet containing 5 hydroxymethyl furfural 10mg according to routine techniques preparation
5 hydroxymethyl furfural 10mg
Starch 36mg
Dextrin 30mg
Carboxymethylstach sodium 8mg
Magnesium stearate 53mg
Sodium carboxymethyl cellulose 53mg
Starch slurry 18% 110mg
Embodiment 2: there is the following composition capsule containing 5 hydroxymethyl furfural 10mg according to routine techniques preparation
5 hydroxymethyl furfural 10mg
Starch 135mg
Pulvis Talci 65mg
Carboxymethylstach sodium 45mg
Dibastic sodium phosphate 35mg
Magnesium stearate 10mg
Embodiment 3: there is the following composition granule containing 5 hydroxymethyl furfural 10mg according to routine techniques preparation
5 hydroxymethyl furfural 10mg
Dextrin 450m g
Sucrose 4540mg
The above, be only presently preferred embodiments of the present invention, and the present invention not makees any pro forma restriction,
Any without departing from technical solution of the present invention content, any simply repaiied according to what above example made by the technical spirit of the present invention
Change, equivalent variations and modification, all still fall within the range of technical solution of the present invention.
Claims (1)
1. a 5 hydroxymethyl furfural is as sole active composition purposes in preparing stomach motility enhancing medicine.
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Address after: 551400 High-tech Industrial Planning Zone, Qingzhen City, Guiyang City, Guizhou Province (No. 109, Lishan Road) Patentee after: Guizhou Biotechnology Research and Development Base Co.,Ltd. Address before: No. 17, Nanchong Lane, Jiefang West Road, Guiyang City, Guizhou Province, 550004 Patentee before: GUIZHOU BIOTECHNOLOGY RESEARCH AND DEVELOPMENT BASE |