CN1506046A - Active compound of Baojiwan pill for resisting diarrhea and reducing gastrointestinal illness - Google Patents
Active compound of Baojiwan pill for resisting diarrhea and reducing gastrointestinal illness Download PDFInfo
- Publication number
- CN1506046A CN1506046A CNA031238475A CN03123847A CN1506046A CN 1506046 A CN1506046 A CN 1506046A CN A031238475 A CNA031238475 A CN A031238475A CN 03123847 A CN03123847 A CN 03123847A CN 1506046 A CN1506046 A CN 1506046A
- Authority
- CN
- China
- Prior art keywords
- compositions
- magnolol
- chloride ion
- isoimperatorin
- isoarborinol
- 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
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention provides treating method of medical symptoms caused by abnormal chlorine ion flow, and the method is to use medicinal composition containing active components from Chinese medicine Baojiwan pill. The medicinal composition contains one or several of the following compounds: magnolol, cylindrin and isoenbolaterine, as well as physiologically acceptable carrier. In the optimal scheme, the present invention is used in treating gastrointestinal diseases, such as diarrhoea and constipation.
Description
The cross reference of related application
The application require the calendar year 2001 USSN 60/339,752 that proposes of December 17 days as priority, enroll the application in full as a reference.
Invention field
The present invention relates to adopt the medicine composite for curing that contains Chinese medicine Health pill (BJW) active component to have the method for unusual chloride ion flow symptom.Especially, the present invention is directed to gastrointestinal symptoms as diarrhoea and constipation.
Background of invention
Regulate chloride ion and cross over the key that the epithelial cell flow is interior electrolyte of maintenance body and liquid dynamic equilibrium.Unusual chlorine (Cl
-) ion-flow rate causes some different pathophysiology symptoms, comprises Cystic fibrosis, polycystic kidney disease etc.One of the most general disease is a diarrhoea, particularly communicable secretion diarrhoea, and wherein, the over-drastic prostaglandin secretion that choiera toxin or inflammation cause makes chloride and moisture secrete rise.In the middle of all made human generation diarrheal enteropathogen, cholera toxin stimulated chloride ion and liquid secretion by for good and all activating adenyl cyclase and cAMP, causes the most fatal symptom.
According to the report of The World Health Organization (WHO), diarrhoea is to cause one of main causes of death in the world, particularly generally is subjected to the developing country of germ contamination at food and water.This problem is especially serious in child and infant, has every year 5 years old the child of 5,000,000 age less thaies of surpassing to die from malnutrition, diarrhoea and dehydration.Most of used diarrhea is as the motion and the wriggling of retrostalsis medicine inhibition stomach, and some then is adsorbent and antibacterial.Wherein do not have a kind of medicine can suppress electrolyte and liquid secretion, this is to cause the diarrheal reason in many serious situations.The retrostalsis medicine may cause central nervous system's side effect, and unwanted gastrointestinal effects, comprise nauseating, the vomiting and abdominal discomfort.In addition, although considerable Chinese medicine provides the treatment diarrheal to select, their active component is uncertain usually and their mechanism of action is unclear.Therefore, but be necessary to seek the excretory medicine of a kind of specific regulating chloride and water with known activity composition in this area.The present invention has filled up this blank and has satisfied other needs.
Brief summary of the invention
One aspect of the present invention provides the method for treatment by the caused medical symptom of unusual chloride ion flow, and this method comprises pharmaceutical composition and the physiology's acceptable carrier that the patient is used the treatment effective dose.Described pharmaceutical composition comprises and is selected from magnolol (claiming magnolol again), honokiol, and any or two or more the combination arbitrarily in Isoarborinol methyl ether. and the isoimperatorin, and the physiology goes up acceptable carrier.In certain embodiments, described patient is human.
In one embodiment, medical symptom is secreted increase institute by chloride ion and moisture and is caused, as some gastroenteropathy.These diseases can be by virus, antibacterial (for example, cholera toxin), neuroendocrine tumor, parasite, or the caused diarrhoea of HIV.This method can also be used to treatment and secretes caused other symptom of increase by chloride ion and moisture, includes but not limited to polycystic kidney disease and inflammatory bowel.
In another embodiment, disease is secreted reduction institute by chloride ion and moisture and is caused, as some gastroenteropathy (for example, constipation) and Cystic fibrosis.
On the other hand, the invention provides the method for treatment by the unusual caused medical symptom of chloride ion flow, this method comprise to the patient use the treatment effective dose by magnolol, honokiol, pharmaceutical composition that Isoarborinol methyl ether. and isoimperatorin are formed and physiology go up acceptable carrier.
Again on the one hand, the invention provides treatment diarrheal method, this method comprises and mainly comprises pharmaceutical composition any or two or more combination arbitrarily and the physiology's acceptable carrier that is selected from magnolol, honokiol, Isoarborinol methyl ether. and the isoimperatorin to what the patient used the treatment effective dose.
Again on the one hand, the invention provides treatment diarrheal method, this method comprises and only comprises magnolol, honokiol, the pharmaceutical composition of Isoarborinol methyl ether. and isoimperatorin, and physiology's acceptable carrier to what the patient used the treatment effective dose.
Again on the one hand, the present invention also provides the method for regulating the chloride ion flow, and this method comprises uses treatment to be selected from magnolol, honokiol mainly comprising of effective dose to the patient, any in Isoarborinol methyl ether. and the isoimperatorin or the pharmaceutical composition of two or more combination arbitrarily; And physiology's acceptable carrier.
In the one side, the invention provides the method for treatment constipation again.This method comprises uses mainly comprising or comprise and being selected from magnolol of treatment effective dose to the patient, honokiol, pharmaceutical composition and physiology's acceptable carrier any or two or more combination composition arbitrarily in Isoarborinol methyl ether. and the isoimperatorin.But constipation may be due to and is not limited to following symptom, human primary gastrointestinal cancers, the BehectShi disease, the neuropathy of elementary or secondary intestinal, the gastrointestinal dysfunction in the parkinson, irritable bowel syndrome, chronic constipation, the bowel dysfunction in the Hirschsprung transports constipation slowly, gastrointestinal dysfunction in the Alzheimer, or the treatment of chronic opioid.
Brief description of the drawings
The chloride ion secretion that Fig. 1 causes by honokiol inhibition cholera and forskolin.
The chloride ion secretion that Fig. 2 causes by Isoarborinol methyl ether. inhibition cholera and forskolin.
The chloride ion secretion that Fig. 3 causes by isoimperatorin inhibition cholera and forskolin.
Fig. 4 suppresses the diarrhoea that magnesium sulfate causes by BJW.
Fig. 5 stimulates the secretion of chloride ion by BJW and Cortex Magnoliae Officinalis Chinese medicine composition.
The present invention describes in detail
Summary
The invention provides Chinese medicine Health pill (BJW), also claim Po Chai Pill and Bao Ji Pill The using method of reactive compound, this Chinese medicine is made up of kind of medicinal herbs surplus ten, at present as wide spectrum antidiarrheal Medicine and caccagogue.
Now from Health pill, isolated four kinds of reactive compounds, magnolol, honokiol, imperatorin, And isoimperatorin, the chloride ion secretion that they can suppress separately excessive cAMP mediation is also And when no hypersecretion, stimulate secretion. The separation of these compounds and the merit of separated compound The effect card takes into account the prescription of the pharmacy composition with the above-mentioned active component of various combination, and what be fit to is every Individual component makes the desired effects optimization, and reduced side effects is to minimizing. In preferred embodiments, The present invention comprises magnolol, honokiol, imperatorin, or in the isoimperatorin any, Or arbitrarily two or more combination. In optional embodiment, the present invention only comprises magnolol, Honokiol, imperatorin, isoimperatorin, and effective carrier on a kind of physiology.
As effective conditioning agent of chlorion flow, these compounds are especially unusual for resulting from The chlorion flow comprises that secreting increase and chlorion and moisture by chlorion and moisture secretes and reduce institute and cause The treatment of pathology symptom. In certain embodiments, the method is for polycystic kidney disease, inflammation Property intestinal disease, cholera and tumour fibre modification etc. Most preferably, the method is for enterogastric diseases, Comprise diarrhoea and constipation. Diarrhoea can by virus, bacterium, neuroendocrine tumor, parasite or HIV causes. The useful effect that these compounds are secreted chloride and moisture causes various factors The GI disease provides treatment, is the god that the antidiarrheal agent of inhibition wriggling is followed and there is not its Main Function mode Through system's side effect.
In other embodiments, these compounds are for other enterogastric diseases or have the stomach of impact The treatment of the disease of the symptom of intestines system. In some example, these disease/symptoms result from chlorination Logistics capacity unusual, but they result from other factors in other example. For example, chemical combination of the present invention The performance that thing suppresses water and chlorion flow can be used for treatment diarrhoea, no matter and its cause how. Protect It is right that Ji ball and the plant extracts that contains compound subset of the present invention (subunit) all are shown The inhibition of noninfectious diarrhea. In addition, the performance of The compounds of this invention stimulation water and chlorion flow can The symptom that is used for the treatment of a lot of diseases relevant with constipation, such as human primary gastrointestinal cancers, Behect ' s disease, elementary or Secondary enteron aisle neuropathy, the gastrointestinal dysfunction in the Parkinson's disease, irritable bowel syndrome, chronic Constipation, the bowel dysfunction in the Hirschsprungs disease transports constipation, in the Alzheimer's slowly Gastrointestinal dysfunction and the side effect of chronic opioid treatment.
In other side, the present invention includes the combination of this active component and other treatment effective agent. Group Closing the idea for the treatment of is utilized in current medical practice widely. Adopt two or more Medicine for same illness or biochemical path carries out the pathology treatment, and is corresponding with respect to independent use Single medicine of planting of dosage, its result for the treatment of is better and can reduce side effect sometimes. Preferably, this activity Composition is combined administration with other medicament of regulating chloride ion secretion or the disorder for the treatment of stomach and intestine.
Definition
Unless specify in addition, following term used in this application has the following implication that is attributed to them.
The administration of the present composition " treatment effectively " amount is defined as the effective dose of realizing the result that needs in the dosage of needs and time.The treatment effective dose of the present composition can be according to the morbid state such as individuality, age, sex, and factors vary such as body weight.Dosage regimen can be adjusted so that best therapeutic effect to be provided.For example, can administration every day several times divided dose or be administered once in one day or many days.
" pharmaceutically acceptable salt " for being suitable for the patient, for example, and the organic or inorganic salt of mammal or human administration.
" physiology's acceptable carrier or diluent " is for being suitable for the vehicle to mammal such as human administration.Suitable diluent or carrier comprise sterile solution such as saline, aqueous buffer solution, glycerol ex hoc genus anne thing.
Term " separation ", " purification " or " biology is pure " relate to fully or are substantially free of usually the material of the component of finding in its native state of following with it.Purity and homogeneity be operational analysis chemical technology such as polyacrylamide acrylamide gel electrophoresis or high effective liquid chromatography for measuring typically.The chemical compound that accounts for main component in preparation is by abundant purification, and especially, this chemical compound preferably has 85% purity at least, more preferably has 95% purity at least, and the purity that most preferably has 99% at least.
" unusual chloride ion flow " refers to deviate from some sense the motion that NHS's chloride ion is crossed over cell membrane.The chloride flow can be measured according to method well known to those skilled in the art.For example, the flux measurement of short circuit current technology and use isotope or fluorescence.
The method of " treatment " patient medical symptom refers to reduce or suppress symptom, perhaps promotes or provide the method for treatment.By using the application's disclosed method or using standard method well known by persons skilled in the art, the medical conditions symptom that alleviates can be measured by big metering method.In order to check the degree of sx, compare with potential modulators for treatment experimenter (for example, rat) and with the control sample of no regulator.
The method of separation or synthetic compound
The chemical formula of The compounds of this invention and structure are disclosed in JP4368324 (magnolol and honokiol), JP5025008 (Isoarborinol methyl ether. and isoimperatorin), and JP9157166 (Isoarborinol methyl ether. and isoimperatorin).
By magnolol, honokiol, Isoarborinol methyl ether., the compositions of forming with isoimperatorin of the present invention can be a plant extract, from the chemical compound of plant extract purification or the mixture of chemical compound, perhaps with plant extract in the chemical compound found synthetic again chemical compound with same or similar chemical constitution.The method for preparing extract all has description in the application and this area, for example: JP 426403 (" from contain the magnolol plant, extracting magnolol "), be extracted in Garcia-Argaez etc. for Isoarborinol methyl ether., Planta Med 66 (3): 279-81 has description in (2000), extraction for isoimperatorin, at Yang etc., J Chromatogr 883 (12): 67-73 has description in (2000).Said extracted thing and chemical compound also can obtain from the market.
Test compound changes the mensuration of the ability of chloride ion and water flux density
The activity of above-claimed cpd can be according to the described assay method test of the application.Chemical compound is regulated the excretory ability of liquid and can be measured by algoscopy in the various external and bodies well known by persons skilled in the art.Preferably, before or after the The compounds of this invention administration, induce fluid accumulation by inflammatory stimulus (for example, using prostaglandin).Fluid accumulation can (for example: gram liquid/gram intestinal) measure to determine the inhibition degree under the situation about existing be with or without chemical compound.For being described in more detail of method, referring to Robert etc., Prostaglandins 11 (5): 809-28 (1976); Rani etc., JEthnopharmacology 68 (1-3): 315-9 (1999); Kislofier etc., Gastroenterology72 (3): 462-8 (1977); Cunha Ferreira etc., Acta Paediatr 81 (1): 46-50 (1992).
The ability of chemical compound adjusting chloride ion secretion can be by the various external and interior algoscopy mensuration of body well known by persons skilled in the art.Preferably, be with or without test compound in the presence of, the mammal cell line that any medicament (for example, forskolin or cholera toxin) that employing can increase the cAMP level stimulates the secretion chloride ion is (for example, T84, human colon's cell line) induce chloride ion secretion.The chloride secretion level can be measured by any method known to those skilled in the art, but flux measurement (Donowitz M etc., the Annu.Rev.Physiol 48:135-150 (1986) of preferred short circuit current technology or use isotope or fluorescence; McCabe RD etc., Am J Physiol 247 (4 Pt1): G411-8 (1984); Foster ES etc., J.Clin Invest 77:228-235 (1986); Chao etc., J Membr Biol 113 (3): 193-202 (1990); Fondacaro etc., J Pharmacol ExpTher 247 (2): 481-6 (1988)).
Effect can use diarrhoea well known by persons skilled in the art or animal models of constipation to measure in the body of these chemical compounds.Preferably, mammal (for example, rat) diarrhoea causes by magnesium sulfate or Radix Et Rhizoma Rhei, uses this chemical compound that it is treated, and its effect is determined by comparing intestinal transportation and diarrhoea, and the employing method known to those skilled in the art is measured.For example, Fiocchi etc., Life Sci31:2221-3 (1982); Ozaki etc., Jpn J Pharmacol 80:93-96 (1999).Mammiferous constipation can be passed through morphine, verapamil, and atropine, or amitriptyline causes (Tsusumi etc., Biol Pharm Bul123 (5): 65 7-9 (2000); Bianchi etc., Gastroenterology 85 (4): 852-8 (1983); Calignano etc., Gen Pharmacol 23 (4): 753-6 (1992)).Pharmaceutical composition and administration
In certain embodiments, pharmaceutical composition of the present invention comprises following compounds: magnolol, honokiol, Isoarborinol methyl ether., and any in the isoimperatorin, two kinds, three kinds or four kinds.In particularly preferred scheme, pharmaceutical composition of the present invention comprises independent magnolol, or magnolol and other chemical compound (honokiol, Isoarborinol methyl ether., and isoimperatorin) any combination in, or all four kinds of chemical compounds (magnolol, honokiols, Isoarborinol methyl ether., and isoimperatorin) together.
The last acceptable carrier of physiology also depends on the mode of pharmaceutical preparation on the other hand on the one hand by the component decision (for example, the Health pill composition of active components) of giving medicine.Therefore, pharmaceutical composition of the present invention have appropriate formulation miscellaneous (referring to, Remington ' sPharmaceutical Sciences for example, 17
ThEd., 1989).Administration can adopt any mode easily to carry out, and is for example oral by injection, sucks transdermal effect, or rectally.Determine with external model in the body that dosage and administration can use the application to provide.
Be suitable for oral preparation and can comprise (a) liquid solution, be suspended in the diluent, this diluent such as water, saline or PEG 400 as effective dose Health pill active component; (b) capsule, sachet or tablet respectively contain as liquid, solid, the scheduled volume of the active component of granule or gel; (c) suspension in suitable liquid; And (d) suitable Emulsion.Tablet form can comprise one or more lactose, sucrose, mannitol, Sorbitol, calcium phosphate, corn starch, potato starch, microcrystalline Cellulose, gel, silica sol, Talcum, magnesium stearate, stearic acid, and other excipient, coloring agent, filler, binding agent, diluent, buffer agent, wetting agent, antiseptic, fumet, dyestuff, disintegrating agent, and pharmaceutically compatible carrier.The dragee form can contain active component in flavoring agent, for example, sucrose also can be the pastille that comprises active component in inert base, as gel and glycerol or sucrose and arabic gum Emulsion and gel and the analog that contains carrier known in the art except that active component.
That select, independent or with the bonded chemical compound of other suitable component can be manufactured into into aerosol (that is, they can by " spraying ") through inhalation.Aerosol can be placed in the acceptable Compressed Gas, as dichlorodifluoromethane, and propane, nitrogen and analog thereof.
Be suitable for parenteral, as passing through vein, muscle, Intradermal, endoperitoneal and preparation subcutaneous administration comprises wherein can comprise moisture and anhydrous isotonic sterile injection solution, and this solution can comprise antioxidant, buffer agent, antibacterial, the solute of preparation and the isoosmotic preparation of intended recipient's blood, and can comprise suspending agent, solubilizing agent, thickening agent, the moisture and anhydrous sterile suspensions of stabilizing agent and antiseptic.
This preparation can provide with single dose or multiple dose encapsulation, as ampoule and phial.According to the present invention, the effect that should in patient's body, be enough to produce useful therapeutic response along with the past of time to patient's dosage.This dosage by the effect of used special composition, need patient's the situation of treatment and patient's body weight or surface area to determine.The existence of any adverse side effect that the size of dosage also produces in special patient's body according to the administration of following particular components, nature and extent is determined.
When needing the effective dose of component of administration when determining treatment or prevention symptom, the doctor estimates the circulating plasma level of this component, component toxicity, the progress of disease and anti-component production of antibodies.In general, the about 1 mg/kg body weight of dose equivalent, wherein the mixture of chemical compound can be any ratio.
For administration, compositions of the present invention can be determined according to the side effect of component and medication patient's body weight and total health status under the LD 50 of component and the various concentration.Administration can be undertaken by single dose or divided dose.
Be used as with reference to enrolling the application as each specific publication of quoting or patent application, the application is all enrolled in all publications quoted in this description and patent application as a reference.
Although foregoing invention is understood by explanation and has been carried out comparatively detailed description for example for the ease of clear, but, according to explanation of the present invention, obviously be readily understood that for those of ordinary skills certain changes and modifications can be carried out under the prerequisite of design road that does not break away from appended claim or scope.
Embodiment
The following example furnishes an explanation, but does not limit invention required for protection.
Present embodiment explanation Health pill and active component thereof, magnolol, honokiol and Isoarborinol methyl ether. suppress the ability of the inductive fluid accumulation of PGE2 in rat.Use the Sprague-Dawley rat of any sex of body weight between 220 and 250 grams, 8 one group.Use the PGE that revised
2Inductive intestinal smoulders enteropooling) (Robert etc., Prostaglandins 11 (5): 809-28 (1976)) for mensuration.At PGE
2Administration (100 μ g/ kilograms, i.g.) 60 minutes before, with trial drug or vehicle to the rat gastrointestinal tract administration.Use PGE
2Before the treatment, with Health pill administration (i.g.1.6 gram/kilogram, the human dosage that 2x recommends) once a day, totally two days.Recording the intestinal juice volume gathers/and restrain body weight and calculate the % suppression ratio, as shown in table 1.This test shows that Health pill and active component thereof are to PGE
2Inductive fluid accumulation is inhibited.Under the dosage of the human dosage that 2x recommends, the effect of Health pill and magnolol is obviously more effective than the common diarrhea loperamide that obtains on the market.
Table 1. Health pill and described component are to PGE
2The effect of inductive fluid accumulation
The type dose fluid gathers rate (FA) secretion and suppresses
(fluid g/g intestinal) (%)
Conventional carrier 2.47 ± 0.13
PGE2 model 100 μ g/kg 12.87 ± 2.03
###
BJW 1.6g/kg 3.10±0.35
*** 94
Magnolol 2mg/kg 7.06 ± 1.18
*56
Isoarborinol methyl ether. 2mg/kg 8.87 ± 1.93 39
Loperamide 2mg/kg 5.09±1.40
* 75
###P＜0.01 is compared with normal group
P＜0.05,
* *P＜0.01 is compared with model group
Secretion % suppression ratio=(FA
Model-FA
Test)/(FA
Model-FA
Normal) * 100%
Present embodiment explanation Health pill active component is at secretion Cl
-Human colon's cell line T84 in to the activatory Cl of cAMP
-Excretory inhibitory action.Because causing the activation of the adenyl cyclase of cAMP rising is to comprise PGE
2Inductive recessive machine-processed at interior many secretory diarrheal with the inductive diarrhoea of cholera toxin, so the adenylate cyclase enzyme activator, forskolin (10 μ M), and the Cl of the inductive leap of cholera toxin T84 cell monolayer
-Secretion all is examined.Honokiol, Isoarborinol methyl ether. and isoimperatorin are induced and the inductive excretory inhibiting concentration-response curve of cholera toxin such as Fig. 1 forskolin, shown in 2 and 3, have close IC
50S (4-7 μ g/ milliliter).These results prove that the activatory Cl-secretion of described reactive compound and inhibition cAMP has similar effect.
The following example explanation Health pill is to other effect with the inductive diarrhoea model of experimental technique.
Present embodiment explanation Health pill is to magnesium sulfate-inductive rat diarrheal effect.The Health pill of test various dose, the result as shown in Figure 4.When dosage is 1.6 gram/kilograms (the human dosage that 2x recommends) the inductive diarrhoea of magnesium sulfate is obtained effectively to suppress effect.This diarrhea Herba Andrographis than another kind of Chinese medicine base is more effective, and dosage is 0.25 gram/kilogram (the human dosage that 10x recommends).Because the recessive mechanism of the inductive diarrheal of magnesium sulfate has multiple, comprise owing to increase osmotic pressure and cause the increase fluid volume, the mobility stimulates and secretion, by Health pill to this diarrhoea model suppress fully show that Health pill and component thereof can also act on the mechanism except that secreting.
Present embodiment explanation Health pill is to the effect of the inductive rat diarrheal of Radix Et Rhizoma Rhei.Radix Et Rhizoma Rhei is well-known by stimulating bowel movement and suppressing Na+ and the chronic diarrheal Chinese medicine of inducing of Liquid Absorption.Along with the weight of animals alleviates and the body temperature reduction, this model appears to the imitation chronic diarrhea.Radix Et Rhizoma Rhei solution (8 ml/kg) is given 10 days once a day to 10 one group rat administration.(6 ml/kg i.g.) detect administration in the 8th day and at the 11st day for trial drug or vehicle.The result is as shown in table 2.Health pill produces inhibitory action in dose-dependent mode.Although it is lower that Health pill is compared other diarrhoea model to the effect of this diarrhoea model, more effective than another kind of Chinese medicine base diarrhea Herba Andrographis.
The diarrheal effect that table 2 Health pill brings out Radix Et Rhizoma Rhei
Type dosage intestinal diarrhoea suppresses
(g/kg) (g) (％)
Conventional carrier 9.1 ± 1.0
Model vehicle 17.7 ± 1.9
###
BJW 0.4 14.5±1.3 37
BJW 0.8 12.1±1.3
* 58
BJW 1.6 11.7±1.3
* 70
CXLP 0.25 15.2+1.5 29
###P＜0.01 is compared with normal group
*＜0.05, compare with model group
Diarrhoea % suppression ratio=(ID
Model-ID
Test)/(ID
Model-ID
Conventional) * 100%
Present embodiment explanation Health pill and active component thereof are to the Cl in human colon's cell
-Stimulation with liquid secretion.When not having other stimulation, Health pill and Cortex Magnoliae Officinalis stimulate Cl
-Secretion (Fig. 5), magnolol and honokiol are derived from Cortex Magnoliae Officinalis and are obtained, and therefore, illustrate that Health pill and active component thereof have the lateral reactivity as aperient.
Disclosed embodiment of the application and embodiment just in order to be used for explanation, can propose various modifications or variation to those skilled in the art thus, and these include in the scope of the application's design and scope and appended claim.List of references is all enrolled in all publications, patent and patent application that the application quoted.
Claims (21)
1. the medical symptom that caused by unusual chloride ion flow of a treatment is or/and regulate the pharmaceutical composition of chloride ion flow and fluid secretion, the magnolol that is selected from that comprises the treatment effective dose, honokiol, Isoarborinol methyl ether., with any in the isoimperatorin or multiple combination arbitrarily, and the physiology goes up acceptable carrier.
2. the compositions of claim 1, wherein said compositions comprises magnolol.
3. claim 1 compositions, wherein said compositions comprises honokiol.
4. the compositions of claim 1, wherein said compositions comprises Isoarborinol methyl ether..
5. the compositions of claim 1, wherein said compositions comprises isoimperatorin.
6. the compositions of claim 1, wherein said compositions comprises magnolol and honokiol.
7. the compositions of claim 1, wherein said compositions comprises magnolol and Isoarborinol methyl ether..
8. the compositions of claim 1, wherein said compositions comprises magnolol and isoimperatorin.
9. the compositions of claim 1, wherein said compositions comprises magnolol, honokiol, Isoarborinol methyl ether., and isoimperatorin.
10. according to the compositions of claim 1, wherein said medical symptom results from chloride ion and the excretory increase of water.
11. according to the compositions of claim 10, wherein said medical symptom is a gastroenteropathy.
12. according to the compositions of claim 11, wherein said disease is diarrhoea.
13. according to the compositions of claim 12, wherein said diarrhoea results from virus, antibacterial, neuroendocrine tumor, parasite, or HIV.
14. according to the compositions of claim 13, wherein said diarrhoea results from cholera toxin.
15. according to the compositions of claim 10, wherein said medical symptom is selected from polycystic kidney disease and inflammatory bowel.
16. according to the compositions of claim 1, wherein said medical symptom results from chloride ion and the excretory minimizing of water.
17. according to the compositions of claim 16, wherein said medical symptom is a gastroenteropathy.
18. according to the compositions of claim 17, wherein said disease is constipation.
19. according to the compositions of claim 16, wherein said medical symptom is a Cystic fibrosis.
20. compositions according to claim 18, wherein said constipation is following symptom or side effect: human primary gastrointestinal cancers, the BehectShi disease, the neuropathy of elementary or secondary intestinal, the gastrointestinal dysfunction in the parkinson, irritable bowel syndrome, chronic constipation, the bowel dysfunction in the Hirschsprung transports constipation slowly, gastrointestinal dysfunction in the Alzheimer, or the treatment of chronic opioid.
21. magnolol, honokiol, the medical symptom that any or arbitrarily multiple treatment that is combined in preparation claim 1-20 is caused by unusual chloride ion flow in Isoarborinol methyl ether. and the isoimperatorin is or/and regulate the application of the pharmaceutical composition aspect of chloride ion flow and fluid secretion.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/313,772 | 2002-12-06 | ||
| US10/313,772 US6923992B2 (en) | 2001-12-17 | 2002-12-06 | Active compounds of Bao-Ji-Wan for anti-diarrhea and relieving gastrointestinal symptoms |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1506046A true CN1506046A (en) | 2004-06-23 |
| CN100562315C CN100562315C (en) | 2009-11-25 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB031238475A Expired - Fee Related CN100562315C (en) | 2002-12-06 | 2003-05-15 | Be used for diarrhea and the Health pill reactive compound that alleviates gastrointestinal disorder |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN100562315C (en) |
| HK (1) | HK1066460A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100998779B (en) * | 2006-01-12 | 2012-07-04 | 广州王老吉药业股份有限公司 | Traditional Chinese medicine granule for relieving exterior syndrome removing dampness and regulating the stomach and its preparing method |
| CN111419858A (en) * | 2019-01-09 | 2020-07-17 | 中国中医科学院中药研究所 | New use of phenylethanoid glycosides compound magnolin A for improving gastrointestinal function |
-
2003
- 2003-05-15 CN CNB031238475A patent/CN100562315C/en not_active Expired - Fee Related
-
2004
- 2004-11-25 HK HK04109297.7A patent/HK1066460A1/en not_active IP Right Cessation
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100998779B (en) * | 2006-01-12 | 2012-07-04 | 广州王老吉药业股份有限公司 | Traditional Chinese medicine granule for relieving exterior syndrome removing dampness and regulating the stomach and its preparing method |
| CN111419858A (en) * | 2019-01-09 | 2020-07-17 | 中国中医科学院中药研究所 | New use of phenylethanoid glycosides compound magnolin A for improving gastrointestinal function |
Also Published As
| Publication number | Publication date |
|---|---|
| HK1066460A1 (en) | 2005-03-24 |
| CN100562315C (en) | 2009-11-25 |
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