CN101152168A - Isoliquirtigenin capsule for treating gastrospasm - Google Patents
Isoliquirtigenin capsule for treating gastrospasm Download PDFInfo
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- CN101152168A CN101152168A CNA2007100531509A CN200710053150A CN101152168A CN 101152168 A CN101152168 A CN 101152168A CN A2007100531509 A CNA2007100531509 A CN A2007100531509A CN 200710053150 A CN200710053150 A CN 200710053150A CN 101152168 A CN101152168 A CN 101152168A
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Abstract
The invention discloses an isoliquiritigenin capsule used to treat gastrospasm. The isoliquiritigenin capsule is characterized in that the capsule contains isoliquiritigenin, filler and stabilizer, which are proportioned according to a certain proportion. The drug prepared combination has good anti-spasm function to muscle spasticity caused by different stimulators and is capable of dispelling the pain caused by gastrospasm. The formula has reasonable formula, high treatment rate, rapid and good effect, low side effects and low cost.
Description
Technical field
The present invention relates to pharmaceutical field, more specifically relate to a kind of isoliquiritigenin capsule for the treatment of stomach spasm, with isoliquiritigenin (isoliquiritigenin, ISL) prepare the capsule for the treatment of stomach spasm as effective ingredient, this capsule has the effect of good releasing stomach spasm, can effectively alleviate the angina abdominis that stomach spasm causes.
Background technology
The stomach functional disorder disease becomes the modern people of the influence important diseases of quality of life, and its sickness rate is up to 10%-20%, wherein 98% needs of patients Drug therapy.Clinical medicine commonly used is a cholinergic blocking agent, as atropine and hyoscyami class etc., although the clinical efficacy of this class medicine is reliable, but because effect poor selectivity, toxic and side effects is remarkable, as xerostomia, nervous, gerontal patient's urine retention, glaucoma patient acute attack etc., thereby limited their clinical practice.Then maybe should not use the time depend on analgesics when anticholinergic agent is invalid, latter's toxicity has addiction more greatly and often more.Theory of Chinese medical science thinks that the digestive tract spasmic pain belongs to due to stagnation of liver-QI, cold coagulation, food stagnation, stone resistance or worm faint etc. more, and the clinical application principle is to regulate the flow of vital energy.Chinese patent medicine is a lot of on the one hand for this, but often onset is slower, and difficulty is used for emergency case.To this class disease, especially very difficult to gerontal patient, glaucoma patient medication, the cholinergic blocking agent of therapeutic dose often brings out even more serious or painful complication clinically.
In motherland's medical science, Radix Glycyrrhizae is used as medicine with a long history.Record the earliest sees Shennong's Herbal, claim in the book Radix Glycyrrhizae " main vital organs of the human body cold and heat pathogen, hard muscles and bones, longue meat, times strength, incised wound is swollen, detoxifcation, clothes are made light of one's life by commiting suicide and are prolonged life for a long time." in recent years every research also shows, Radix Glycyrrhizae can suppress that animals such as rat, Cavia porcellus are exsomatized or in the activity of body intestinal tube; The liquorice beverage decoct can directly influence the activity of each position smooth muscle of rat isolated stomach; Radix Glycyrrhizae influences the active mechanism of gastrointestinal may be relevant with the secretion that suppresses materials such as 5-HT.The untoward reaction of Radix Glycyrrhizae is few, and the clinical efficacy of active component is remarkable, often has important clinical application value to treating such disease.
Isoliquiritigenin (isoliquiritigenin ISL), is a kind of effective monomer in the Radix Glycyrrhizae, belongs to flavone compound, and chemical constitution is 2 ', 4 ', 4 '-trihydroxy chalcone derivative, and molecular structure is:
Though Radix Glycyrrhizae and extracting solution thereof have spasmolytic effect preferably for pipe smooth muscle, relevant isoliquiritigenin and oral formulations thereof do not appear in the newspapers as yet to the regulating action of pipe smooth muscle motion.
Summary of the invention
The objective of the invention is to be to provide a kind of isoliquiritigenin capsule for the treatment of stomach spasm, this capsule formula is reasonable, treatment rate is high, very little to the human body toxic and side effects, and zest is little, taking convenience.
Technical scheme provided by the invention is that isoliquiritigenin is used to prepare the pharmaceutical composition for the treatment of stomach spasm.
Isoliquiritigenin of the present invention is 2 ', 4 ', and 4 '-trihydroxy chalcone derivative both can chemosynthesis, also direct separation and Extraction from Radix Glycyrrhizae, and also market is on sale.
The present invention is used to isoliquiritigenin to prepare the pharmaceutical composition of treatment or prevention stomach spasm.In order to realize the present invention, by the following technical solutions: with the isoliquiritigenin is effective ingredient, is equipped with pharmaceutically acceptable carrier, can be made into the capsule that is used for the treatment of stomach spasm.
A kind of isoliquiritigenin capsule for the treatment of the pipe smooth muscle spasm, the weight percentage ranges of isoliquiritigenin and various adjuvants is: isoliquiritigenin 10-15%, filler 80-88%, stabilizing agent 1-5%;
A kind of isoliquiritigenin capsule for the treatment of the pipe smooth muscle spasm, the preferred weight percent scope of isoliquiritigenin and various adjuvants is: isoliquiritigenin 12-14%, filler 82-86%, stabilizing agent 2-4%
Described filler is starch, Icing Sugar, pregelatinized Starch, lactose, glucose, microcrystalline Cellulose, calcium carbonate, calcium sulfate, calcium bicarbonate or other pharmaceutically acceptable carriers are wherein a kind of or 2-9 kind or combination in any.
Described stabilizing agent is cyclodextrin clathrate, magnesium stearate, sucrose, mannitol, lactose, glucose, trehalose or other pharmaceutically acceptable carriers a kind of or 2-7 kind or a combination in any wherein;
A kind of isoliquiritigenin capsule for the treatment of the pipe smooth muscle spasm, its preparation method is:
1. make ointment: isoliquiritigenin is mixed with filler, and with 15% ethanol moistening, stirring and evenly mixing is made paste;
2. granulate: the ointment of mixing is crossed 100 order nylon mesh granulate, 60-80 order ferrum sieve granulate is crossed in oven dry below vacuum 70-80 ℃ 1 hour;
3. fill: add the stabilizing agent mixing, encapsulated, every weight is 0.3g.
Advantage of the present invention:
1. isoliquiritigenin both can chemosynthesis, also direct separation and Extraction from Radix Glycyrrhizae, and wide material sources, but also can directly buy from the market.
2. isoliquiritigenin capsule of the present invention can be removed the pipe smooth muscle spasm that different reasons cause effectively, thereby effectively alleviates the angina abdominis that causes owing to stomach spasm, and effective percentage can reach 90-98%.
3. the isoliquiritigenin capsule has no side effect substantially to human body, and drug effect is rapid, and is easy to use, respond well.
4. the present invention adopts conventional oral administered dosage form, technology maturation, and production technology is simple, and is with low cost.
5. the present invention adopts oral administration mode, convenient drug administration, no pain.
Description of drawings
Fig. 1 represents the influence of variable concentrations isoliquiritigenin to stomach sill strip smooth muscle spasm due to the potassium ion.Abscissa is represented the logarithm value of potassium concentration among the figure, and vertical coordinate is represented specimen contraction intensity relative percentage.■ shows the blank group; ▲ show isoliquiritigenin 1.0 * 10
-3The M group; ● show isoliquiritigenin 1.0 * 10
-1The M group.
Compare with the blank group, isoliquiritigenin all can significantly reduce the shrinkage amplitude of stomach sill strip smooth muscle specimen, illustrates that isoliquiritigenin can suppress the rat stomach sill strip smooth muscle spasm that potassium ion causes, thereby alleviates the angina abdominis that is caused by stomach spasm, and its effect is concentration dependent, with 1.0 * 10
-1The effect of M group is the strongest, can adjust its medication dose according to the state of an illness during prompting clinical application.
Fig. 2 represents the influence of variable concentrations isoliquiritigenin to the stomach sill strip smooth muscle spasm due to the barium ions.Abscissa is represented the logarithm value of barium ions concentration among the figure, and vertical coordinate is represented specimen contraction intensity relative percentage.■ shows the blank group; ▲ show isoliquiritigenin 10
-3The M group; ● show isoliquiritigenin 10
-1The M group.
Compare with the blank group, isoliquiritigenin all can significantly reduce the shrinkage amplitude of stomach sill strip smooth muscle specimen, illustrates that isoliquiritigenin can suppress the rat stomach sill strip smooth muscle spasm that barium ions causes, thereby alleviates the angina abdominis that is caused by stomach spasm, and its effect is concentration dependent, with 1.0 * 10
-1The effect of M group is the strongest, can adjust its medication dose according to the state of an illness during prompting clinical application.
Fig. 3 represents the influence of variable concentrations isoliquiritigenin to the stomach sill strip smooth muscle spasm due to the 5-HT.Abscissa is represented the logarithm value of 5-HT concentration among the figure, and vertical coordinate is represented specimen contraction intensity relative percentage.■ shows the blank group; ▲ show isoliquiritigenin 1.0 * 10
-3The M group; shows isoliquiritigenin 10
-2The M group; ● show isoliquiritigenin 1.0 * 10
-1The M group.
Compare with the blank group, isoliquiritigenin all can significantly reduce the shrinkage amplitude of stomach sill strip smooth muscle specimen, illustrates that isoliquiritigenin can suppress the rat stomach sill strip smooth muscle spasm that 5-HT causes, thereby alleviates the angina abdominis that is caused by stomach spasm, and its effect is concentration dependent, with 1.0 * 10
-1The effect of M group is the strongest, can adjust its medication dose according to the state of an illness during prompting clinical application.
Fig. 4 represents the influence of variable concentrations isoliquiritigenin to the spasm of the stomach sill strip smooth muscle due to the practolol.Abscissa is represented the logarithm value of practolol concentration among the figure, and vertical coordinate is represented the relative percentage of the contraction intensity of specimen.■ shows the blank group; ▲ show isoliquiritigenin 1.0 * 10
-3The M group; shows isoliquiritigenin 10
-2The M group; ● show isoliquiritigenin 1.0 * 10
-1The M group.
Compare with the blank group, isoliquiritigenin all can significantly reduce the shrinkage amplitude of stomach sill strip smooth muscle sample, illustrates that isoliquiritigenin can suppress the rat stomach smooth muscle spasm that eraldin causes, thereby alleviates the eilema that is caused by gastrospasm, and its effect is concentration dependent, with 1.0 * 10-1The effect of M group is the strongest, can adjust its medication dose according to the state of an illness during prompting clinical application.
The specific embodiment
Various details embodiment, but content of the present invention is not limited thereto fully.
| Isoliquiritigenin | Filler | Stabilizing agent | |
| Embodiment 1 | 10.0％ | Starch 88.0% | Magnesium stearate 2.0% |
| Embodiment 2 | 11.0％ | Calcium carbonate 88.0% | Trehalose 1.0% |
| Embodiment 3 | 11.5％ | Starch 83.8% | Magnesium stearate 4.7% |
| Embodiment 4 | 12.0％ | Dextrin 86.0% | Glucose 2.0% |
| Embodiment 5 | 12.5％ | Dextrin 84.0% | Trehalose 3.5% |
| Embodiment 6 | 13.0％ | Starch 83.5% | Magnesium stearate 3.5% |
| Embodiment 7 | 13.5％ | Dextrin 82.0% | Magnesium stearate 4.5% |
| Embodiment 8 | 14.0％ | Dextrin 83.0% | Glucose 3.0% |
| Embodiment 9 | 14.5％ | Starch 82.6% | Magnesium stearate 2.9% |
| Embodiment 10 | 15.0％ | Starch 84.0% | Glucose 1.0% |
Described filler is starch, Icing Sugar, pregelatinized Starch, lactose, glucose, microcrystalline Cellulose, calcium carbonate, calcium sulfate, calcium bicarbonate or other pharmaceutically acceptable carriers a kind of or 2-9 kind or a combination in any wherein.
Described stabilizing agent is cyclodextrin clathrate, magnesium stearate, sucrose, mannitol, lactose, glucose, trehalose or other pharmaceutically acceptable carriers a kind of or 2-7 kind or a combination in any wherein;
A kind of isoliquiritigenin capsule for the treatment of stomach spasm, concrete preparation method is as follows:
1. make ointment: isoliquiritigenin is mixed with filler, and with 15% ethanol moistening, stirring and evenly mixing is made paste;
2. granulate: the ointment of mixing is crossed 100 order nylon mesh granulate, 60-80 order ferrum sieve granulate is crossed in oven dry below vacuum 70-80 ℃ 1 hour;
3. fill: add the stabilizing agent mixing, encapsulated, every weight is 0.3g.
Pharmacodynamic experiment
Isoliquiritigenin is to the spasmolysis of rat stomach sill strip smooth muscle
Laboratory animal:
The Sprague-Dawley rat, the SPF level, male, body weight 250～270g is provided by Wuhan University's Experimental Animal Center.The animal credit number is: SYXK (Hubei Province) 2003-0004.
Experimental drug:
Serotonin (5-HT, USA.Sigma) 1.0 * 10
-5-1.0 * 10
-1M, practolol (practolol, Shanghai chemical reagent head factory) 1.0 * 10
-5-1.0 * 10
-1M, isoliquiritigenin (ISL, the non-clinical experiment of Wuhan University's medicine center is synthetic) 1.0 * 10
-3M, 1.0 * 10
-2M, 1.0 * 10
-1M, sodium chloride (NaCl) 136.6 * 10
-3M, calcium chloride (CaCl
2) 1.8 * 10
-9M, sodium bicarbonate (NaHCO
3) 12.0 * 10
-9M, magnesium chloride (MgCl
2) 0.5 * 10
-9M, potassium dihydrogen phosphate (NaH
2PO
4) 0.14mmol/L, glucose (glucose) 5.5 * 10
-9Mmol/L, potassium chloride (KCl) 1.0 * 10
-5-1.0 * 10
-1M, barium chloride (BaCl
2) 1.0 * 10
-5-1.0 * 10
-1M, (reagent Manufacturing Co., Ltd is learned in permanent Xinghua, Tianjin, and experimental drug is analytical pure)
Experimental apparatus:
BL-310 bio signal acquisition system
Tonotransducer (range: 50g)
Magnus' bath (volume: 10ml)
Experimental procedure:
1. the rat fasting was put to death after 24 hours, took out stomach, was placed on behind mesentery that removal is adhered to and the fat and filled O
2(the double 5%CO that contains
2), (form: NaCl 136.6 to be incubated about 37 ℃ krebs solution; KCl 2.7; CaCl
21.8; NaHCO
312.0; MgCl
20.5; NaH
2PO
40.14; Clean its content in the glucose 5.5 (unit: mmol/L)), cut off along the lesser gastric curvature place again (destruction ring muscle), get stomach bottom muscle and make wide 3-5mm, the bar section of long 20mm hangs on hatches 1h (every 15min changes Precerving liquid one time) in the Magnus' bath that contains the 10ml krebs solution, give the tension load of 1g simultaneously.
2. with 3 * 10
-3The carbachol 0.1mL or 3 * 10 of mol/L
-6The 5-HT 0.2mL of mol/L is exciting, and specimen is shunk, when specimen reach shrink maximum after, Precerving liquid is outwelled, and, is made it recover the normally easypro rhythm and pace of moving things that contracts with krebs solution drip washing specimen 3-5 time.
3. make the KCl (1 * 10 that in bath, adds cumulative concentration respectively
-5-1 * 10
-1M), measure the response curve of its contraction intensity to drug level.Drip washing is hatched, and treats that (low dose group concentration was 1.0 * 10 with the Precerving liquid that contains the variable concentrations isoliquiritigenin respectively in advance again after it recovered the normal easypro rhythm and pace of moving things that contracts
-3M; Middle dosage group concentration is 1.0 * 10
-2M; High dose group concentration is 1.0 * 10
-1M) hatch specimen, treat to survey its response curve again after specimen is stablized the KCl of cumulative concentration.
4. make the BaCl that in bath, adds cumulative concentration respectively
2(1 * 10
-5-1 * 10
-1M), measure the response curve of its contraction intensity to drug level.Drip washing is hatched, and treats that (low dose group concentration was 1.0 * 10 with the Precerving liquid that contains the variable concentrations isoliquiritigenin respectively in advance again after it recovered the normal easypro rhythm and pace of moving things that contracts
-3M; Middle dosage group concentration is 1.0 * 10
-2M; High dose group concentration is 1.0 * 10
-1M) hatch specimen, treat to survey its BaCl again after specimen is stablized cumulative concentration
2Response curve.
5. make the 5-HT (1.0 * 10 that in bath, adds cumulative concentration respectively
-5-1.0 * 10
-1M), measure the response curve of its contraction intensity to drug level.Drip washing is hatched, and treats that (low dose group concentration was 1.0 * 10 with the Precerving liquid that contains the variable concentrations isoliquiritigenin respectively in advance again after it recovered the normal easypro rhythm and pace of moving things that contracts
-3M; Middle dosage group concentration is 1.0 * 10
-2M; High dose group concentration is 1.0 * 10
-1M) hatch specimen, treat to survey its response curve again after specimen is stablized the 5-HT of cumulative concentration.
6. make the practolol (1.0 * 10 that in bath, adds cumulative concentration respectively
-5-1 * 10
-1M), measure the response curve of its contraction intensity to drug level.Drip washing is hatched, and treats that (low dose group concentration was 1.0 * 10 with the Precerving liquid that contains the variable concentrations isoliquiritigenin respectively in advance again after it recovered the normal easypro rhythm and pace of moving things that contracts
-3M; Middle dosage group concentration is 1.0 * 10
-2M; High dose group concentration is 1.0 * 10
-1M) hatch specimen, treat to survey its response curve again after specimen is stablized the practolol of cumulative concentration.
Experimental result:
Compare with the blank group (
*P＜0.05, n=6), isoliquiritigenin 1.0 * 10
-3M, 1.0 * 10
-2M, 1.0 * 10
-1The shrinkage amplitude of M group smooth muscle specimen obviously reduces, with 1.0 * 10
-1The effect of M group is the strongest.The variable concentrations isoliquiritigenin hatch the back specimen to the various response curves of convulsion agent that cause shown in Fig. 1-4.
Fig. 1-4 result shows: with the blank group relatively, the isoliquiritigenin of finite concentration scope can both significantly reduce the shrinkage amplitude of the smooth muscle specimen that is caused by inorganic ions such as KCl and 5-HT or Biomedia, and its effect is concentration dependent, with 1.0 * 10
-1The effect of M group is the strongest, shows that isoliquiritigenin can suppress the rat stomach smooth muscle spasm, thereby alleviates the angina abdominis that is caused by stomach spasm.
Conclusion:
Experimental result shows that isoliquiritigenin can effectively alleviate the excess shrinkage of the pipe smooth muscle that a variety of causes causes, effectively alleviates the abdominal colic that is caused by stomach spasm.The mechanism that isoliquiritigenin is regulated the pipe smooth muscle contraction may be because for K
+And Ca
2+The inhibitory action of ion channel and to the blocking effect of Biomedia receptors such as 5-HT.
Claims (9)
1. isoliquiritigenin capsule for the treatment of stomach spasm, it is made by the percentage by weight of following raw material:
Raw material %
Isoliquiritigenin 10-15
Filler 80-88
Stabilizing agent 1-5
Described filler is a kind of or 2-9 kind or the combination in any in starch, Icing Sugar, pregelatinized Starch, lactose, glucose, microcrystalline Cellulose, calcium carbonate, calcium sulfate, the calcium bicarbonate;
Described stabilizing agent is a kind of or 2-7 kind or the combination in any in cyclodextrin clathrate, magnesium stearate, sucrose, mannitol, lactose, glucose, the trehalose;
Its preparation process is: at first isoliquiritigenin is mixed with filler, with 15% ethanol moistening, stirring and evenly mixing is made paste; Secondly the ointment of mixing is crossed 100 order nylon mesh and granulated, 60-80 order ferrum sieve granulate is crossed in oven dry below vacuum 70-80 ℃ 1 hour; Add the stabilizing agent mixing once more, encapsulated.
2. a kind of isoliquiritigenin capsule for the treatment of stomach spasm according to claim 1, it is characterized in that: it is made by following raw materials by weight: isoliquiritigenin 12-14%, filler 82-86%, stabilizing agent 2-4%.
3. a kind of isoliquiritigenin capsule for the treatment of stomach spasm according to claim 1, it is characterized in that: it is made by following raw materials by weight: isoliquiritigenin 11.0%, starch 88.0%, magnesium stearate 1.0%.
4. a kind of isoliquiritigenin capsule for the treatment of stomach spasm according to claim 1, it is characterized in that: it is made by following raw materials by weight: isoliquiritigenin 12.0%, dextrin 86.0%, trehalose 2.0%.
5. a kind of isoliquiritigenin capsule for the treatment of stomach spasm according to claim 1, it is characterized in that: it is made by following raw materials by weight: isoliquiritigenin 12.5%, dextrin 84.0%, glucose 3.5%.
6. a kind of isoliquiritigenin capsule for the treatment of stomach spasm according to claim 1, it is characterized in that: it is made by following raw materials by weight: isoliquiritigenin 13.0%, starch 83.5%, trehalose 3.5%.
7. a kind of isoliquiritigenin capsule for the treatment of stomach spasm according to claim 1, it is characterized in that: it is made by following raw materials by weight: isoliquiritigenin 13.5%, starch 82.0%, magnesium stearate 4.5%.
8. a kind of isoliquiritigenin capsule for the treatment of stomach spasm according to claim 1, it is characterized in that: it is made by following raw materials by weight: isoliquiritigenin 14.0%, starch 83.0%, glucose 3.0%.
9. a kind of isoliquiritigenin capsule for the treatment of stomach spasm according to claim 1, it is characterized in that: it is made by following raw materials by weight: isoliquiritigenin 15.0%, starch 84.0%, glucose 1.0%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100531509A CN101152168A (en) | 2007-09-06 | 2007-09-06 | Isoliquirtigenin capsule for treating gastrospasm |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100531509A CN101152168A (en) | 2007-09-06 | 2007-09-06 | Isoliquirtigenin capsule for treating gastrospasm |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101152168A true CN101152168A (en) | 2008-04-02 |
Family
ID=39254188
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007100531509A Pending CN101152168A (en) | 2007-09-06 | 2007-09-06 | Isoliquirtigenin capsule for treating gastrospasm |
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| Country | Link |
|---|---|
| CN (1) | CN101152168A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107126433A (en) * | 2017-05-18 | 2017-09-05 | 宁夏医科大学 | Isoliquiritigenin is used as the application and pharmaceutical composition prepared in improvement or treatment resisting kinetic fatigue medicine |
| CN109481424A (en) * | 2018-11-08 | 2019-03-19 | 温州医科大学附属第医院 | Isoliquiritigenin, pharmaceutical composition and its application in treatment diabetic nephropathy |
-
2007
- 2007-09-06 CN CNA2007100531509A patent/CN101152168A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107126433A (en) * | 2017-05-18 | 2017-09-05 | 宁夏医科大学 | Isoliquiritigenin is used as the application and pharmaceutical composition prepared in improvement or treatment resisting kinetic fatigue medicine |
| CN109481424A (en) * | 2018-11-08 | 2019-03-19 | 温州医科大学附属第医院 | Isoliquiritigenin, pharmaceutical composition and its application in treatment diabetic nephropathy |
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Open date: 20080402 |