CN101703573A - Chinese medicinal soft capsule for treating gastral cavity pain and preparation method thereof - Google Patents

Abstract

The invention discloses a Chinese medicinal soft capsule for treating gastral cavity pain and a preparation method thereof. The soft capsule is prepared from 75 to 95 weight percent of litsea lancilimba, 5 to 25 weight percent of blumea camphor and appropriate amount of auxiliary materials. The Chinese medicinal soft capsule has the effects of promoting qi circulation and relieving pain, and is mainly used for treating symptoms such as gastral cavity pain, acid regurgitation during belching, tumescence, stethalgia, chest distress, short breath, palpitation and the like which are caused by qi stagnancy and blood stasis. The original stomach analgesic capsules are changed into the soft capsule preparations; and the Chinese medicinal soft capsule has improved stability and curative effect, accurate contents of the medicaments, beautiful appearance, high purity, little administration dosage, high bioavailability, stable quality, good curative effect and good safety.

Description

Chinese medicinal soft capsule of treatment gastralgia and preparation method thereof

Technical field

The present invention relates to a kind of Chinese medicinal soft capsule for the treatment of gastralgia and preparation method thereof, belong to technical field of medicaments.

Background technology

Stomachache claims gastric abscess again, is the illness that pain often takes place based on the nearly pit of the stomach of gastral cavilty place.Alleged " pained ", " epigastric pain " in the successive dynasties document refers to stomachache more.As " element is asked. the hexa-atomic big opinion of just recording " say: and " the sick epigastralgia right below the heart of the people." " medical science main story " say: " ancient prescription nine types of precordial pain ...Detailed its reason, all at gastral cavilty, and the real heart that do not lie in." stomachache is a common clinically symptom, sees acute or chronic gastritis more, stomach, duodenal ulcer disease, the nervus gastrica palace can disease.Also see diseases such as prolapse of gastric mucosa, gastroptosis, pancreatitis, cholecystitis and cholelithiasis.Gastric abscess is commonly encountered diseases and the frequently-occurring disease in clinical, and its sickness rate occupies first of the various diseases, blue or green clinically, in, elderly population all can suffer from this disease.In recent years, owing to work, life stress strengthen, its sickness rate is the trend that increases year by year.Clinical treatment gets up, such as Chinese medical discriminations such as chronic gastritis, acute bleedingerosive gastritis, gastric ulcer companion pylorus partial obstruction, chronic atrophic gastritis, bile reflux gastritis, chronic atrophic gastritis companion polyps is the gastric abscess person, usually obstinate.

The technology of the present invention is to carry out technological improvement on original product XINWEI ZHITONG JIAONANG basis, prescription is made up of Fructus cinnamomi camphorae, Borneolum Syntheticum, former dosage form method for making is Fructus cinnamomi camphorae to be pulverized the back mix with Borneolum Syntheticum, its function cure mainly into " promoting the circulation of QI to relieve pain; be used for the gastralgia of caused by energy stagnation and blood stasis; belch acid regurgitation, distension and chest pain, uncomfortable in chest, breathe hard, cardiopalmus etc. ".Clinical application for many years shows, former dosage form clinical efficacy is good, but have 2 deficiencies: the former dosage form of the first cures mainly fully and explains with traditional Chinese medical science term, in conjunction with what disease of doctor trained in Western medicine explanation treatment, has brought certain limitation for the popularization of this medicine, and clinical practice applies to treat various gastropathy, disease is seen gastralgia, belch acid regurgitation, distension, and coronary heart disease and angina pectoris, disease see chest pain, uncomfortable in chest, breathe hard, cardiopalmus etc.; It two is that former dosage form preparation technology is coarse, and scientific and technological content is not high, all contains a large amount of volatile material in Fructus cinnamomi camphorae and the Borneolum Syntheticum in the present technique simultaneously, adopt common hard capsule, sealing is poor, causes volatile material to lose in a large number, can't ensure drug quality and curative effect.

Summary of the invention

Technical problem to be solved by this invention is to provide a kind of Chinese medicinal soft capsule for the treatment of gastralgia and preparation method thereof, and medicine of the present invention has no side effect, therapeutic effect is good and rapid-action, bioavailability is high, thereby overcomes the deficiencies in the prior art.

Technical scheme of the present invention is as follows: the Chinese medicinal soft capsule of treatment gastralgia, to calculate according to percentage by weight, and it is to add appropriate amount of auxiliary materials by Fructus cinnamomi camphorae 75～95% and Blumeae preparatum Tabellae 5～25% to be prepared into soft capsule.

The Chinese medicinal soft capsule of above-mentioned treatment gastralgia is more preferably according to percentage by weight and calculates, and adds appropriate amount of auxiliary materials by Fructus cinnamomi camphorae 85.7% and Blumeae preparatum Tabellae 14.3% and is prepared into soft capsule.

The Chinese medicinal soft capsule of aforesaid treatment gastralgia prepares like this: take by weighing Fructus cinnamomi camphorae and Blumeae preparatum Tabellae; Get Fructus cinnamomi camphorae with steam distillation or supercritical CO ₂Extract volatile oil, standby; Get oleaginous base and suspending agent, heating and melting, be chilled to room temperature after, add said extracted volatile oil and Blumeae preparatum Tabellae mix homogeneously, make soft capsule.

Say that accurately the Chinese medicinal soft capsule of above-mentioned treatment gastralgia prepares like this: take by weighing Fructus cinnamomi camphorae and Blumeae preparatum Tabellae; Get Fructus cinnamomi camphorae, add 3 times of water gagings, soak 3h, distillation extraction 8h; Get volatile oil, standby; Get soybean oil and Cera Flava is an amount of, heating and melting, be chilled to room temperature after, add above-mentioned volatile oil and Blumeae preparatum Tabellae mix homogeneously, colloid mill ground 15 minutes, was pressed into soft capsule.

Say that accurately the Chinese medicinal soft capsule of above-mentioned treatment gastralgia can also prepare like this: take by weighing Fructus cinnamomi camphorae and Blumeae preparatum Tabellae; Get Blumeae preparatum Tabellae, pulverize, cross 120 mesh sieves, standby; Get Fructus cinnamomi camphorae, supercritical CO ₂Extraction volatile oil, standby; Get soybean oil and Cera Flava is an amount of, heating and melting, be chilled to room temperature after, add above-mentioned volatile oil and Blumeae preparatum Tabellae mix homogeneously, colloid mill ground 15 minutes, was pressed into soft capsule.

The preparation method of the Chinese medicinal soft capsule of aforesaid treatment gastralgia can also be such: take by weighing Fructus cinnamomi camphorae and Blumeae preparatum Tabellae; Get Fructus cinnamomi camphorae, with steam distillation or supercritical CO ₂Extract volatile oil, standby; Water liquid after the distillation filters, and device is collected in addition, and is standby; The medicinal residues that extract behind the volatile oil decoct with water 1～3 time, and each 0.5～2 hour, collecting decoction filtered, and merge with water liquid after the distillation, are evaporated to the thick paste of 60 ℃ of relative densities 1.30～1.35, and drying is pulverized, and crosses 100 orders with top sieve, extract powder, standby; Get oleaginous base and suspending agent, heating and melting, be chilled to room temperature after, add said extracted volatile oil and Blumeae preparatum Tabellae mix homogeneously, add above-mentioned extract powder, mix homogeneously is made soft capsule.

Say that accurately the preparation method of the Chinese medicinal soft capsule of above-mentioned treatment gastralgia is such: take by weighing Fructus cinnamomi camphorae and Blumeae preparatum Tabellae; Get Blumeae preparatum Tabellae, pulverize, cross 120 mesh sieves, standby; Get Fructus cinnamomi camphorae, add 3 times of water gagings, soak 3h, distillation extraction 8 hours is got volatile oil, and is standby; Water liquid after the distillation filters, and device is collected in addition, and is standby; Medicinal residues behind the extraction volatile oil add 8 times of water gagings and decoct 1 time, each 1.5 hours, collecting decoction filters, with the water liquid merging after the distillation, under 65～75 ℃, be evaporated to the thick paste of 60 ℃ of relative densities 1.30～1.35, at 60～70 ℃ of following drying under reduced pressure, pulverize, cross 120 mesh sieves, get extract powder, standby; Get soybean oil and Cera Flava is an amount of, heating and melting, be chilled to room temperature after, add said extracted volatile oil and Blumeae preparatum Tabellae mix homogeneously, add above-mentioned extract powder, mix homogeneously, colloid mill ground 15 minutes, was pressed into soft capsule.

Say that accurately the preparation method of the Chinese medicinal soft capsule of above-mentioned treatment gastralgia can also be like this: take by weighing Fructus cinnamomi camphorae and Blumeae preparatum Tabellae; Get Blumeae preparatum Tabellae, pulverize, cross 120 mesh sieves, standby; Get the Fructus cinnamomi camphorae supercritical CO ₂Extraction volatile oil, standby; Medicinal residues behind the extraction volatile oil add 8 times of water gagings and decoct 2 times, and each 1.5 hours, collecting decoction filtered, under 65～75 ℃, be evaporated to the thick paste of 60 ℃ of relative densities 1.30～1.35,, pulverize at 60～70 ℃ of following drying under reduced pressure, cross 120 mesh sieves, get extract powder, standby; Get soybean oil and Cera Flava is an amount of, heating and melting, be chilled to room temperature after, add above-mentioned volatile oil and Blumeae preparatum Tabellae mix homogeneously, add above-mentioned extract powder, mix homogeneously, colloid mill ground 15 minutes, was pressed into soft capsule.

Medicine side of the present invention separates: the treatment of stomachache is a basic principle with the regulating qi-flowing for harmonizing stomach pain relieving.Be intended to dredge mechanism of qi, recover the stomach internal organs and along logical property of falling, general rule not bitterly, thereby reach aim of alleviating pain.The true person that has a stomachache controls based on eliminating evil, according to cold coagulation, food stop, the stagnation of QI, hot and suffocating, blood stasis, damp and hot difference, respectively with warming stomach for dispelling cold, dyspepsia and intestinal stasis relieving, depressed liver-energy dispersing and QI regulating, the stomach function regulating that expels the heat-evil, blood circulation promoting and blood stasis dispelling, all methods of clearing away heat and eliminating dampness; Belong to empty person, control setting upright, different according to deficiency and coldness, the deficiency of YIN used the method for warming middle-JIAO QI invigorating, yin nourishing stomach reinforcing respectively.The deficiency and excess and the person of opinion, then the method for strengthening vital QI to eliminate pathogenic factors is held concurrently and is used it.We's institute main symptom type is the gastralgia of caused by energy stagnation and blood stasis, and it is main controlling in promoting the circulation of QI to relieve pain, is principal agent with the Fructus cinnamomi camphorae in the side, and hot in nature, it is peppery to distinguish the flavor of; GUIXIN, stomach warp; Merit is at cold expelling, circulation of qi promoting, pain relieving; Be equipped with Blumeae preparatum Tabellae, be ministerial drug, hot, bitter, be slightly cold.GUIXIN, spleen, lung meridian.Has the refreshment of having one's ideas straightened out, the clearing away heat to alleviate pain effect.Two medicines share, and play the merit of promoting the circulation of QI to relieve pain altogether, to the gastralgia of caused by energy stagnation and blood stasis, the belch acid regurgitation, distension and chest pain, uncomfortable in chest, breathe hard, cardiopalmus etc. has good effect.

Function of the present invention cures mainly: promoting the circulation of QI to relieve pain.The gastralgia that is used for caused by energy stagnation and blood stasis, the belch acid regurgitation, distension and chest pain, uncomfortable in chest, breathe hard, cardiopalmus etc.

The present invention changes the original product XINWEI ZHITONG JIAONANG into soft capsule preparation, following superiority is arranged: 1. improve product stability: with gelatin system epithelium, air-tightness is strong, capsule intensity and film barrier property height, the gelatin epithelium surpasses polyethylene film more than 30 times to the oxygen barrier property, and is highly stable to oxygen in the air, can prevent the air oxidation moisture absorption, guarantee that simultaneously volatile material is difficult for loss, but the content stable for extended periods of time; 2. content is accurate: mostly soft capsule is medicine dissolution, suspendible, is emulsified in the solvent, is filled in the capsule as content after making its solution that becomes uniformity, and every capsules contained drug error is little; 3. good looking appearance: the color of film, capsule, transparency, glossiness all can freely be selected, and compare with other goods, and gloss appearance is good; 4. improved the product curative effect, through animal pharmacodynamics test and clinical trial, curative effect has and significantly improves.

In order to verify that medicine of the present invention has excellent curative, the applicant has carried out series of experimental research, and is specific as follows:

One, craft screening and preliminary comparative efficacy test

1, process choice: get big fruit Jiang Zi, it is standby to extract volatile oil; Medicinal residues after the extraction are divided into 3 parts, a water carries, concentrates, dry, pulverize to such an extent that water extract is standby; A with 60% alcohol extraction, concentrate, drying, pulverize to such an extent that ethanol extract is standby.

2, drug effect prerun sample preparation: (1) heart stomach and alleviating pain soft capsule I number: volatile oil+Blumeae preparatum Tabellae+substrate; (2) heart stomach and alleviating pain soft capsule is II number: volatile oil+water extract+Blumeae preparatum Tabellae+substrate; (3) heart stomach and alleviating pain soft capsule is III number: volatile oil+ethanol extract+Blumeae preparatum Tabellae+substrate.

3, this product heart stomach and alleviating pain soft capsule pharmacodynamics prerun test brief summary

(1) is subjected to the reagent thing: XINWEI ZHITONG JIAONANG (being called for short former dosage form down), this product heart stomach and alleviating pain soft capsule I number (being called for short heart I down), this product heart stomach and alleviating pain soft capsule II number (being called for short heart II down), this product heart stomach and alleviating pain soft capsule III number (being called for short heart III down), excipient: soybean oil.Face with preceding and prepare with soybean oil.

(2) isoproterenol is caused the hypoxia endurance test of mice: with the grouping of mice according to the form below, successive administration 7 days.1h after the last administration, lumbar injection isoprenaline (15mg/kg) is put in the wide mouthed bottle that the people fills the 10g sodica calx record death time respectively behind the 15min.Carry out 3 experiments altogether, the results are shown in Table 1:

Table 1

Annotate: * compares * p＜0.05 with model group.

For the first time adopt clinical equivalent dosage to test DeGrain.For the second time test DeGrain with 2 times of clinical equivalent dosage.Consider the difference of body weight and sex for the third time, adopt the unisexuality thing of not moving, body weight difference is no more than the male mice of 2g and tests, and the heart-II can more significantly prolong death time of animal as a result.Compare with former dosage form, though this product heart-II no difference of science of statistics, it is more obvious than former dosage form that it prolongs death time of animal effect.

(3) to the influence of rat pipe film injury due to the ethanol: rat is divided into 6 groups, by the group administration, once a day, one week of successive administration. before the last administration with hungry 24 hours of animal, freely drink water, prohibit water before the beginning administration. only do not give dehydrated alcohol as model group to distilled water. model control group gavages the equal-volume distilled water, the administration group respectively to rat oral gavage give XINWEI ZHITONG JIAONANG (4 samples) after .1 hour each group all only irritate modeling under the stomach with dehydrated alcohol 1.0ml/. after giving damaging material, put to death animal in 1 hour. the ligation pylorus, emit ligation cardia behind the gastric content by cardia, take out stomach, be placed on 10% formaldehyde in fix more than 10 minutes, cut off coat of the stomach along greater gastric curvature, observe the gastric mucosa situation. score according to lesion degree: contrafluxion is rubescent to be 1 minute, petechial hemorrhage or erosion respectively are 2 minutes, rotten to the corn 1 place of wire is 3 minutes, and the total back is as ulcer index and calculate ulcer inhibition rate. ulcer inhibition rate (%)=(matched group ulcer index experimental group ulcer index)/matched group ulcer index * 100%. the results are shown in Table 2:

Table 2

Group	Dosage (g/kg)	Number of animals (only)	The mucosa injury mark	Ulcer inhibition rate (%)
					Blank model	??/	??8	??23.13±12.33
Former dosage form	??0.5	??9	??7.00±3.64**	??69.73
					The heart-I	??0.5	??9	??4.67±2.40**??△	??79.82
The heart-II	??0.5	??9	??4.78±3.31**??△	??79.34
					The heart-III	??0.5	??9	??6.13±2.30**	??73.51
Soybean oil	??/	??8	??11.25±7.36**	??51.35

Annotate: * compares * * p＜0.01 with model group.△ compares △ p＜0.05 with soybean oil.

Because sample adopts the soybean oil dissolving; and the bibliographical information soybean oil has the certain protection effect to the gastric mucosa injury due to the ethanol; so increase a blank group, the result judges whether successful and blank group relatively sees whether sample has effect then to compare with soybean oil to the modeling type.Each sample mucosa injury mark and model group relatively have notable difference, and modeling success is described, and by with the Semen sojae atricolor line of oils relatively, the heart-I, the heart-II can obviously alleviate the gastric mucosa injury due to the ethanol.Compare with former dosage form, this product heart-I, though the heart-II no difference of science of statistics, its gastric mucosa injury effect that alleviates due to the ethanol is more obvious than former dosage form

Conclusion: the experimental result of the influence of rat pipe film injury sees that we think that the heart-II has apparent in view effect in three candidate's dosage forms due to comprehensive hypoxia endurance test and the ethanol.

4, preliminary extraction process is confirmed: by drug effect prerun test knot, medicine of the present invention intends adopting Fructus cinnamomi camphorae with steam distillation or supercritical CO ₂Extract volatile oil, get oleaginous base and suspending agent, heating and melting, be chilled to room temperature after, add said extracted volatile oil and Blumeae preparatum Tabellae mix homogeneously, make soft capsule.Or weighting raw materials material Fructus cinnamomi camphorae is with steam distillation or supercritical CO ₂Extract volatile oil, standby; Water liquid after the distillation filters, and device is collected in addition, and is standby; Extract medicinal residues water behind the volatile oil carry, concentrate, dry, pulverize to such an extent that medicated powder is standby. get oleaginous base and suspending agent, heating and melting, be chilled to room temperature after, adding said extracted volatile oil, Blumeae preparatum Tabellae mix homogeneously add above-mentioned medicated powder, mix homogeneously is made soft capsule.

Two, soft capsule preparation technical study

(1) Study on Preparation 1

1, preparation technology

1.1 prescription: Fructus cinnamomi camphorae 300g, Blumeae preparatum Tabellae 50g.

1.2 method for making: get Blumeae preparatum Tabellae 50g, pulverize, cross 120 mesh sieves, standby; Get Fructus cinnamomi camphorae and add 3 times of water gagings, soak 3h, distillation extraction 8 hours; Get volatile oil, standby; Get soybean oil 316g, Cera Flava 16g, heating and melting, be chilled to room temperature after, add volatile oil and Blumeae preparatum Tabellae 50g mix homogeneously, colloid mill ground 15 minutes, was pressed into 1000 soft capsules, promptly.

2, technical study

2.1 dosage form selection foundation: original product XINWEI ZHITONG JIAONANG, prescription is made up of Fructus cinnamomi camphorae, Borneolum Syntheticum, former dosage form method for making is Fructus cinnamomi camphorae to be pulverized the back mix with Blumeae preparatum Tabellae, its function cure mainly into " promoting the circulation of QI to relieve pain; be used for the gastralgia of caused by energy stagnation and blood stasis; belch acid regurgitation, distension and chest pain, uncomfortable in chest, breathe hard, cardiopalmus etc. ".Clinical application for many years shows, former dosage form clinical efficacy is good, but have 2 deficiencies: the former dosage form of the first cures mainly fully and explains with traditional Chinese medical science term, in conjunction with what disease of doctor trained in Western medicine explanation treatment, has brought certain limitation for the popularization of this medicine, and clinical practice applies to treat various gastropathy, disease is seen gastralgia, belch acid regurgitation, distension, and coronary heart disease and angina pectoris, disease see chest pain, uncomfortable in chest, breathe hard, cardiopalmus etc.; It two is that former dosage form preparation technology is coarse, the scientific and technological content deficiency.The present invention changes it into soft capsule, following superiority is arranged: 1. good stability: with gelatin system epithelium, air-tightness is strong, capsule intensity and film barrier property height, the gelatin epithelium surpasses polyethylene film more than 30 times to the oxygen barrier property, highly stable to oxygen in the air, can prevent the air oxidation moisture absorption, but the content stable for extended periods of time; 2. content is accurate: mostly soft capsule is medicine dissolution, suspendible, is emulsified in the solvent, is filled in the capsule as content after making its solution that becomes uniformity, and every capsules contained drug error is little; 3. good looking appearance: the color of film, capsule, transparency, glossiness all can freely be selected, and compare with other goods, and gloss appearance is good.

2.2 medical material is identified and pre-treatment

Fructus cinnamomi camphorae: this product is the dry fruit of canella Cinnamomum Migao H.W.Li. Cinnamomum migao H.W.Li.Through identifying, this product meets " Guizhou Province's Chinese crude drug, national quality of medicinal material standard " version " Fructus cinnamomi camphorae " following every regulation in 2003.

Blumeae preparatum Tabellae (left-handed Borneolum Syntheticum): this product is the highly finished product of sublimate of the leaf of feverfew Herba Blumeae Balsamiferae Blumea balsamifera (L.) DC..Main component is left-handed Borneolum Syntheticum (L-BORNEOLUM).Through identifying, this product meets " Guizhou Province's Chinese crude drug, national quality of medicinal material standard " version " Blumeae preparatum Tabellae " following every regulation in 2003.

2.3 process route is determined

2.3.1 former dosage form related data: [method for making] above two flavor medical materials, pulverize separately becomes fine powder, adds starch, and mixing incapsulates, promptly.[function with cure mainly] Seedling doctor: lotus China fir Zhang is penetrated, and resembles for stupid retaining: pendulum dashes and repaiies, and the sheet point covers.The traditional Chinese medical science: promoting the circulation of QI to relieve pain.The gastralgia that is used for caused by energy stagnation and blood stasis, the belch acid regurgitation, distension and chest pain, uncomfortable in chest, breathe hard, cardiopalmus etc.[usage and consumption] is oral, one time 2,3 times on the one, 7 days is a course of treatment; Take in ante cibum or the meal.

2.3.2 analyzing and change the dosage form process route, former dosage form process rationality determines

Among the former dosage form preparation technology, Fructus cinnamomi camphorae, Borneolum Syntheticum two flavor medical materials, pulverize separately becomes fine powder, adds starch, and mixing incapsulates, promptly.

Modern study shows: Fructus cinnamomi camphorae oil can relax exsomatize normal organ smooth muscle and histamine or acetylcholine, histamine and or acetylcholine cause the tracheal smooth muscle of convulsion; And can be a visceral smooth muscle relaxant to anti-depressant effects of intestinal smooth muscle such as anti-acetylcholine, histamine and BaC12; The effect of myocardial oxygen consumption be can reduce, isolated heart coronary flow, decreased heart rate increased; The Electrocardiographic variation of guinea pig myocardium ischemia due to the antagonism pituitrin can be used for cardiovascular disease such as clinical prevention coronary heart disease, angina pectoris; Have certain analgesic activity simultaneously.

The preparations shaping part then adds appropriate amount of auxiliary materials by test, pelleting, and typical process flow is:

Get Fructus cinnamomi camphorae → extraction volatile oil → adding Blumeae preparatum Tabellae mixing → pelleting → typing → drying → finished product.

2.4 volatile oil Study on extraction

(1) steam distillation

1. the preferred extraction process of orthogonal test: take by weighing Fructus cinnamomi camphorae 50.0g respectively, extract volatile oil, with 1,8 one content by foline in the volatile oil is index, in conjunction with the principal element that influences this medicinal material extract efficient, investigate the medical material amount of water, soak time, extraction time 3 factors influence, consider to produce actual simultaneously, get 3 levels, select a L for use ₉(3 ⁴) orthogonal table arrangement test, result and analysis in table 3-5.

2. result of the test: the result shows, amount of water, and soak time extracts in the volatile oil 1,8 one to steam distillation has appreciable impact by foline content, and behind the distillation 8h, the time does not make significant difference to extraction.According to analysis result, consider to produce reality simultaneously, determine that best vapor distillation technology is A ₂B ₃C ₁, promptly add 3 times of water gagings, soak 3h, vapor distillation 8h.

Table 3 steam distillation experimental factor level

Table 4 steam distillation L ₉(3 ⁴) orthogonal experiments

The variance analysis of table 5 steam distillation

Annotate: F _0.05(2,2)=19.00

(2) supercritical CO ₂Extraction

Supercritical CO ₂In the extraction Fructus cinnamomi camphorae volatile oil technology, owing to influence the principal element of medical material extraction be: extracting pressure, extraction temperature, CO ₂Flow, extraction time 4 factors, so select uniform Design U for use ₅(5 ⁴) table, get 5 level arrangement tests, see Table 68.The 50.0g that at every turn feeds intake, its granularity is packed into and is extracted in the pond less than 1mm, the pairing factor level extraction of according to the form below volatile oil, parsing pressure is 5MP _a, resolution temperature is 41 ℃.Volatile oil is isolated with freezing method in the extraction back.

Table 6 uniform Design factor level

Table 7U ₅(5 ⁴) Uniform Design result

1,8 one press the defeated people's computer of foline content value with what respectively test the corresponding value of variable and each correspondence in the uniform Design scheme, carry out 2 order polynomials and progressively return, regression equation (factor is selected into and rejects threshold value and all be taken as

3) Y=-5.4028+0.92039A-0.02127A ²+ 0.01855BC, r 2 0.99860.

The variance analysis of table 8 uniform Design

The desired orientation of comprehensive Y and production are actual, carry out excellent A on computers with GLP algorithm (Good lattice point) and program JSYSJ ₃B ₅C ₅D ₃, i.e. extracting pressure 20MP _a, 50 ℃ of extraction temperature, CO ₂Flow velocity 3.0m ³.h ^-1, extraction time 90min.(the extraction time does not make significant difference to extraction, can determine according to reality).

Comprehensive two kinds of technologies, the result of the test there was no significant difference is in conjunction with applicant's production equipment, so intend adopting steam distillation to prepare this product volatile oil.

2.5 preparation process research

2.5.1 preparation prescription research

(1) disperse medium is selected: the disperse medium of soft capsule is generally polyvinyl compound or lipoid material.Though Polyethylene Glycol commonly used is widely used, but because this product principal agent composition is fat-soluble composition, and Polyethylene Glycol is a water-soluble base, according to the similar principle that mixes, so the disperse medium of this product is preferably selected lipoid material for use, is disperse medium in recent years with the vegetable oil, Cera Flava is that the method that suspending agent prepares the suspension type content has obtained using widely, the stability of this technology has also obtained widely approval, thus this experiment with this method as the content preparation method.

(2) the preferred research data of Cera Flava consumption shows in the disperse medium, in the disperse medium that is prepared into soybean oil and Cera Flava, mellisic consumption is generally 2%～5%, and in conjunction with this product extract powder character, we have done following investigation to mellisic concrete usage ratio in this product disperse medium: the according to the form below ratio is got Cera Flava and soybean oil, behind 80 ℃ of heating and meltings, be chilled to room temperature, add extract powder, grind evenly with colloid mill, observe its state, under room temperature, place and observed again in 2 weeks.The results are shown in Table 9.

The Cera Flava consumption is investigated in table 9 disperse medium

Result of the test explanation, it is slightly poor to add the content flowability that 3% Cera Flava is prepared in the soybean oil, is uniformly dispersed but lamination slightly, but under the equal conditions, to make the content flowability slightly poor though add 4% Cera Flava, do not have lamination, is Cera Flava consumption parameter in the disperse medium so select it.

(3) consumption of the preferred disperse medium of disperse medium consumption directly has influence on the dose and the content uniformity of soft capsule: ratio is low excessively, and then content uniformity is big; Ratio is excessive, and then consumption increases, the inconvenience of taking medicine.Therefore need the consumption of disperse medium is investigated, thus the optimum amount of definite disperse medium.By " the Cera Flava consumption is preferred in the disperse medium " test as can be known, when the usage ratio of extract and disperse medium (promptly containing 5% mellisic Semen sojae atricolor hot-melt object) is 1: 3, though it is good to be prepared into the stability of content, but flowability is slightly poor, therefore, we suitably increase the disperse medium consumption on this basis, and have carried out the investigation of 3 levels: the ratio of extract powder and disperse medium was respectively 1: 3,1: 4 and 1: 5.The results are shown in Table 10.

Table 10 disperse medium consumption is investigated

Result of the test shows, when adding 3 parts of disperse medium in 1 part of extract powder, it is less than normal to make the content flowability, when adding 5 parts of disperse medium, it is bigger than normal to make the content flowability, by contrast, the content flowability was moderate when extract powder and disperse medium were pressed 1: 4 mixed, and can determine to select this ratio is disperse medium consumption in this product.

The every prescription Blumeae preparatum Tabellae of this product 50g, Fructus cinnamomi camphorae volatile oil 18g, adding 4 times of amount disperse medium (promptly adding disperse medium 272g) back total amount is 340g.Consider and add to help batching and the calculating of finished product loading amount into the dispensed in small quantity medium, and the stability of content is not had influence, therefore, we are adjusted into 332g with every prescription disperse medium consumption, and promptly adding disperse medium adjustment total amount is 400g.

(4) rubber is write out a prescription preferably according to the literature, and the ratio of gelatin, G ﹠ W was generally 1: 0.3～0.5: 1 in the soft capsule shell.The fixing ratio of gelatin and water changes the ratio of glycerol, makes rubber rate of dissolution indicator with lemon yellow, is that index is investigated the glycerol addition with the dissolution time of rubber.

1. the rubber preparation is measured gelatin granule and glycerol mixing in prescription ratio in the table 11, soak 36h in the water, 70 ℃ of heating down make it dissolving (in order to make the shading and anticorrosion of rubber energy, adding 2 ‰ titanium dioxides and 1 ‰ mud moor gold ethyl esters respectively), behind the vacuum degassing bubble, fully stir, evenly be laid on (the about 2mm of thickness) on the glass plate, put 25 ℃ of dryings 2 hours, blade cuts into the rubber piece of 2cm * 2cm, and is standby.

Table 11 rubber prescription ratio

2. the rubber rate of dissolution is measured precision to get above-mentioned each rubber an amount of, by " two appendix dissolution methods of Chinese pharmacopoeia version in 2000 transfer basket method is measured, with the 500ml distilled water is dissolution medium, and temperature is 37 ± 0.5 ℃, and rotating speed is 30rpm, after waiting not have obvious rubber granule, per minute sampling 1 time, the 5ml that at every turn takes a sample (and add the equivalent distilled water replenish) is until dissolving fully, measure absorbance in wavelength 427nm place, dissolve required time fully to record rubber.Table 12 as a result.

Table 12 rubber rate of dissolution measurement result

Prescription rubber heavy (g) dissolves required time (min) rate of dissolution (min/g) fully

1?????????1.821????????27????????????????????????14.8

2?????????1.674????????26????????????????????????15.5

3?????????1.508????????24????????????????????????15.9

3. the rubber study on the stability is preserved above-mentioned 1～No. 3 prescription sample 30 days 75% time at 25 ℃ of temperature, relative humidity, and the same method is surveyed every required time of gram rubber dissolving of various kinds, the results are shown in Table 13

The different prescription of table 13 rubber solubility property stability is examined

2., 3. result of the test shows, different prescription rubber can both dissolve in 30 minutes fully, explanation is all better with the soft capsule shell dissolubility that these prescriptions make, under the gelatin condition identical with the water yield, 1, the solubility property of No. 2 prescription rubber is more stable, be optional No. 1 prescription, the i.e. gelatin of saving production cost: glycerol: water=1: 0.3: 1.

2.5.2 preparations shaping technical study

(1) content of the selection soft capsule of contents mixed time is wanted sufficient mix homogeneously, otherwise not finely dispersed content agglomerate easily stops up the pellet press shower nozzle in pressing process, influence the accuracy of medicine loading amount, and capsule layering easily in put procedure, stability of drug influenced.General mixing apparatus adopts colloid mill or dispersing emulsification machine.In conjunction with pharmaceutical factory reality, we adopt the colloid mill polishing, and the mill spacing is 5um, have compared the situation of different milling time materials.The results are shown in Table 14.

Table 14 incorporation time the selection result of the test

By above result as can be known, with the colloid mill polishing, grind in 10 minutes and just can reach content feel exquisiteness, the mixing of materials effect of uniform.So determine to grind 10 minutes with colloid mill.

(2) the rubber solidification temperature is selected press the rubber prescription and is prepared glue, make rubber after, be divided into 3 parts, respectively at 10 ℃, 4 ℃, cool off 10min under 0 ℃ of three kinds of temperature.All, observe rubber character and press the dissolubility that preceding method method is measured various kinds rubber, the results are shown in Table 15 in 25 ℃ of following balances of room temperature.

Table 15 rubber solidification temperature is investigated

Result of the test shows that the dissolubility of rubber increases along with the reduction of rubber cooling curing temperature.Water freezing in rubber below 0 ℃ and to cause rubber loose porous, though be beneficial to dissolving, unfavorable for capsular sealing, easy oil impregnate; 10 ℃ of cooling curing rubber are too soft, and poor plasticity selects 4 ℃ of cooling curings to be advisable by contrast.

(3) in the pressing process that is chosen in soft capsule of sprinkler body temperature, the sprinkler body temperature is the key factor that influences soft capsule content uniformity and yield rate.The sprinkler body temperature is low excessively, and the capsule pressing is bad, leakage easily; The sprinkler body temperature is too high, can influence the outward appearance of soft capsule, is prone to special-shaped ball.Investigate the pressing situation and the yield rate of soft capsule under the different temperatures for this reason, the results are shown in Table 16.

The selection result of the test of table 16 sprinkler body temperature

As seen from the experiment, the sprinkler body temperature should be controlled at 42～44 ℃ and is advisable.

(4) setting and drying process condition are selected

1. the selection of soft capsule setting temperature is got no-set soft capsule respectively 15 ℃, 20 ℃, 25 ℃ setting (rule of thumb, envionmental humidity is controlled at about 30% during setting) down, is that index is carried out preferably setting temperature with fixing time, special-shaped ball rate.The results are shown in Table 17.

Table 17 soft capsule shell setting temperature selection result table

From result of the test as can be known, fixing time shortens along with increasing of setting temperature, but temperature is high more, abnormity ball rate also increases thereupon, is unfavorable for the soft capsule shell setting, by contrast, it is short that setting has the time under 20 ℃, and the low advantage of special-shaped ball rate is a setting temperature so select this temperature.

2. the process conditions compacting soft capsule that optimizes is investigated in the selection of soft capsule baking temperature by above-mentioned technology, after the setting, oil stain with 95% ethanol flush away softgel shell surface, be divided into 3 parts, extremely neither too hard, nor too soft 20 ℃, 25 ℃, 30 ℃ down dry (relative humidity is 30%) respectively, drying time also measured disintegration time in record.The results are shown in Table 18.

Table 18 soft capsule shell setting temperature selection result table

Result of the test shows that shorten along with increasing of temperature drying time, but disintegration time slightly increases along with increasing of temperature, 30 ℃ of increasing degrees of disintegration time when dry are bigger, by contrast, 25 ℃ of following drying effects are good, are the soft capsule baking temperature so select this temperature.

3, soft capsule loading amount and dose are determined

According to recipe quantity and Study on Preparation data computation this product loading amount and dose.

(1) loading amount is determined: Fructus cinnamomi camphorae 300g in this product prescription, and the volatile oil extraction ratio is 6%, promptly every prescription is prepared into the about 18g of volatile oil, Blumeae preparatum Tabellae 50g, adding disperse medium (containing 4% mellisic Semen sojae atricolor hot-melt object) to total amount is 400g.Full side is made 1000, and then every loading amount is 0.4g.

(2) dose is determined: the full side of former XINWEI ZHITONG JIAONANG is 175g altogether, makes 1000, and every contains crude drug 0.175g, takes 2 at every turn, is equivalent to take crude drug 0.35g.After dosage form changed, every of this product heart stomach and alleviating pain soft capsule was equivalent to take crude drug 0.35g, therefore, promptly each 1, every day 3 times.

(2) Study on Preparation 2

1, preparation technology

1.1 prescription is with Study on Preparation 1

1.2 method for making is got Blumeae preparatum Tabellae 50g, pulverizes, and crosses 120 mesh sieves, and is standby; Get Fructus cinnamomi camphorae and add 3 times of water gagings, soak 3h, distillation extraction 8 hours is got volatile oil, and is standby; Water liquid after the distillation filters, and device is collected in addition, and is standby; Medicinal residues behind the extraction volatile oil add 8 times of water gagings and decoct 1 time, and each 1.5 hours, collecting decoction, filter, merge with above-mentioned water liquid, concentrating under reduced pressure (65～75 ℃) is to the thick paste of relative density 1.30～1.35 (60 ℃), drying under reduced pressure (60～70 ℃) is pulverized, and crosses 120 mesh sieves. get soybean oil 280g, Cera Flava 20g, heating and melting, be chilled to room temperature after, add volatile oil, Blumeae preparatum Tabellae mix homogeneously, admix extract powder, mix homogeneously, colloid mill ground 15 minutes, was pressed into 1000 soft capsules, promptly.

2, Study on Preparation

2.1 the dosage form selection foundation is with Study on Preparation 1

2.2 medical material evaluation and pre-treatment are with Study on Preparation 1

2.3 process route is determined

2.3.1 former dosage form related data is with Study on Preparation 1

2.3.2 analyzing and change the dosage form process route, former dosage form process rationality determines

Among the former dosage form preparation technology, Fructus cinnamomi camphorae, Borneolum Syntheticum two flavor medical materials, pulverize separately becomes fine powder, adds starch, and mixing incapsulates, promptly

Modern study shows: Fructus cinnamomi camphorae oil can relax exsomatize normal organ smooth muscle and histamine or acetylcholine, histamine and or acetylcholine cause the tracheal smooth muscle of convulsion; And can be a visceral smooth muscle relaxant to anti-depressant effects of intestinal smooth muscle such as anti-acetylcholine, histamine and BaC12; The effect of myocardial oxygen consumption be can reduce, isolated heart coronary flow, decreased heart rate increased; The Electrocardiographic variation of guinea pig myocardium ischemia due to the antagonism pituitrin can be used for cardiovascular disease such as clinical prevention coronary heart disease, angina pectoris; Has certain analgesic activity simultaneously.

The preparations shaping part then adds disperse medium by test, pelleting, and typical process flow is:

Get Fructus cinnamomi camphorae and extract the pulverizing of concentrating under reduced pressure drying under reduced pressure

Add volatile oil, Blumeae preparatum Tabellae and the auxiliary materials and mixing pelleting dry finished product of finalizing the design.

2.4 medical material volatile oil Study on extraction is with Study on Preparation 1

2.5 decocting process research

2.5.1 factor level is established the factor of influence decoction and is mainly contained the following aspects: amount of water, decocting time, decoction number of times etc.Therefore we have carried out the quadrature investigation of 3 factors, 3 levels to these three principal elements, with preferred optimal processing parameter.The factor level table of orthogonal test sees Table 19.

Table 19 decocts orthogonal test factor level table

(1) index is selected: this product is drawn up into soft capsule, and the cream amount that gets of water extraction is bigger to the moulding process influence of finished product, so the water extraction process of this product is an index to receive the cream rate, carries out preferred; At the character of this product medical material, the yield that other measures 60% ethanol soluble extraction in the water extract guarantees the quality of this product.

(2) sample preparation: get 100g Fructus cinnamomi camphorae medical material, carry out water by each orthogonal test condition of table 19 and carry, medicinal liquid concentrates and is settled to 500ml after filtering with 300 order filter clothes.Standby.

(3) dried cream yield is measured: precision is got the medicinal liquid 25ml after each orthogonal test concentrates, put respectively in the evaporating dish that has been dried to constant weight, and water bath method, residue takes out in 105 ℃ of dryings 3 hours, puts in the exsiccator and places 30 minutes, weighs, and calculates dried cream yield.

(4) 60% ethanol soluble extractions are measured: precision is got the medicinal liquid 50ml after each orthogonal test concentrates, adding ethanol respectively makes and contains alcohol amount and reach 60%, left standstill cold preservation 24 hours, filter, the filtrate water bath method, residue was in 105 ℃ of dryings 3 hours, take out, place exsiccator to place 30 minutes, weigh, calculate the extractum yield.

Table 20 decocts the orthogonal experiments table

Annotate: dried cream yield scoring=(dried cream yield/maximum dry cream yield) * 40

60% ethanol soluble extraction scoring=(extractum yield/maximum extractum yield) * 60

Comprehensive grading=dried cream yield scoring+60% ethanol soluble extraction scoring

Table 21 decocts analysis of variance table

Annotate: F _0.05(2,2)=19.00; F _0.01(2,2)=99.00

From table 20,21 analysis results as can be known, each factor effect primary and secondary is A＞B＞C; Because of all having significant difference C, A, B factor do not have significant difference, A in the A factor among A, B, the C ₃＞A ₂＞A ₁So, select A ₃B in the B factor ₃＞B ₂＞B ₁So, select B ₃C in the C factor ₂＞C ₃＞C ₁So, select C ₂Therefore optimised process is A ₃B ₃C ₂, promptly add 8 times of water gagings, decocted 1.5 hours at every turn, decoct 1 time.

2.5.2 best decocting process checking is not included in 9 tests of orthogonal array, so it is verified owing to preferred optimised process. get orthogonal test with a collection of medical material, press A ₃B ₃C ₁Experimentize, verify 3 batches altogether, checking the results are shown in Table 22.

Table 22 decocts optimised process checking result

Checking is the result show, this technology extractum yield, 60% ethanol soluble extraction extracted amount are all more stable, can be used as the optimised process of extraction.

2.5.3 investigating workshop method for concentration commonly used, concentration technology have normal pressure to concentrate and concentrating under reduced pressure.Concentrating under reduced pressure have consuming time less, characteristics that thickening temperature is low, therefore heat-sensitive ingredients is destroyed lessly, along with improving constantly of pharmaceutical equipment manufacturing technology, present Chinese medicine workshop has been more, and to adopt concentrating under reduced pressure be main.For with produce actual combining closely, the concentrated mode of this product adopts the concentrating under reduced pressure method.

Get 1 times of recipe quantity medical material, extract by best decocting process, the decoction liquor concentrating under reduced pressure (0.06～-0.08Mpa, 80 ℃) to thick extractum, record this moment extractum relative density and be about 1.25 (60 ℃), it is an amount of to get extractum, the same method is measured wherein 60% ethanol soluble extraction, and result of the test sees Table 23.

Measurement result in table 23 concentrated extract

Result of the test shows: adopt pressure reducing mode that this product extracting solution is concentrated, 60% ethanol soluble extraction is stable in the prescription, and illustration method is feasible.

2.5.4 drying process we adopt normal pressure and drying under reduced pressure dual mode that drying process is investigated respectively: with the thick extractum mixing in the concentration technology investigation, be divided into 3 parts, carry out drying by condition in the table 9 respectively, 60% ethanol soluble extraction, color and luster, drying time in the gained extract powder to serve as the investigation object, with this drying mode is carried out preferably the results are shown in Table 24.

The different drying mode investigation tables of table 24

Last watch test result shows that drying mode and drying condition do not have obvious influence to 60% ethanol soluble extraction, but constant pressure and dry extractum color and luster is dark, required time is long, and by contrast, adopting decompression is that the drying process parameter is more suitable for 70 ℃.

2.5.5 it is bigger to the loading amount and the pressing process influence of soft capsule that disintegrating process is investigated the granularity of extract powder.Granule is more little, and soft capsule content is difficult for layering more, the spray orifice of also difficult more obstruction soft capsule press in the production process, and loading amount is stable more.Experience shows that crossing 120 purpose extract powders is ideal granularities.So it is grinding particle size that 120 orders are selected in this test for use, and dry extract is pulverized examination, the results are shown in Table 25.

Table 25 is pulverized yield and is investigated table as a result

This disintegrating process yield reaches more than 95%, and therefore ideal yield coefficient can be decided to be the dry extract grinding particle size 120 orders.

2.6 preparation process research

2.6.1 preparation prescription research

(1) disperse medium is selected with Study on Preparation 1

(2) the preferred research data of Cera Flava consumption shows in the disperse medium, in the disperse medium that is prepared into soybean oil and Cera Flava, mellisic consumption is generally 2%～5%, and in conjunction with this product extract powder character, we have done following investigation to mellisic concrete usage ratio in this product disperse medium: the according to the form below ratio is got Cera Flava and soybean oil, behind 80 ℃ of heating and meltings, be chilled to room temperature, add extract powder, grind evenly with colloid mill, observe its state, under room temperature, place and observed again in 2 weeks.The results are shown in Table 26.

Table 26

Result of the test explanation, it is slightly poor to add the content flowability that 4% Cera Flava is prepared in the soybean oil, is uniformly dispersed but lamination slightly, but under the equal conditions, to make the content flowability slightly poor though add 5% Cera Flava, do not have lamination, is Cera Flava consumption parameter in the disperse medium so select it.

(3) consumption of the preferred disperse medium of disperse medium consumption directly has influence on the dose and the content uniformity of soft capsule: ratio is low excessively, and then mobile bad, content uniformity is big; Ratio is excessive, and then consumption increases, the inconvenience of taking medicine.Therefore need the consumption of disperse medium is investigated, thus the optimum amount of definite disperse medium.By " the Cera Flava consumption is preferred in the disperse medium " test as can be known, when the usage ratio of extract powder and disperse medium (promptly containing 3% mellisic Semen sojae atricolor hot-melt object) is 1: 1, though it is good to be prepared into the stability of content, but flowability is slightly poor, therefore, we suitably increase the disperse medium consumption on this basis, and have carried out the investigation of 3 levels: the ratio of extract powder and disperse medium was respectively 1: 2,1: 2.5 and 1: 3.The results are shown in Table 27.

Table 27 disperse medium consumption is investigated

Result of the test shows, when adding 2 parts of disperse medium in 1 part of extract powder, it is less than normal to make the content flowability, when adding 4 parts of disperse medium, it is bigger than normal to make the content flowability, by contrast, the content flowability was moderate when extract powder and disperse medium were pressed 1: 3 mixed, and can determine to select this ratio is disperse medium consumption in this product.

The every prescription Blumeae preparatum Tabellae of this product 50g, Fructus cinnamomi camphorae medical material 300g, by preceding test as can be known, Fructus cinnamomi camphorae volatile oil extraction ratio is 6.0%, medicinal residues are about 10.0% through the rate of extract after extracting purification again, be that every prescription is prepared into volatile oil 18g, the about 30g of dry extract, adding 3 times of amount disperse medium (promptly adding disperse medium 294g) back total amount is 392g.Consider and add to help batching and the calculating of finished product loading amount into the dispensed in small quantity medium, and the stability of content is not had influence, therefore, we are adjusted into 302g with every prescription disperse medium consumption, and promptly adding disperse medium adjustment total amount is 400g.

(4) the rubber prescription is preferably with Study on Preparation 1

2.6.2 the preparations shaping technical study is with Study on Preparation 1

3, soft capsule loading amount and dose are determined

According to recipe quantity and Study on Preparation data computation this product loading amount and dose.

(1) loading amount is determined Fructus cinnamomi camphorae 300g in this product prescription, and the volatile oil extraction ratio is 6%, extracts back the rate of extract and is about 10.0%, be that every prescription is prepared into volatile oil 18g, the about 30g of dry extract, Blumeae preparatum Tabellae 50g, adding disperse medium (containing 3% mellisic Semen sojae atricolor hot-melt object) to total amount is 400g.Full side is made 1000, and then every loading amount is 0.4g.

(2) dose is determined the full side of former XINWEI ZHITONG JIAONANG 175g altogether, makes 1000, and every contains crude drug 0.175g, takes 2 at every turn, is equivalent to take crude drug 0.35g.After dosage form changed, every of heart stomach and alleviating pain soft capsule was equivalent to take crude drug 0.35g, therefore, promptly each 1, every day 3 times.

Three, soft capsule pharmacodynamic study

(1) soft capsule is used for the main pharmacodynamics research of gastric abscess

1, soft capsule is used for the animal experiment of chronic gastritis

1.1 animal model is prepared: the immunization of imitative document duplicates the tentative chronic gastritis model of rabbit, and with homozoic gastric mucosa homogenate and complete Freund adjuvant, immune animal is strengthened once behind the 10d again, begins medication after continuing to observe 10d.

1.2 observation index after the medication: pathological changes area (product of the millimeter of pathological changes transverse diameter), ulcer number.

1.3 result of the test: behind the animal immune 10-15d, the part animal food-intake occurs and descends, do not take food, symptoms such as movable difference are behind the booster immunization 10d, above-mentioned performance is more obvious, the weight of animals obviously alleviates, and postmortem finds that gastric mucosa is the dispersivity inflammation, soaks into based on neutrophilic granulocyte and mononuclear phagocyte, and visible eosinophilic granulocyte, each layer of coat of the stomach all has in various degree congested and hemorrhage.Pathological changes area (table 28) behind the medication 10d, the high, medium and low dosage of soft capsule, XINWEI ZHITONG JIAONANG and model group relatively have marked difference (P＜0.05), soft capsule height, middle dosage obviously are better than XINWEI ZHITONG JIAONANG, microscopy shows, the experimental group stomach lining inflammation disappears substantially, connective tissue proliferation in the serous coat, and the matched group gastric mucosa is the dispersivity inflammation, based on neutrophilic granulocyte and monocyte infiltration, with hyperemia in various degree, hemorrhage, edema

Table 28 soft capsule is to the influence of chronic gastritis

Group	Dose g/kg/d	Pathological changes area (mm 2)	Ulcer number (individual)	Suppression ratio (%)
					Model group	??0	??80.16±33.6	??0.5±0.55
The soft capsule low dose group	??0.2	??19.34±9.0	??0.26±0.3	??71.2
					Dosage group in the soft capsule	??0.4	??14.56±7.2	??0.24±0.3	??82.9
The soft capsule high dose group	??0.8	??12.22±8.4	??0.18±0.3	??88.1
					XINWEI ZHITONG JIAONANG	??1.0	??18.35±8.2	??0.20±0.3	??73.1

2, to the influence of pylorus ligation gastric ulcer: get 50 of rats, male and female half and half, body weight 190～240g divides 5 groups: blank group (N.S), positive controls (XINWEI ZHITONG JIAONANG) and the high, medium and low dosage group of soft capsule at random.After gastric infusion or N.S2 days, fasting 24 hours places rat in the bell jar, behind etherization, be fixed on the Mus plate, cut off belly wool, sterilization, from ensiform process of sternum lower edge ventrimeson open abdomen, find out stomach, behind the ligation stomach pylorus, every Mus is by duodenal administration or N.S1 time, sew up flesh layer and skin, fasting and water were put to death animal after 18 hours, opened the abdominal cavity, the ligation cardia, full stomach is taken out, cut coat of the stomach along greater gastric curvature, clean gastric content, coat of the stomach is launched, write down every group and produce ulcer Mus and ulcer index, experimental result sees Table 29.Experimental result shows: the ulcer index of each group of administration is starkly lower than the blank group.Show that this medicine can suppress the formation of rat pylorus ligation gastric ulcer, wherein soft capsule height, middle dosage group are better than the XINWEI ZHITONG JIAONANG group.

Table 29 soft capsule is to the influence of pylorus ligation gastric ulcer (n=10, X ± S)

Group	Number of animals	Dosage (g/kg)	Ulcer index	The P value
					Blank group	??10	??---	??23.65±6.34
The soft capsule low dose group	??10	??0.4	??15.68±5.56	??＜0.05
					The soft capsule low dose group	??10	??0.8	??12.23±4.04	??＜0.05
The soft capsule low dose group	??10	??1.2	??10.46±5.25	??＜0.05
					XINWEI ZHITONG JIAONANG	??10	??2.0	??13.46±6.25	??＜0.05

3, influence to chronic gastric ulcer due to the glacial acetic acid: rat number, body weight and sex are with test 2, test 2 method open abdomen are pressed in the animal fasting after 8 hours, finding out stomach gently moves to outside the abdomen, facies ventralis at stomach, body of stomach and pyloric antrum are assigned place's serous coat and are injected 20% ice vinegar 0.05ml down, to send stomach back to abdominal cavity gently and sew up flesh layer and skin then. operation divides 5 groups next day at random, grouping, dosage, route of administration is with experiment 2, every day, gastric infusion was 1 time, successive administration 12 days, the 13rd day execution rat, open abdomen, ligation pylorus and cardia, and inject 1% formaldehyde 8ml in gastric, the tailing edge greater gastric curvature was cut off in 30 minutes, stomach is turned up, outwell gastric content, measure the gastric ulcer area, and calculate the ulcer healing percentage rate, experimental result sees Table 30. experimental results and shows: each group of administration all can be dwindled the ulcer area and be improved ulcer healing rate, and has compared significant difference. the soft capsule height, middle dosage is better than the XINWEI ZHITONG JIAONANG group.

Table 30 soft capsule is to the influence of chronic gastric ulcer due to the glacial acetic acid (n=10, X ± S)

Group	Number of animals	Dosage (g/kg)	Ulcer index	The P value	Healing rate
						Blank group	??10	??---	??21.46±3.28
The soft capsule low dose group	??10	??0.4	??13.52±4.16	??＜0.01	??46.78
						The soft capsule low dose group	??10	??0.8	??10.46±5.24	??＜0.01	??58.42
The soft capsule low dose group	??10	??1.2	??7.86±3.64	??＜0.01	??64.86
						XINWEI ZHITONG JIAONANG	??10	??2.0	??12.24±4.18	??＜0.01	??52.45

4, to the excretory influence of ligation pylorus rat gastric juice: rat number, body weight, sex, grouping, dosage and route of administration are with test 2, and water is can't help in administration fasting 24 hours two days later.Behind etherization, cut flatly along abdomen is just online, find out stomach, the ligation pylorus.By duodenal administration or N.S1 time, sew up incision of abdominal wall, open the abdominal cavity after 4 hours, collect gastric juice, record gastric juice amount, centrifugal 10 minutes again with 3000rpm, to get supernatant and measure free acid, total acidity and pepsin activity the results are shown in Table 31.Experimental result shows: each group of administration obviously suppresses gastric secretion, reduces gastric acid and pepsic output, and wherein soft capsule height, middle dosage are better than the XINWEI ZHITONG JIAONANG group.

Table 31 soft capsule is to the excretory influence of ligation pylorus rat stomach (n=10, X ± S)

Group	Gastric juice amount (ml)	Free acid (mol/L)	Total acidity (mol/L)	Total acid output (mol/L)	Pepsin activity (u/ml)	Pepsin output (u/ hour)
							Blank group	??9.26±??2.37	??86.48±??6.46	??88.56±??6.68	??152.64±??7.16	??212.44±??28.47	??289.45±??21.34
Low dose group	??6.82±??2.74*	??68.83±??8.13**	??116.17±??16.11**	??176.00±??14.66**	??164.46±??18.65**	??212.24±??16.86**
							Middle dosage group	??5.92±??2.63*	??60.42±??2.16**	??98.83±??15.91**	??154.44±??34.23**	??154.65±??38.28**	??186.54±??28.78**
High dose group	??5.04±??2.56**	??51.64±??5.46**	??60.32±??12.92**	??112.37±??15.42**	??108.26±??14.39**	??132.67±??17.65**
							The hard capsule group	??6.36±??2.46*	??64.83±??8.54**	??112.24±??18.32**	??160.68±??18.12**	??160.78±??15.56**	??202.46±??16.86**

Annotate:, * P＜0.05 * * P＜0.01

(2) soft capsule is to angina pectoris animal influence experiment

1, isoproterenol is caused the hypoxia endurance test of mice: with the grouping of mice according to the form below, successive administration 7 days.1h after the last administration, lumbar injection isoprenaline (15mg/kg) is put in the wide mouthed bottle that the people fills the 10g sodica calx record death time respectively behind the 15min.Carry out 3 experiments altogether, the results are shown in Table 32.Experimental result shows: each group of administration obviously prolongs the death time that isoproterenol causes the mice anoxia enduring, and wherein the middle and high dosage of soft capsule is better than XINWEI ZHITONG JIAONANG.

Table 32 soft capsule causes the influence of mice anoxia enduring to isoproterenol

Group	Number of animals	Dosage (g/kg)	Death time (branch)
				Blank group	??10	??-	??21.22±3.65
The soft capsule low dose group	??10	??0.4	??26.78±1.86
				Dosage group in the soft capsule	??10	??0.8	??30.46±2.43
The soft capsule high dose group	??10	??1.6	??38.82±3.16
				XINWEI ZHITONG JIAONANG	??10	??2.0	??29.18±2.43

2, to the experiment of myocardial ischemia hemorheology drug action: dog is through the eleventh of the twelve Earthly Branches barbital sodium (30mg.kg ^-1) iv anesthesia, tracheal intubation connects SC-3 type electric pulmotor; Left side the 4th intercostal is opened breast, separates M-LAD, and threading causes acute experiment myocardial ischemia " syndrome of blood stasis " model in order to ligation; The suffered reagent thing of equal-volume that gives to have prepared through duodenum; Through the external jugular vein intubate to coronary sinus vein, behind coronary ligation 15min (before the medicine) and medicine 30,60,120,180min blood drawing, 10g.L ^-1EDTAK ₂Anticoagulant is adopted NXE-1 type cone-plate viscosity apparatus to carry out the whole blood height and is cut (η _Bh), the low (η that cuts _B1) viscosimetric analysis; Anticoagulation 3000r.min ^-1, centrifugal 10min takes out blood plasma XN ₃Capillary viscosimeter is measured blood plasma (η _p) ratio of viscosity and normal saline viscosity; Use XN ₃Cell electrophoresis self-clocking instrument detects the electrophoresis time (EET) of erythrocyte in self blood plasma.Reference literature detects the whole blood height and cuts viscosity (η _Bh), the low viscosity (η that cuts _B1), plasma viscosity (η _p), Fibrinogen (Fib) and hematocrit hemorheology indexs such as (Hct).Data are judged its significance with the t check.

2.1 influence: compare the η of two dosage groups each time point after administration with matched group to the dog blood viscosity _Bh, η _B1, all on a declining curve, crude drug 2g.kg ^-1Group is better than crude drug 1g.kg ^-1Group; 180min to the coronary ligation, η _p, EPT and matched group more all have remarkable decline (P＜0.05, P＜0.01 Tab1), see Table 33.

Table 33 soft capsule is to influence (n=5, xq ± s, the 3mL.kg of dog hemorheology index ^-1)

aP＜0.05，bP＜0.01vscontrol；cP＜0.05，dP＜0.01vspre2treatment。

2.2 influence: compare 1 week of administration back whole blood η before and after the treatment to the coronary heart disease hemorheology _Bh, η _B1, all there were significant differences for Hct and Fib (P＜0.05), sees Table 34.

Table 34 soft capsule is to the hemorheological influence of coronary heart disease blood high viscosity syndrome

^aP＜0.05vs?pre-treatment.

(3) 50 of mices are got in the influence that causes mice ear of soft capsule xylol, 20 ± 1g, and male and female half and half are divided into blank group (NS), the high, medium and low dosage group of soft capsule and XINWEI ZHITONG JIAONANG group at random.Each organizes gastric infusion, every day 1 time, and continuous 4 days, after the last administration 1 hour, be coated with each Mus auris dextra with dimethylbenzene 0.03ml and cause inflammation, cut ears after 2 hours, to get auricle with the 9mm card punch and weigh respectively, left and right sides auricle weight difference is the swelling degree, calculates inhibitory rate of intumesce.See Table 35.

Table 35 soft capsule to the bullate influence of mice dimethylbenzene ear (X ± S, n=10)

Group	Number of animals	Dosage (g/kg)	Swelling degree (mg)	Suppression ratio (%)
					Blank group (NS)	??10	??--	??18.8±4.2	??--
The soft capsule low dosage	??10	??0.4	??7.6±2.2**	??59.58
					Dosage in the soft capsule	??10	??0.8	??5.9±2.3**	??68.62
The soft capsule high dose	??10	??1.6	??3.8±2.6**	??79.79
					XINWEI ZHITONG JIAONANG	??10	??2.0	??6.6±2.0**	??64.89

With NS group ratio, * * P＜0.01

The result shows that the high, medium and low dosage group of soft capsule all can obviously suppress the mice caused by dimethylbenzene xylene auricle edema, with NS group ratio, with t check, difference highly significant (P＜0.01).Soft capsule height, middle dosage are better than XINWEI ZHITONG JIAONANG.

(4) analgesic activity (mouse writhing method) is got 50 of mices, 20 ± 1g male and female half and half, grouping and the same preceding paragraph of administration, after the last administration 1 hour, every Mus lumbar injection 0.6% acetic acid 0.1ml/10g caused pain, and each Mus is turned round the body number of times in the immediate record 15min, calculate suppression ratio, see Table 36.

Table 36

Group	Number of animals	Dosage (g/kg)	Turn round body number of times (15min)	Suppression ratio (%)
					Blank group (NS)	??10	??--	??32.4±6.8	??--
The soft capsule low dosage	??10	??0.4	??18.2±5.8**	??43.83
					Dosage in the soft capsule	??10	??0.8	??14.1±4.6**	??56.48
The soft capsule high dose	??10	??1.6	??12.6±6.4**	??61.11
					XINWEI ZHITONG JIAONANG	??10	??2.0	??16.5±2.7**	??49.07

With NS group ratio, * P＜0.05

The result shows that the high, medium and low dosage group of soft capsule all can suppress the writhing response that acetic acid causes mice, with NS group ratio, significant difference (P＜0.05).Soft capsule height, middle dosage all are better than XINWEI ZHITONG JIAONANG.

(5) conclusion: this soft capsule can obviously suppress chronic gastric ulcer due to rat pylorus ligation gastric ulcer and the glacial acetic acid; Can suppress the rat gastric secretion; Reduce gastric acid and pepsin output; Can significantly improve hemorheology, can resist the contraction of intestinal smooth muscle due to the Ach. in addition, can also obviously suppress the swollen acetic acid that reaches of mice caused by dimethylbenzene xylene ear and cause the mouse writhing reaction, having antiinflammatory and analgesic activity. this soft capsule compares with positive control drug (XINWEI ZHITONG JIAONANG), and wherein soft capsule height, middle dosage all are better than XINWEI ZHITONG JIAONANG in every index.

Four, soft capsule acute toxicity testing

Summary is observed the acute toxicity of medicine of the present invention to mice.Mice single gastric infusion does not have death, can't obtain median lethal dose(LD 50), adopts maximum dosage-feeding 100g/kg.d (three times on the 1st filling stomaches) to observe continuously 14 days, do not see dead mouse, generally in order, no abnormal discovery shows that medicine of the present invention is very low to chmice acute toxicity.See Table 37.

1. experiment material

1.1 the animal Kunming mouse, body weight 18～22g.Provide the quality certification number by Animal Experimental Study chamber, Chongqing Institute of Chinese Medicine: SCXK (Chongqing) 20060004.

1.2 medicine medicated powder of the present invention.Wear into fine powder with mortar before the experiment, it is standby to be mixed with suspension with distilled water.

2, method

2.1 measure median lethal dose(LD 50) (LD ₅₀): 40 of female mices, body weight 18～22g is divided into 4 groups (10/group): be respectively medicine 18g/kg.d of the present invention at random ^-1, 20g/kg.d ^-1, 22g/kg.d ^-1, 24g/kg.d ^-1(maximum suspendible concentration), fasting (can't help water) single gastric infusion after 12 hours, each 0.4ml/10g, ordinary circumstance (body weight change, diet, fur, behavior, secretions, Excreta etc.) of observation mice and poisoning, death condition were observed 14 days continuously.

2.2 maximum dosage-feeding experiment: 20 of female mices, body weight 18～22g, administration volume 0.4ml/10g, 100g/kg.d divide gastric infusion three times, observe general activity situation and the death toll of mice, observe continuously 14 days.

3, result

3.1 medicine of the present invention is not seen death during respectively organizing mouse test, (body weight, diet, fur, behavior, secretions, Excreta etc.) can't obtain LD generally in order ₅₀

3.2 adopt maximum dosage-feeding 100g/kg.d (be equivalent to approximately clinical every day of dosage 250 times) to irritate stomach, duration of test mice body weight all increases, diet and movable normal, fur is smooth, no abnormality seen secretions such as mouth, nose, eye only were the brown soft stool on the 1st day after the administration, the urine no abnormality seen.

4. the experiment of conclusion maximum dosage-feeding shows that medicine of the present invention is very low to chmice acute toxicity.

The comparison of table 37 soft capsule maximum dosage-feeding experiment mice body weight

Grouping	Number of animals (only)	Before the administration (g)	1 week (g) after the administration	2 weeks (g) after the administration
					Preparation of the present invention (100g/kg.d)	??20	??20.4±1.6	??22.6±1.3	??24.2±1.2

Five, clinical research

(1) clinical report of heart stomach and alleviating pain soft capsule treatment stomach institute pain

This product heart stomach and alleviating pain soft capsule is according to utilizing natural drug Fructus cinnamomi camphorae, Herba Blumeae Balsamiferae extract to make with extra care and form on the Guizhou minority nationality proved recipe basis.Be used for the treatment of acute or chronic gastritis, stomach takes off diseases such as pain, abdominal part distension, pantothenic acid vomiting and nausea, dyspepsia, with this medicine treatment stomach institute pain 90 examples, compares treatment 60 examples with XINWEI ZHITONG JIAONANG simultaneously, now reports as follows.

1, clinical data

1.1 physical data: the administration group is totally 90 examples, male's 48 examples wherein, women's 42 examples.Minimum 12 years old of age, maximum 65 years old, the course of disease the shortest half a year, elder 24 years.Matched group 60 examples, male's 32 examples wherein, women's 28 examples.Minimum 14 years old of age, maximum 65 years old, the course of disease the shortest half a year, elder 26 years.

1.2 Chinese medical discrimination typing: (1) treatment group: syndrome of stagnation of QI 36 examples, coagulated cold syndrome 28 examples, deficiency-cold syndrome 26 examples. (2) matched group: syndrome of stagnation of QI 22 examples, coagulated cold syndrome 20 examples, deficiency-cold syndrome 18 examples.

1.3 Western medicine diagnose: (1) treatment group: make a definite diagnosis 90 examples through fibergastroscopy, chronic superficial gastritis 18 examples wherein, atrophic gastritis 22 examples, gastric ulcer 20 examples, duodenal ulcer 30 examples.(2) matched group: make a definite diagnosis 60 examples through fibergastroscopy, chronic superficial gastritis 12 examples wherein, atrophic gastritis 18 examples, gastric ulcer 13 examples, duodenal ulcer 17 examples.

2, diagnostic criteria

2.1 epigastric pain diagnostic criteria: 1. stomach institute pain pain and gastrointestinal disease symptom; 2. history of repeated attack is arranged; 3. premorbid has obvious inducement.More than 1. possess in three, 2., 3. item has one concurrently and diagnosablely is stomach institute pain.

2.2 pattern of syndrome diagnostic criteria

1. coagulated cold syndrome: primary symptom: stomachache is done cruelly, based on angor, meets and coldly promptly sends out or increase the weight of, and pain alleviated while getting warmth is brought out by exogenous cold or eating cold and uncooked food excessively more than the morbidity; Tongue is white, tense pulse or string.Inferior disease: loss of appetite, then happiness heat of food; Tastelessness, general vomiting watery fluid; The stool pool is thin, clear urine in large amounts.Primary symptom possesses, and it is promptly diagnosable to have time disease binomial concurrently.

2. syndrome of stagnation of QI: primary symptom: stomach institute distending pain, attack and scurry both sides of the chest, heating installation or flatus then relax, tongue fur is white, stringy pulse.Inferior disease: meet angry recurrence or increase the weight of; Lack of appetite uncomfortable in chest, warm rotten acid regurgitation; The stool molding, defecation is not smooth.Primary symptom possesses, and it is promptly diagnosable to have time disease binomial concurrently.

3. deficiency-cold syndrome: primary symptom: stomachache is indistinct, desire for warm and being pressed; Pain must be eaten alleviation of pain, abdominal distention after meal on an empty stomach; Pale and tender tongue, there is indentation on the limit, white and thin fur, deep-thready pulse or slow.Inferior disease: lassitude, spiritlessness and sparing of words, aversion to cold and cold limbs; It is quiet thin to defecate, or the pool, just hard back; Inappetence, the food posterior umbilicus is vexed.Have three of primary symptoms or primary symptom front and back binomial and have time disease binomial concurrently promptly diagnosable.

3, observation and Therapeutic Method

3.1 Therapeutic Method: (1) treatment group: oral heart stomach and alleviating pain soft capsule, each 1, every day 3 times, 7 days is a course of treatment.(2) matched group: oral XINWEI ZHITONG JIAONANG, each 2, every day 3 times, 7 days is a course of treatment.

Other medicines (medicine that comprises other treatment gastropathy) that affect the treatment and observe of stopping using during the previous day and the treatment of taking medicine, period in a medicine is avoided cold and uncooked food and excitant food.

3.2 observation item and method: case before treatment, in the treatment, treatment finishes, the project of observing table according to the clinical verification of formulating respectively the observed and recorded patient symptom, sign, picture of the tongue, pulse condition once, before routine blood test, routine urinalysis, the stool routine examination treatment, treatment finishes each observed and recorded once.

4, curative effect is judged and therapeutic outcome

4.1 curative effect is judged: clinical cure: primary symptom and disease all disappear, part sign such as picture of the tongue, and the commentaries on classics though pulse condition is not got better does not also increase the weight of, and celebrates mutually with physico-chemical examination and recovers substantially normally or be clearly better; Produce effects: primary symptom all has clear improvement with time disease, or indivedual primary symptom slightly improves, but other primary symptom, inferior disease all disappear; Take a turn for the better: primary symptom, inferior disease all have improvement or primary symptom that improvement is not arranged, but inferior disease all disappears; Invalid: primary symptom, inferior disease all do not have change or do not reach above-mentioned standard person.

4.2 therapeutic effect

4.2.1 total effects: organize in 90 examples in treatment, clinical cure 22 examples account for 24.44%; Produce effects 35 examples account for 38.89%; Cure-remarkable-effectiveness rate reaches 63.33%, and 29 examples that take a turn for the better account for 32.22%; Invalid 4 examples account for 4.44%.Total effective rate 95.56%.In contrast 60 examples, clinical cure 13 examples account for 21.67%; Produce effects 22 examples account for 36.67%; Cure-remarkable-effectiveness rate reaches 58.34%, and 18 examples that take a turn for the better account for 30.0%; Invalid 7 examples account for 11.67%.Total effective rate 88.33%.Two groups relatively, and soft capsule treatment group clinical efficacy is better than contrasting heart stomach and alleviating pain hard capsule group.Two groups relatively as table 38.

The clinical total effects comparing result of table 38 treatment group and matched group

Group	Case load (example)	Cure example (%)	Produce effects example (%)	Cure-remarkable-effectiveness rate (%)	Effectively routine (%)	Invalid example (%)	Total effective rate (%)
								The treatment group	??90	??22??24.44	??35??38.89	??63.33	??29??32.22	??4??4.44	??95.56
Matched group	??60	??13??21.67	??22??36.67	??58.34	??18??30.0	??7??11.67	??88.33

4.2.2 different pattern of syndrome efficacy analysis: through the Chinese medical discrimination typing, (1) treatment group: syndrome of stagnation of QI 36 examples, coagulated cold syndrome 28 examples, deficiency-cold syndrome 26 examples.(2) matched group: syndrome of stagnation of QI 22 examples, coagulated cold syndrome 20 examples, deficiency-cold syndrome 18 examples.Two groups to different pattern of syndrome curative effects comparisons as table 39-41.

Table 39 liang group is at the gastric abscess efficacy result of stagnation of QI disease

Table 40 liang group is at the gastric abscess efficacy result of coagulated cold syndrome

Table 41 liang group is at the gastric abscess efficacy result of deficiency-cold syndrome

4.2.3 doctor trained in Western medicine efficacy analysis: press Western medicine diagnose, chronic superficial gastritis 18 examples in (1) treatment group, atrophic gastritis 22 examples, gastric ulcer 20 examples, duodenal ulcer 30 examples.(2) chronic superficial gastritis 12 examples in the matched group, atrophic gastritis 18 examples, gastric ulcer 13 examples, duodenal ulcer 17 examples.Two groups of doctor trained in Western medicine curative effects are relatively as table 4244.

Table 42 liang group is at treatment chronic superficial gastritis efficacy result

Table 42 liang group is at treatment chronic superficial gastritis efficacy result

Table 43 liang group is at treatment atrophic gastritis efficacy result

Table 44 liang group is at the routed smelt efficacy result of treatment stomach

Two groups at treatment duodenal ulcer efficacy result

5, brief summary: the average total effective rate of heart stomach and alleviating pain soft capsule treatment stomach institute pain is 95.56%; Heart stomach and alleviating pain soft capsule treatment stomach institute's pain (being divided into cold coagulation disease, stagnation of QI disease, deficiency-cold symptoms) all has obvious curative effects, the treatment total effective rate there was no significant difference of three disease types; The average total effective rate of matched group (XINWEI ZHITONG JIAONANG) treatment stomach institute pain is 88.33%, two group and compares the treatment group matched group that is better than evident in efficacy.Heart stomach and alleviating pain soft capsule analgesic effect is fast, shows the superiority of this product; Heart stomach and alleviating pain soft capsule treatment gastric abscess, particularly remarkable to the improvement of symptoms such as sudden pain, angor, cold type of pain, distending pain; Two groups there is no untoward reaction in the clinical trial process, show that this product safety is good, are a kind of safe and effective medicine, are worth clinical expansion to use.

The specific embodiment

Embodiment 1: weighting raw materials material Fructus cinnamomi camphorae 300g, Blumeae preparatum Tabellae 50g.Get Blumeae preparatum Tabellae, pulverize, cross 120 mesh sieves, standby; Get Fructus cinnamomi camphorae and add 3 times of water gagings, soak 3h, distillation extraction 8 hours; Get volatile oil, standby; Get soybean oil 316g, Cera Flava 16g, heating and melting, be chilled to room temperature after, add volatile oil and Blumeae preparatum Tabellae 50g mix homogeneously, colloid mill ground 15 minutes, was pressed into 1000, promptly got soft capsule of the present invention.Every of this product dress 0.4g, oral, one time 1,3 times on the one, 7 days is a course of treatment; Take in ante cibum or the meal.

Embodiment 2: weighting raw materials material Fructus cinnamomi camphorae 300g, Blumeae preparatum Tabellae 50g.Get Blumeae preparatum Tabellae, pulverize, cross 120 mesh sieves, standby; Get the Fructus cinnamomi camphorae supercritical CO ₂Extraction volatile oil, standby; Get soybean oil 320g, Cera Flava 20g, heating and melting, be chilled to room temperature after, add volatile oil and Blumeae preparatum Tabellae 50g mix homogeneously, colloid mill ground 15 minutes, was pressed into 1000, promptly got soft capsule of the present invention.Every of this product dress 0.4g, oral, one time 1,3 times on the one, 7 days is a course of treatment; Take in ante cibum or the meal.

Embodiment 3: weighting raw materials material Fructus cinnamomi camphorae 150g, Blumeae preparatum Tabellae 25g.Get Blumeae preparatum Tabellae, pulverize, cross 120 mesh sieves, standby; Get Fructus cinnamomi camphorae and add 3 times of water gagings, soak 3h, distillation extraction 8 hours; Get volatile oil, standby; Get soybean oil 158g, Cera Flava 8g, heating and melting, be chilled to room temperature after, add volatile oil and Blumeae preparatum Tabellae 25g mix homogeneously, colloid mill ground 15 minutes, was pressed into 500, promptly got soft capsule of the present invention.Every of this product dress 0.4g, oral, one time 1,3 times on the one, 7 days is a course of treatment; Take in ante cibum or the meal.

Embodiment 4: weighting raw materials material Fructus cinnamomi camphorae 150g, Blumeae preparatum Tabellae 25g.Get Blumeae preparatum Tabellae, pulverize, cross 120 mesh sieves, standby; Get the Fructus cinnamomi camphorae supercritical CO ₂Extraction volatile oil, standby; Get soybean oil 150g, Cera Flava 10g, heating and melting, be chilled to room temperature after, add volatile oil and Blumeae preparatum Tabellae 25g mix homogeneously, colloid mill ground 15 minutes, was pressed into 500, promptly got soft capsule of the present invention. every dress of this product 0.54g, oral, one time 1,3 times on the one, 7 days is a course of treatment; Take in ante cibum or the meal.

Embodiment 5: weighting raw materials material Fructus cinnamomi camphorae 15000g, Blumeae preparatum Tabellae 2500g.Get Blumeae preparatum Tabellae, pulverize, cross 120 mesh sieves, standby; Get the Fructus cinnamomi camphorae supercritical CO ₂Extraction volatile oil, standby; Get soybean oil 15800g, Cera Flava 800g, heating and melting, be chilled to room temperature after, add volatile oil and Blumeae preparatum Tabellae 2500g mix homogeneously, colloid mill ground 15 minutes, was pressed into 50000, promptly got soft capsule of the present invention.Every of this product dress 0.4g, oral, one time 1,3 times on the one, 7 days is a course of treatment; Take in ante cibum or the meal.

Embodiment 6: weighting raw materials material Fructus cinnamomi camphorae 30kg, Blumeae preparatum Tabellae 5kg.Get Blumeae preparatum Tabellae, pulverize, cross 120 mesh sieves, standby; Get Fructus cinnamomi camphorae and add 3 times of water gagings, soak 3h, distillation extraction 8 hours; Get volatile oil, standby; Get soybean oil 31.6kg, Cera Flava 1.6kg, heating and melting, be chilled to room temperature after, add volatile oil and Blumeae preparatum Tabellae 5kg mix homogeneously, colloid mill ground 15 minutes, was pressed into 100000, promptly got soft capsule of the present invention.Every of this product dress 0.4g, oral, one time 1,3 times on the one, 7 days is a course of treatment; Take in ante cibum or the meal.

Embodiment 7: weighting raw materials material Fructus cinnamomi camphorae 300g, Blumeae preparatum Tabellae 50g.Get Blumeae preparatum Tabellae, pulverize, cross 120 mesh sieves, standby; Get Fructus cinnamomi camphorae and add 3 times of water gagings, soak 3h, distillation extraction 8 hours is got volatile oil, and is standby; Water liquid after the distillation filters, and device is collected in addition, and is standby; Medicinal residues behind the extraction volatile oil add 8 times of water gagings and decoct 1 time, and each 1.5 hours, collecting decoction, filter, merge with above-mentioned water liquid, concentrating under reduced pressure (65～75 ℃) is to the thick paste of relative density 1.30～1.35 (60 ℃), drying under reduced pressure (60～70 ℃) is pulverized, and crosses 120 mesh sieves.Get soybean oil 280g, Cera Flava 20g, heating and melting, be chilled to room temperature after, add volatile oil, Blumeae preparatum Tabellae mix homogeneously, admix extract powder, mix homogeneously, colloid mill ground 15 minutes, was pressed into 1000, promptly got soft capsule of the present invention.Every of this product dress 0.4g, oral, one time 1,3 times on the one, 7 days is a course of treatment; Take in ante cibum or the meal.

Embodiment 8: weighting raw materials material Fructus cinnamomi camphorae 150g, Blumeae preparatum Tabellae 25g.Get Blumeae preparatum Tabellae, pulverize, cross 120 mesh sieves, standby; Get the Fructus cinnamomi camphorae supercritical CO ₂Extraction volatile oil, standby; Medicinal residues behind the extraction volatile oil add 8 times of water gagings and decoct 2 times, and each 1.5 hours, collecting decoction filtered, and concentrating under reduced pressure (65～75 ℃) is to the thick paste of relative density 1.30～1.35 (60 ℃), and drying under reduced pressure (60～70 ℃) is pulverized, and crosses 120 mesh sieves.Get soybean oil 140g, Cera Flava 10g, heating and melting, be chilled to room temperature after, add volatile oil, Blumeae preparatum Tabellae mix homogeneously, admix extract powder, mix homogeneously, colloid mill ground 15 minutes, was pressed into 500, promptly got soft capsule of the present invention.Every of this product dress 0.4g, oral, one time 1,3 times on the one, 7 days is a course of treatment; Take in ante cibum or the meal.

Embodiment 9: weighting raw materials material Fructus cinnamomi camphorae 600g, Blumeae preparatum Tabellae 100g.Get Blumeae preparatum Tabellae, pulverize, cross 120 mesh sieves, standby; Get Fructus cinnamomi camphorae and add 2 times of water gagings, soak 1h, distillation extraction 5 hours; Get volatile oil, standby; Get soybean oil 630g, Cera Flava 30g, heating and melting, be chilled to room temperature after, add volatile oil and Blumeae preparatum Tabellae 100g mix homogeneously, colloid mill ground 15 minutes, was pressed into 2000, promptly got soft capsule of the present invention.Every of this product dress 0.4g, oral, one time 1,3 times on the one, 7 days is a course of treatment; Take in ante cibum or the meal.

Embodiment 10: weighting raw materials material Fructus cinnamomi camphorae 3000g, Blumeae preparatum Tabellae 500g.Get Blumeae preparatum Tabellae, pulverize, cross 160 mesh sieves, standby; Get Fructus cinnamomi camphorae and add 4 times of water gagings, soak 5h, distillation extraction 12 hours; Get volatile oil, standby; Get soybean oil 3200g, Cera Flava 150g, heating and melting, be chilled to room temperature after, add volatile oil and Blumeae preparatum Tabellae 500g mix homogeneously, colloid mill ground 15 minutes, was pressed into 10000, promptly got soft capsule of the present invention.Every of this product dress 0.4g, oral, one time 1,3 times on the one, 7 days is a course of treatment; Take in ante cibum or the meal.

Embodiment 11: weighting raw materials material Fructus cinnamomi camphorae 30kg, Blumeae preparatum Tabellae 5kg. get Blumeae preparatum Tabellae, pulverize, and cross 140 mesh sieves, and be standby; Get Fructus cinnamomi camphorae and add 2 times of water gagings, soak 2h, distillation extraction 10 hours is got volatile oil, and is standby; Water liquid after the distillation filters, and device is collected in addition, and is standby; Medicinal residues behind the extraction volatile oil add 6 times of water gagings and decoct 2 times, and each 1 hour, collecting decoction, filter, merge with above-mentioned water liquid, concentrating under reduced pressure (65～75 ℃) is to the thick paste of relative density 1.30～1.35 (60 ℃), drying under reduced pressure (60～70 ℃), pulverize, cross 140 mesh sieves. get soybean oil 28kg, Cera Flava 2kg, heating and melting, after being chilled to room temperature, add volatile oil, the Blumeae preparatum Tabellae mix homogeneously is admixed extract powder, mix homogeneously, colloid mill ground 15 minutes, was pressed into 100000, promptly got soft capsule of the present invention. every dress of this product 0.4g, oral, one time 1,3 times on the one, 7 days is a course of treatment; Take in ante cibum or the meal.

Embodiment 12: weighting raw materials material Fructus cinnamomi camphorae 665g, Blumeae preparatum Tabellae 35g.Get Blumeae preparatum Tabellae, pulverize, cross 160 mesh sieves, standby; Get Fructus cinnamomi camphorae and add 4 times of water gagings, soak 2h, distillation extraction 6 hours; Get volatile oil, standby; Get soybean oil 620g, Cera Flava 30g, heating and melting, be chilled to room temperature after, add volatile oil and Blumeae preparatum Tabellae 35g mix homogeneously, colloid mill ground 15 minutes, was pressed into 2000, promptly got soft capsule of the present invention.Every of this product dress 0.4g, oral, one time 1,3 times on the one, 7 days is a course of treatment; Take in ante cibum or the meal.

Embodiment 13: weighting raw materials material Fructus cinnamomi camphorae 1050g, Blumeae preparatum Tabellae 350g.Get Blumeae preparatum Tabellae, pulverize, cross 120 mesh sieves, standby; Get Fructus cinnamomi camphorae and add 2 times of water gagings, soak 4h, distillation extraction 10 hours; Get volatile oil, standby; Get soybean oil 1100g, Cera Flava 80g, heating and melting, be chilled to room temperature after, add volatile oil and Blumeae preparatum Tabellae 350g mix homogeneously, colloid mill ground 15 minutes, was pressed into 4000, promptly got soft capsule of the present invention.Every of this product dress 0.4g, oral, one time 1,3 times on the one, 7 days is a course of treatment; Take in ante cibum or the meal.

Embodiment 14: weighting raw materials material Fructus cinnamomi camphorae 2800g, Blumeae preparatum Tabellae 700g.Get Blumeae preparatum Tabellae, pulverize, cross 140 mesh sieves, standby; Get the Fructus cinnamomi camphorae supercritical CO ₂Extraction volatile oil, standby; Medicinal residues behind the extraction volatile oil add 10 times of water gagings and decoct 2 times, and each 2 hours, collecting decoction filtered, and concentrating under reduced pressure (65～75 ℃) is to the thick paste of relative density 1.30～1.35 (60 ℃), and drying under reduced pressure (60～70 ℃) is pulverized, and crosses 140 mesh sieves.Get soybean oil 2950g, Cera Flava 200g, heating and melting, be chilled to room temperature after, add volatile oil, Blumeae preparatum Tabellae mix homogeneously, admix extract powder, mix homogeneously, colloid mill ground 15 minutes, was pressed into 10000, promptly got soft capsule of the present invention.Every of this product dress 0.4g, oral, one time 1,3 times on the one, 7 days is a course of treatment; Take in ante cibum or the meal.

Embodiment 13: weighting raw materials material Fructus cinnamomi camphorae 630g, Blumeae preparatum Tabellae 70g.Get Blumeae preparatum Tabellae, pulverize, cross 160 mesh sieves, standby; Get the Fructus cinnamomi camphorae supercritical CO ₂Extraction volatile oil, standby; Get soybean oil 270g, Cera Flava 20g, heating and melting, be chilled to room temperature after, add volatile oil and Blumeae preparatum Tabellae 70g mix homogeneously, colloid mill ground 15 minutes, was pressed into 2000, promptly got soft capsule of the present invention.Every of this product dress 0.2g, oral, one time 1,3 times on the one, 7 days is a course of treatment; Take in ante cibum or the meal.

Embodiments of the present invention are not limited to the foregoing description, and the various variations of making under the prerequisite that does not break away from aim of the present invention all belong within protection scope of the present invention.

Claims (8)

1. Chinese medicinal soft capsule for the treatment of gastralgia is characterized in that: calculate according to percentage by weight, it adds appropriate amount of auxiliary materials by Fructus cinnamomi camphorae 75～95% and Blumeae preparatum Tabellae 5～25% and is prepared into soft capsule.

2. according to the Chinese medicinal soft capsule of the described treatment gastralgia of claim 1, it is characterized in that: calculate according to percentage by weight, it adds appropriate amount of auxiliary materials by Fructus cinnamomi camphorae 85.7% and Blumeae preparatum Tabellae 14.3% and is prepared into soft capsule.

3. as the preparation method of the Chinese medicinal soft capsule of treatment gastralgia as described in claim 1 and 2, it is characterized in that: take by weighing Fructus cinnamomi camphorae and Blumeae preparatum Tabellae; Get Fructus cinnamomi camphorae with steam distillation or supercritical carbon dioxide extraction volatile oil, standby; Get oleaginous base and suspending agent, heating and melting, be chilled to room temperature after, add said extracted volatile oil and Blumeae preparatum Tabellae mix homogeneously, make soft capsule.

4. according to the preparation method of the Chinese medicinal soft capsule of the described treatment gastralgia of claim 3, it is characterized in that: take by weighing Fructus cinnamomi camphorae and Blumeae preparatum Tabellae; Get Fructus cinnamomi camphorae, add 3 times of water gagings, soak 3h, distillation extraction 8h; Get volatile oil, standby; Get soybean oil and Cera Flava is an amount of, heating and melting, be chilled to room temperature after, add above-mentioned volatile oil and Blumeae preparatum Tabellae mix homogeneously, colloid mill ground 15 minutes, was pressed into soft capsule.

5. according to the preparation method of the Chinese medicinal soft capsule of the described treatment gastralgia of claim 3, it is characterized in that: take by weighing Fructus cinnamomi camphorae and Blumeae preparatum Tabellae; Get Blumeae preparatum Tabellae, pulverize, cross 120 mesh sieves, standby; Get Fructus cinnamomi camphorae, supercritical CO 2 extraction volatile oil, standby; Get soybean oil and Cera Flava is an amount of, heating and melting, be chilled to room temperature after, add above-mentioned volatile oil and Blumeae preparatum Tabellae mix homogeneously, colloid mill ground 15 minutes, was pressed into soft capsule.

6. treat the preparation method of the Chinese medicinal soft capsule of gastralgia as claimed in claim 1 or 2, it is characterized in that: take by weighing Fructus cinnamomi camphorae and Blumeae preparatum Tabellae; Get Fructus cinnamomi camphorae, with steam distillation or supercritical carbon dioxide extraction volatile oil, standby; Water liquid after the distillation filters, and device is collected in addition, and is standby; The medicinal residues that extract behind the volatile oil decoct with water 1～3 time, and each 0.5～2 hour, collecting decoction filtered, and merge with water liquid after the distillation, are evaporated to the thick paste of 60 ℃ of relative densities 1.30～1.35, and drying is pulverized, and crosses 100 orders with top sieve, extract powder, standby; Get oleaginous base and suspending agent, heating and melting, be chilled to room temperature after, add said extracted volatile oil and Blumeae preparatum Tabellae mix homogeneously, add above-mentioned extract powder, mix homogeneously is made soft capsule.

7. according to the preparation method of the Chinese medicinal soft capsule of the described treatment gastralgia of claim 6, it is characterized in that: take by weighing Fructus cinnamomi camphorae and Blumeae preparatum Tabellae; Get Blumeae preparatum Tabellae, pulverize, cross 120 mesh sieves, standby; Get Fructus cinnamomi camphorae, add 3 times of water gagings, soak 3h, distillation extraction 8 hours is got volatile oil, and is standby; Water liquid after the distillation filters, and device is collected in addition, and is standby; Medicinal residues behind the extraction volatile oil add 8 times of water gagings and decoct 1 time, each 1.5 hours, collecting decoction filters, with the water liquid merging after the distillation, under 65～75 ℃, be evaporated to the thick paste of 60 ℃ of relative densities 1.30～1.35, at 60～70 ℃ of following drying under reduced pressure, pulverize, cross 120 mesh sieves, get extract powder, standby; Get soybean oil and Cera Flava is an amount of, heating and melting, be chilled to room temperature after, add said extracted volatile oil and Blumeae preparatum Tabellae mix homogeneously, add above-mentioned extract powder, mix homogeneously, colloid mill ground 15 minutes, was pressed into soft capsule.

8. according to the preparation method of the Chinese medicinal soft capsule of the described treatment gastralgia of claim 6, it is characterized in that: take by weighing Fructus cinnamomi camphorae and Blumeae preparatum Tabellae; Get Blumeae preparatum Tabellae, pulverize, cross 120 mesh sieves, standby; Get Fructus cinnamomi camphorae supercritical CO 2 extraction volatile oil, standby; Medicinal residues behind the extraction volatile oil add 8 times of water gagings and decoct 2 times, and each 1.5 hours, collecting decoction filtered, under 65～75 ℃, be evaporated to the thick paste of 60 ℃ of relative densities 1.30～1.35,, pulverize at 60～70 ℃ of following drying under reduced pressure, cross 120 mesh sieves, get extract powder, standby; Get soybean oil and Cera Flava is an amount of, heating and melting, be chilled to room temperature after, add above-mentioned volatile oil and Blumeae preparatum Tabellae mix homogeneously, add above-mentioned extract powder, mix homogeneously, colloid mill ground 15 minutes, was pressed into soft capsule.