TWI571257B - Capsule preparation - Google Patents

Description

Capsule preparation

The invention relates to the technical field of medical preparations, in particular to a pharmaceutical capsule preparation prepared by processing a capsule shell of different colors and materials.

Compound Danshen Dripping Pill is a new generation of medicine for treating cardiovascular diseases, which is exclusively produced by Tianjin Tianshili Pharmaceutical Co., Ltd. Compound Danshen Dripping Pills are made of Danshen as a drug, Sanqi as a drug, and borneol as an adjuvant. They are used to treat blood circulation, relieve phlegm, relieve pain and aroma. They are mainly used for the treatment of cardiovascular diseases. At present, the compound Danshen Dripping Pills in the domestic market are packaged in high-density polyethylene bottles in the specifications of 180 pills/bottle, 150 pills/bottle, 100 pills/bottle, and 60 pills/bottle. Take 10 pills each time you take it. However, this type of administration is less accepted abroad. In order to enter the international market, the applicant plans to further make the compound Danshen Dripping Pill into a capsule preparation.

As edible packaging materials for medicines and foods, capsule shells of different nature may have certain effects on the stability of medicines and foods. Currently, hard capsule shells sold on the market are generally divided into gelatin capsule shells and plant capsule shells. .

The gelatin capsule shell is made of a protein product obtained by partially hydrolyzing and purifying collagen from the skin, bone and tendons of an animal, and the capsule shell contains a large amount of strontium. Fish gelatin capsule shell is a new type of gelatin capsule shell developed in recent years.

The plant capsule shell is a capsule shell made of a plant-derived raw material (the raw material contains a polysaccharide and a basic component of a plant cell wall), for example, hydroxypropylmethylcellulose (HPMC). At present, the common plant capsule shells are a plant capsule shell made of pullulan, a plant capsule shell made of seaweed polysaccharide, and a plant capsule shell made of hydroxypropylmethylcellulose.

The transparent capsule shell is more likely to enhance the affinity of Chinese medicine to customers and enhance sensory awareness, which is widely welcomed by the international market. However, the transparent capsule shells of different colors reflect the light of different wavelength bands, which causes the medicine to receive light of different wavelengths. Therefore, the transparent capsule shells of different colors have certain influence on the stability of the drug itself. In addition, capsule shells of different materials have different effects on the stability of the drug due to differences in hygroscopicity, stability, and physicochemical properties of the material itself.

In order to obtain the best protective effect of the drug, the applicant has studied the effect of capsule shells of different materials and colors on the stability of the drug after a long period of research, and the capsule shell which is beneficial to the stability of the drug is selected through screening.

The object of the present invention is to provide a compound Danshen dripping pill capsule with good stability.

The capsule preparation of the present invention is prepared from a drug and a capsule shell, and the medicine is filled in a capsule shell, wherein the capsule shell is a colored capsule shell, and the medicine is a compound Danshen dripping pill.

The color of the capsule shell is preferably an orange-yellow-green-blue capsule shell, and the corresponding wavelength range is 446 nm to 620 nm.

The preferred color of the capsule shell is: orange, corresponding wavelength range is 592nm-620nm; blue, corresponding wavelength range is 446nm-500nm; yellow, corresponding wavelength range is 577nm-592nm; and green, corresponding wavelength range It is 500nm-577nm.

The color of the optimal capsule shell is yellow, the corresponding wavelength range is 577nm-592nm; and the green color, the corresponding wavelength range is 500nm-577nm.

The capsule shell is selected from the group consisting of a gelatin capsule shell and a plant capsule shell.

From the material point of view, the capsule shell is preferably a plant capsule shell.

The compound Danshen dripping pill of the invention is prepared from Danshen, Sanqi and borneol.

Preferably, the compound Danshen dropping pills of the present invention are made of the following weight percentages of the drug substance relative to the total weight of the three Chinese herbal medicines: salvia miltiorrhiza, notoginseng and borneol:

Salvia miltiorrhiza 48.0%-97.0%

Sanqi 1.0%-50.0%

Borneol 0.1%-3.0%.

More preferably, the compound Danshen dropping pills of the present invention are made of the following weight percentages of the drug substance relative to the total weight of the three Chinese herbal medicines: salvia miltiorrhiza, notoginseng and borneol:

Salvia 63.0%-94.0%

Sanqi 4.0%-35.0%

Borneol 0.5%-2.0%.

Most preferably, the compound Danshen dropping pills of the present invention are made of the following weight percentages of the drug substance relative to the total weight of the three Chinese herbal medicines: salvia miltiorrhiza, notoginseng and borneol:

Salvia 82.87%

Sanqi 16.21%

Borneol 0.92%.

Herein, the drug substance is relative to the excipient, and the drug substance is an active ingredient in the preparation. In the present text, the raw material medicine refers to a raw medicine or a Chinese medicine decoction piece which has not been further purified. The auxiliary material refers to a general term for all the medicinal materials except for the raw material medicine, which are added to the prescription in order to solve the moldability, effectiveness, stability and safety of the preparation at the time of prescription design of the preparation.

The drug substance is processed as follows before the formulation is carried out:

The Salvia miltiorrhiza is the dried root and rhizome of the dicotyledonous Labiatae salvia miltiorrhiza Bge. Salvia miltiorrhiza can be sliced or crushed for use.

The five feed means thirty-seven thirty-seven plant Panax notoginseng (Bμrk.) FH Chen dried roots and rhizomes.

The borneol is a crystal obtained by extracting the resin of the dipterocarp plant Dipterocarp and the volatile oil processed product, and can also be obtained by chemical synthesis, and can be finely sieved for use before use.

The preparation of the traditional Chinese medicine composition of the present invention can be carried out by a method of the prior art, for example, Chinese Patent Application No. 01136155.7, 01820875.4, 03144300.1, 200310107279.5, 200410018758.4, 200410019827.3 and 02100884.1, the disclosure of which is hereby incorporated by reference.

For example, Danshen, Sanqi medicinal materials, boiling water or alkaline water can be taken, filtered, and the filtrate is combined, and the filtrate is appropriately concentrated; ethanol is added to the concentrated solution for alcohol deposition, and the ethanol is recovered in the supernatant. Concentrated into Danshen Sanqi extract; the obtained extract is mixed with borneol and auxiliary materials to form a dropping pill.

Specifically, the compound Danshen dropping pills can be prepared according to the following steps: the Danshen and the Panax notoginseng are weighed according to the above ratio, and extracted by heating and refluxing in water or an aqueous solution of pH 7-9 for 2-4 times, each time extracting 0.5-3 hours. The reflux extraction temperature is 60-100 ° C, the weight of each added water is 2-12 times the weight of the medicinal material, the obtained extract is filtered, the filtrate is concentrated to a relative density of 1.05-1.25, and the alcohol is added to the liquid solution to have an alcohol content of 50. %-85%(v/v), standing for 4 to 36 hours, filtering the supernatant, recovering the ethanol, and collecting the extract to an extract having a sugar content of 50-90 brix (ie, Danshen Sanqi extract); the present invention The matrix adjuvant used in the compound Danshen dropping pills may be polyethylene glycol-6000, the freezing point of which is 53-58 ° C, and the weight ratio of the raw material drug to the auxiliary material is 1: (0.31 - 0.49); After the borneol and the auxiliary materials are uniformly mixed, the mixture (i.e., the chemical) is heated and melted, transferred to a drip tank of the dropping machine, and the molten medicine is dropped into a low-temperature cooling liquid (for example, liquid paraffin) to remove the cooling liquid, and the selected sample is can. The temperature of the chemical is 60-100 ° C; the temperature of the cooling liquid is 0-10 ° C, preferably 5-10 ° C.

Further, the compound Danshen dropping pill of the present invention contains an auxiliary material, which may be only a matrix auxiliary material, or a combination of a matrix auxiliary material and a plasticizing auxiliary material. Wherein, the matrix adjuvant used may also be a natural matrix adjuvant of plant origin, for example, may be selected from pharmaceutically acceptable D-ribose, fructose, xylose, trehalose, raffinose, maltose, agarose, sucrose ester, D - ribose-γ-lactone, erythritol, sorbitol, xylitol, arabinol, isomalt, lactitol, malic acid, glyceryl stearate, shellac, phenylethylene glycol, a polyoxyethylene alkyl ether, and the above compound containing crystal water; the auxiliary material may further comprise a plasticizing auxiliary material, which may be selected, for example, from pregelatinized starch, carboxymethyl starch, gum arabic, dextran, and phthalocyanine. Carrageenan (carrageenan), Indian gum, red algae gum, scutellaria gum, tamarind gum, pectin, xanthan gum, alginic acid and its salts, agar, lactose, glyceryl monostearate, Polyoxyethylene monostearate, croscarmellose sodium, cerium oxide, and the like.

The compound Danshen dripping pill can be a vegetarian pill or a coated pill.

Wherein, the specific preparation method of the compound pellet of the compound Danshen dropping pill can be, for example:

<ingredients> Danshen, Sanqi, borneol

<Preparation method> Take Danshen Sanqi extract, add 2.5-3.5 times of the weight of the extract of polyethylene glycol-6000, and make the material at 85-90 °C. After the chemical is even, add the finely sieved according to the prescription amount. The borneol is stirred and mixed, and transferred to a dropping machine at 80-85 ° C to obtain a drop.

The specific preparation method of the coated pellet of the compound Danshen dripping pill can be, for example:

<ingredients> Danshen, Sanqi, borneol

<Preparation method> Take Danshen Sanqi extract, add 2.5-3.5 times of the weight of the extract of polyethylene glycol-6000, and make the material at 85-90 °C. After the chemical is even, add the finely sieved according to the prescription amount. The borneol was stirred and mixed, and transferred to a dropping machine at 80-85 ° C to obtain a pellet of the pellet. According to the proportion of coating weight gain of 6wt%, dissolve the stomach-soluble coating material with water, stir well, transfer the pellets to the coating equipment, and the average inlet air temperature is 85 °C, the average bed temperature is 35-38 °C. The coating is obtained under the conditions of an atomization pressure of 2 bar, an average rotation speed of 15-23 rpm, and an average material flow rate of 3-4 g/min.

The compound Danshen dripping pill capsule of the present invention produced an unexpected effect and was further confirmed by the following experiment.

The experimental capsule shell was purchased from Sino-US joint venture Suzhou Capsule Co., Ltd. and is one of the production bases of Pfizer Capsule (CAPSMGEL).

Test method

The capsules of different colors and materials were selected to be filled with compound Danshen dropping pills as test samples. The contents of various components of Danshen, Sanqi and Borneol were detected by HPLC, MV and GC in the environment of intense light irradiation and accelerated test. .

2. Instruments and samples 2.1 Instrumentation

Stability Test Case (MMM) CLIMACELL 404 with lighting function.

High Performance Liquid Chromatograph Agilent 1100

UV-visible spectrometer Hitachi M3010

Gas chromatograph Agilent 8890

2.2 sample 2.2.1 Compound Danshen Dripping Pills (taken from the production department of Tianjin Tianshili Pharmaceutical Co., Ltd.)

According to the purpose of the test and the technical feasibility, the compound Danshen Xiao Drop Pills was selected as the test sample, and the production line of Tianjin Tianshili Pharmaceutical Co., Ltd. was used for dripping. The test samples were divided into two types: coated pill and vegetarian pill. The average pill weight of the small drop pill is 10 mg, and the ordinary No. 1 capsule can be filled with 30-35 tablets.

The dropping process of compound Danshen dripping pills:

(1) Droplet Pills

Salvia 41.06g Sanqi 8.03g borneol 0.46g

Excipients Polyethylene Glycol-6000 18g

Made of 1000 pills

Extraction of Salvia miltiorrhiza and Sanqi

Take the coarsely pulverized Salvia miltiorrhiza Bge. and Radix Notoginseng herbs into the extraction tank, add 5 times the amount of water of the Salvia miltiorrhiza and Radix Notoginseng, boil for 2 hours, filter, filter the residue for the second extraction, add the Danshen and Sanqi herbs. 4 times the amount of water, decocted for 1 hour, filtered, the filter residue was discarded, and the filtrate was combined. The filtrate was concentrated under reduced pressure to a relative density of 1.05, and 95% (v/v) of ethanol was slowly added thereto to make the drug solution having an alcohol concentration of 69-71% (v/v) and allowed to stand for 12 hours. The supernatant of the drug solution after alcohol deposition was filtered, and the filtrate was recovered to ethanol, and the extract was collected to an extract having a sugar content of 50 brix (ie, Salvia miltiorrhiza extract).

Product preparation

Take Danshen Sanqi extract, add 2.5-3.5 times of the weight of the extract of polyethylene glycol-6000, at 85-90 °C, after the chemical is even, add the finely sifted borneol according to the prescription, stir Mix and transfer to a dropping machine at 80-85 ° C to obtain.

<Specification> The average pill weight is 10 mg/pill.

(2) Small drop pill coated pills

Salvia 41.06g Sanqi 8.03g borneol 0.46g

Excipients Polyethylene Glycol-6000 18g

Made of 1000 pills

Extraction of Salvia miltiorrhiza and Sanqi

The crude smashed Danshen and Sanqi medicinal materials were taken into the extraction tank, and 5 times of the NaOH aqueous solution of the Salvia miltiorrhiza and the Panax notoginseng was added, and the NaOH solution was decocted for 2 hours, filtered, and the filter residue was extracted for the second time. Four times the amount of the above alkaline solution of the medicinal material of Panax notoginseng, decocted for 1 hour, filtered, and the filter residue was discarded, and the filtrate was combined. The filtrate was concentrated under reduced pressure to a relative density of 1.25, and 95% (v/v) of ethanol was slowly added to make the drug solution having an alcohol concentration of 69-71% (v/v) and allowed to stand for 12 hours. The supernatant of the drug solution after alcohol deposition was filtered, and the filtrate was recovered to ethanol, and the extract was collected to an extract having a sugar content of 90 brix (ie, Salvia miltiorrhiza extract).

Product preparation

Take Danshen Sanqi extract, add 2.5-3.5 times of the weight of the extract of polyethylene glycol-6000, at 85-90 °C, after the chemical is even, add the finely sifted borneol according to the prescription, stir Mix and transfer to a dropping machine at 80-85 ° C to obtain a small drop pill.

Dissolving the stomach-soluble coating material in water at a ratio of 6 wt% of the weight gain of the coating, fully stirring, and transferring the pill into the coating device at an average inlet air temperature of 85 ° C, an average bed temperature of 35-38 ° C, The coating was carried out under the conditions of an atomization pressure of 2 bar, an average rotation speed of 15-23 rpm, and an average material flow rate of 3-4 g/min, that is, a small drop pill coated pellet.

<Specification> The average pill weight is 11 mg/pill.

2.2.2 Capsule shell (from Sino-US joint venture Suzhou Capsule Co., Ltd.)

Capsule shells of gelatin and plant are used to cover 16 kinds of capsule shells of red, orange, yellow, green, cyan, blue and purple in the visible light range (Table 1).

2.2.3 Test sample

Different combinations of 17 kinds of drop pills and capsule shells were selected for testing, and capsules or coated pellets were filled in capsule shells of different materials and colors (Table 2).

3. Test process 3.1 Test content

The test is divided into two parts, the strong light irradiation test and the accelerated stability test.

3.1.1 glare test

Strong light irradiation conditions: temperature is 25 ° C, relative humidity is 60%, and wind speed is 100%. Set 40% light, 10 cm distance. The irradiation intensity reached 4500 Lμx. Samples were taken on days 0, 5, and 10.

First select two samples of MWB and MWS to investigate whether the light will affect the compound Danshen dropping pills; then select the gelatin capsule shells of different colors and the same material of MBBB, MBZBB, MCB, MZB, MHB, MHMB, MLB, MGB, MBHB. Nine samples of coated pellets were taken to investigate the protective effects of capsule shells of different colors under the irradiation of strong light on compound Danshen dropping pills.

3.1.2 Accelerated stability test

Accelerated test conditions: temperature 40 ° C, relative humidity 75%. Samples were taken in the months of January, January, February, March, April, and June.

The capsules and coated pellets of the compound Danshen dripping pills were prepared in the capsule shells of the above 17 different colors and materials, and the degree of change of the compound Danshen dripping pills in the whole process of the accelerated test was investigated.

3.2 test indicators

Determination of the content of the following components: Danshen in the indicator components: Danshensu, protocatechuic aldehyde, salvianolic acid L, salvianolic acid M, salvianolic acid D, rosmarinic acid, salvianolic acid B and salvianolic acid A; Indicator components in Panax notoginseng: R1, Rg1+Re, Rb1, Rc, Rb2, Rb3 and Rd; total phenolic acid, total saponin and total sugar; and borneol.

The appearance changes, and the appearance changes of the dropping pills under the limit conditions are examined. Whether it is dry or wet, whether it is agglomerated, whether white precipitates appear on the surface, whether the color and the weight of the pellet change.

3.3 Test methods 3.3.1 Fingerprint spectrum and content determination method of Danshen index components

3.3.1.1 Preparation of test materials

Take 10 samples of compound Danshen dropping pills in each sample in a 10 ml volumetric flask, add appropriate amount of distilled water, supersonic for 15 min, dilute to volume, and centrifuge. The above samples were prepared in two portions at the same time. The injection volume of each sample was 10 μl.

Take Danshensu, protocatechuic aldehyde, rosmarinic acid, salvianolic acid B, salvianolic acid A, salvianolic acid L, salvianolic acid M, salvianolic acid D standard preparation standard solution, injection of each sample The amount is 10 μl.

3.3.1.2 HPLC method

Agilent SB-C18 analytical column (4.6mm × 250mm)

Mobile phase: Phase A: 0.02% (v/v) aqueous phosphoric acid; Phase B: 80% acetonitrile in water containing 0.02% (v/v) phosphoric acid

Linear gradient elution program: 0min (90:10), 8min (78:22), 15min (74:26), 35min (61:39)

The flow rate was 1 ml/min, the detection wavelength was 280 nm, and the column temperature was 30 °C.

The retention time of each indicator component in Salvia miltiorrhiza Bunge was: 5.842min of Danshensu, 9.750min of protocatechuic aldehyde, 17.106min of salvianolic acid L, 18.041min of salvianolic acid M, 20.588min of salvianolic acid D, rosmarinic acid 24.005 min, salvianolic acid B was 27.908 min, and salvianolic acid A was 31.085 min.

3.3.2 Fingerprint spectrum and content determination method of indicator components of Sanqi

3.3.2.1 Preparation of test materials

Take 1g of each sample, dissolve it in 10ml of 4% (v/v) ammonia water, dissolve all the ultrasonic waves, pass 0.45μm filter, take 5ml filtrate through C18 column, wash with 10ml water, elute with methanol, make up to 10ml capacity In the bottle. The above samples were prepared in two portions at the same time. The injection volume of each sample was 20 μl.

A standard solution was prepared from the standards of R1, Rg1+Re, Rb1, Rc, Rb2, Rb3, and Rd, and the injection amount of each sample was 20 μl.

3.3.2.2 HPLC method

Agilent SB-C18 analytical column (4.6mm × 250mm)

Mobile phase: Phase A: 0.01% (v/v) aqueous acetic acid; Phase B: aqueous acetonitrile solution containing 0.01% (v/v) acetic acid.

The linear gradient elution program is shown in the following table:

The flow rate was 0.8 ml/min, the detection wavelength was 203 nm, and the column temperature was 30 °C.

The retention time of each indicator component in Panax notoginseng was: R1 was 11.001min, Rg1+Re was 12.252min, Rb1 was 20.142min, Rc was 20.877min, Rb2 was 22.418min, Rb3 was 23.422min, and Rd was 25.151min.

3.3.3 Determination method of content of various major components

3.3.3.1 Total phenolic acid content

The protocatechuic aldehyde solution is a reference solution, and 0.3 wt% sodium dodecyl sulfate and 0.6 wt% potassium ferricyanide solution and 0.9 wt% ferric chloride solution are added to the reference solution, the sample solution and the blank control solution. Using the color reaction, the total phenolic acid content in the sample was calculated according to the comparison method of the reference substance.

3.3.3.2 Total saponin content

The ginsenoside Rg1 solution was used as a reference solution, and a coloring reaction was carried out by adding 5 wt% vanillin-glacial acetic acid solution and perchloric acid, and a standard curve was prepared by taking the absorbance of the standard solution of different concentrations to calculate the total saponin content in the sample.

3.3.3.3 Total sugar content

Glucose was used as the reference solution, and the fluorenone reagent was added to develop a color reaction. The standard curve was prepared by the absorbance of the standard solution of different concentrations, and the total sugar content in the sample was calculated.

3.3.4 Determination of borneol content

3.3.4.1 Preparation of test articles

The naphthalene standard was used as the internal standard solution, and the standard solution was prepared from the borneol and isobornyl standards, and the injection amount was 1 μl.

Weigh 0.5 g of the crushed coated pellets, add 10 ml of water in a 50 ml plastic centrifuge tube, add 25 ml of ethyl acetate to shake vigorously, and extract the extract with a pipette into a 50 ml volumetric flask. In this way, it was extracted twice with ethyl acetate, and the amount of ethyl acetate used in each extraction was 10 ml. The extracts were combined, 4 ml of internal standard solution was added, and finally, the volume was adjusted to the mark with ethyl acetate, and shaken to serve as a test. Product solution. The injection volume was 1 μl.

3.3.4.2 Chromatographic conditions

HP5% PHME siloxana 30m (column length) × 0.25mm (film thickness) quartz capillary column; column temperature: from 60 ° C, the temperature is raised to 135 (150) ° C at 15 ° C / min, maintained for 2 min, the total process 8 min; FID (hydrogen flame ionization detector); 240 ° C; carrier gas: nitrogen; flow rate: 2.6 ml / min; gasification chamber temperature 200 ° C; theoretical plate number according to naphthalene should not be less than 10,000, the degree of separation is greater than 2.

3.3.5 Data Statistics Method

Two-tailed paired t-test (software: SPSS 13.0) was subjected to t-test to determine whether the indicators had significant changes under the experimental conditions.

The efficiency evaluation model is used to evaluate the advantages and disadvantages of the packaging. The method used in the process is Data Envelopment Analysis (DEA). The specific model is a super-efficiency model. The different packages are used to examine the objects. The initial indicators of different packages are input objects, and the measured values of different indicators are output. The object is calculated by the MYDEA software to obtain the component retention efficiency of each package in different months. The less the component loss, the higher the efficiency value and vice versa.

4. Experimental results 4.1 Strong light irradiation experimental data

Samples of the capsules of 9 colors were sampled at 0, 5, and 10 days for inspection of 19 indicator components (see Table 3-6). The 19 indicator components are the eight indicator components of the Salvia miltiorrhiza (Table 3), the seven indicator components of the Panax notoginseng (Table 4), and the three major components (total phenolic acid, total saponin, and total sugar). Table 5); and borneol (Table 6).

4.2 Accelerated stability experimental data

Samples of capsule shells of 17 different materials and colors were sampled at 0, 1, 2, 3, 4.5, and 6 months, and the above 19 indicators were tested (see Table 7-10) and the judgment of appearance changes (see table). 11).

4.3 Data Analysis Results

4.3.1 Statistical analysis results of experimental data of strong light irradiation (see Table 12)

4.3.2 Statistical analysis results of accelerated stability test data (see Table 13)

4.3.3 Accelerated stability test The t-test results of the evaluation results after the significant change index and the evaluation results of all the indicators (see Table 14)

4.3.4 Final evaluation results of 17 capsule shells (see Table 15)

5 .in conclusion 5.1 better material for capsule shell

As a result of the accelerated test, it is seen that the protective effect on the contents of the capsule shell, whether from the appearance of the dropping pills and the content of the components, is more preferably the capsule shell of the capsule than the shell of the gelatin capsule.

5.2 The preferred color of the capsule shell

According to the statistical results of the strong light irradiation test data (Table 12), the glare has an effect on the components of the compound Danshen dropping pills, and the protective ability of the capsule shells of different colors is different, but as long as it is a colored capsule shell The content will be protected, and the opaque white will be ranked last in both the significant indicator and the score of all indicators. The experimental data can also sort the capsule shells of different colors. In general, the preferred color is an orange-yellow-green-blue capsule shell having a corresponding wavelength range of 446 nm to 620 nm. Specifically, the orange system has a corresponding wavelength range of (592 nm to 620 nm); the blue system has a corresponding wavelength range of (446 nm to 500 nm); the yellow system has a corresponding wavelength range of 577 nm to 592 nm and a green color, and the corresponding wavelength range is 500 nm. -577nm. Among them, it can scatter the medium-wavelength visible light (500-592nm), that is, the yellow (corresponding wavelength range is 577nm-592nm) and the green (corresponding wavelength range is 500nm-577nm) capsule shell, which protects the compound Danshen dripping pills. The strongest.

5.3 Long-term stability test selection basis

Based on the final statistical results of the accelerated stability experiment (Table 15), the following conclusions can be drawn:

(1) For the material of the capsule, the plant capsule shell is superior to the gelatin capsule shell; (2) For the color of the capsule, an orange-yellow-green-blue capsule shell is preferred, and the corresponding wavelength range is 446 nm- 620 nm; more preferably a yellow shell (corresponding to a wavelength range of 577 nm to 592 nm) and a green shell (corresponding to a wavelength range of 500 nm to 577 nm); (3) combining the above two considerations, preferably for the compound Danshen dripping pill capsule The capsule shells are: plant yellow capsule shell, plant green capsule shell, gelatin yellow capsule shell and gelatin green capsule shell. In addition, for the color of the capsule shell, the wavelength range can be appropriately relaxed to orange and blue.

In summary, the compound Danshen dripping pill capsule of the present invention is beneficial for maintaining the physical and chemical properties of the compound Danshen dripping pills and the stability of the active ingredients.

The invention is further illustrated by the following detailed description.

Example 1 small drop pill Formulation dosage

Salvia 41.06g Sanqi 8.03g borneol 0.46g

Excipients Polyethylene Glycol-6000 18g

Made of 1000 pills

Extraction of Salvia miltiorrhiza and Sanqi

Take the coarsely pulverized Salvia miltiorrhiza and Radix Notoginseng herbs into the extraction tank, add 5 times the amount of water of the above-mentioned Danshen and Sanqi medicinal materials, decoct for 2 hours for filtration, filter residue for the second extraction, and add the Danshen and Sanqi medicinal materials. Double the amount of water, decoct for 1 hour, filter, discard the filter residue, and combine the filtrate. The filtrate was concentrated under reduced pressure to a relative density of 1.05, and 95% (v/v) of ethanol was slowly added to make the drug solution having an alcohol concentration of 69-71% (v/v) and allowed to stand for 12 hours. The supernatant of the alcohol solution was taken, filtered, and the filtrate was recovered to ethanol, and the extract was collected to an extract having a sugar content of 50 brix.

Take Danshen Sanqi extract, add 2.5-3.5 times of the weight of the extract of polyethylene glycol-6000, at 85-90 °C, after the chemical is even, add the finely sifted borneol according to the prescription, stir Mix and transfer to a dropping machine to obtain a pellet at 80-85 ° C. Finally, the obtained pellet is wrapped with a 586 nm yellow plant capsule shell.

Example 2 Small Drop Pills

The pharmaceutical composition was prepared in the same manner as in Example 1. After obtaining the pellet, the 572 nm green plant capsule shell was wrapped.

Example 3 Droplet Pills

The pharmaceutical composition was prepared in the same manner as in Example 1. After obtaining the pellet, the plant capsule shell having a wavelength of 500 nm was coated.

Example 4 Small Drop Pills

The pharmaceutical composition was prepared in the same manner as in Example 1. After obtaining the pellet, the 592 nm yellow plant capsule shell was wrapped.

Example 5 Droplet Pills

The pharmaceutical ingredient was prepared in the same manner as in Example 1. After obtaining the pill, the plant capsule shell having a corresponding wavelength of 577 nm was wrapped.

Example 6 Droplet Pills

The pharmaceutical composition was prepared in the same manner as in Example 1. After obtaining the pellet, the plant capsule shell having a corresponding wavelength of 592 nm was wrapped.

Example 7 Droplet Pills

The pharmaceutical composition was prepared in the same manner as in Example 1. After obtaining the pellet, the 620 nm orange plant capsule shell was wrapped.

Example 8 Droplet Pills

The pharmaceutical composition was prepared in the same manner as in Example 1. After obtaining the pellet, the 466 nm blue plant capsule shell was wrapped.

Example 9 Droplet Pills

The pharmaceutical composition was prepared in the same manner as in Example 1. After the pellet was obtained, a yellow plant capsule shell of 580 nm was coated.

Example 10 Droplet Pills

The pharmaceutical composition was prepared in the same manner as in Example 1. After obtaining the pellet, it was wrapped with a 460 nm blue plant capsule shell.

Example 11 Droplet Pills

The pharmaceutical composition was prepared in the same manner as in Example 1. After obtaining the pellet, the green plant capsule shell of 550 nm was wrapped.

Example 12 Small Drop Pill Coated Pills Formulation dosage

Salvia 41.06g Sanqi 8.03g borneol 0.46g

Excipients Polyethylene Glycol-6000 18g

Made of 1000 pills

Extraction of Salvia miltiorrhiza and Sanqi

The coarsely pulverized Danshen and Sanqi medicinal materials were taken into the extraction tank, and 5 times of the NaOH aqueous solution of the Salvia miltiorrhiza and the Panax notoginseng was added, and the mixture was decocted for 2 hours for filtration, and the filter residue was extracted for the second time, and the Salvia miltiorrhiza was added. Four times the amount of the above alkaline solution of the medicinal material of Panax notoginseng was boiled for 1 hour, filtered, and the filter residue was discarded, and the filtrate was combined. The filtrate was concentrated under reduced pressure to a relative density of 1.25, and 95% (v/v) of ethanol was slowly added to make the drug solution having an alcohol concentration of 69-71% (v/v) and allowed to stand for 12 hours. The supernatant of the drug solution after alcohol deposition was filtered, and the filtrate was recovered to ethanol, and the extract was collected to an extract having a sugar content of 90 brix.

Take Danshen Sanqi extract, add 2.5-3.5 times of the weight of the extract of polyethylene glycol-6000, at 85-90 °C, after the chemical is even, add the finely sifted borneol according to the prescription, stir Mix and transfer to a dropping machine to drip at 80-85 ° C to obtain a small drop pill.

Dissolving the stomach-soluble coating material in water at a ratio of 6 wt% of the weight gain of the coating, fully stirring, and transferring the pill into the coating device at an average inlet air temperature of 85 ° C, an average bed temperature of 35-38 ° C, The coating was carried out under the conditions of an atomization pressure of 2 bar, an average rotation speed of 15 to 23 rpm, and an average material flow rate of 3-4 g/min to obtain a coated pellet.

Finally, the obtained coated pellets were wrapped on a 586 nm yellow plant capsule shell.

Example 13 Small Drop Pill Coated Pills

The pharmaceutical composition was prepared in the same manner as in Example 12, and was coated with a 572 nm green plant capsule shell.

Example 14 Small Drop Pill Coated Pills

The pharmaceutical composition was prepared in the same manner as in Example 12, and the plant capsule shell having a wavelength of 500 nm was coated.

Example 15 Dropping Pill Coated Pills

The pharmaceutical composition was prepared in the same manner as in Example 12, and a 592 nm yellow plant capsule shell was wrapped.

Example 16 Small Drop Pill Coated Pills

The pharmaceutical composition was prepared in the same manner as in Example 12, and the plant capsule shell having a corresponding wavelength of 577 nm was wrapped.

Example 17 Small Drop Pill Coated Pills

The pharmaceutical composition was prepared in the same manner as in Example 12, and the plant capsule shell having a corresponding wavelength of 592 nm was wrapped.

Example 18 Small Drop Pill Coated Pills

The pharmaceutical composition was prepared in the same manner as in Example 12, and wrapped in a 620 nm orange plant capsule shell.

Example 19 Small Drop Pill Coated Pills

The pharmaceutical composition was prepared in the same manner as in Example 12 and wrapped in a 446 nm blue plant capsule shell.

Example 20 Small Drop Pill Coated Pills

The pharmaceutical composition was prepared in the same manner as in Example 12, and was coated with a yellow plant capsule shell of 580 nm.

Example 21 Small Drop Pill Coated Pills

The pharmaceutical composition was prepared in the same manner as in Example 12 and wrapped in a 460 nm blue plant capsule shell.

Example 22 Small Drop Pill Coated Pills

The pharmaceutical composition was prepared in the same manner as in Example 12, and wrapped on a 550 nm green plant capsule shell.

Claims (6)

A capsule preparation made of a drug and a capsule shell, the medicine being filled in the capsule shell; the capsule shell being a yellow capsule shell corresponding to a wavelength range of 577 nm to 592 nm or a green capsule shell of 500 nm to 577 nm The drug is a compound Danshen dripping pill. The capsule preparation of claim 1, wherein the capsule shell is selected from the group consisting of a gelatin capsule shell or a plant capsule shell. The capsule preparation according to claim 1, wherein the compound Danshen dropping pill is a vegetarian pill or a coated pill. For example, in the capsule preparation of claim 1, wherein the compound Danshen dropping pills are made of the following weight percentages of the bulk drug relative to the total weight of the three Chinese herbal medicines: Danshen, Sanqi and Borneol: For example, in the capsule preparation of claim 1, wherein the compound Danshen dropping pills are made of the following weight percentages of the drug substance, relative to the total weight of the three Chinese herbal medicines: Danshen, Sanqi and Borneol: For example, in the capsule preparation of claim 1, wherein the compound Danshen dropping pills are made of the following weight percentages of the drug substance, relative to the total weight of the three Chinese herbal medicines: Danshen, Sanqi and Borneol: The borneol is 0.92%.