WO2014154008A1

WO2014154008A1 - Purgative composition, preparation method therefor and application thereof

Info

Publication number: WO2014154008A1
Application number: PCT/CN2013/090942
Authority: WO
Inventors: 严伟
Original assignee: 成都德实投资管理有限公司
Priority date: 2013-03-26
Filing date: 2013-12-30
Publication date: 2014-10-02
Also published as: CN103142815B; CN103142815A

Abstract

A purgative composition and a preparation method therefor. The composition is prepared by using 4 to 24 parts of mangnolia officinalis, 2 to 15 parts of immature bitter orange, 0.5 to 3 parts of aloe, and 0.5 to 3 parts of angelica by weight.

Description

Laxative composition and preparation method and use thereof

The present invention relates to a laxative composition, a process for its preparation and use.

Background technique

Constipation is a common clinical complex symptom, mainly refers to the reduction of the number of bowel movements, the reduction of feces, the dryness of feces, and the difficulty of defecation. With the changes in people's diet and mental and social factors, the incidence of constipation has increased. The prevalence of constipation in the population is as high as 27%, but only a small number of constipation patients will see you. Constipation can affect people of all ages, women are more than men, and older people are more likely to be younger and younger. Because of the high incidence of constipation and the complex causes, patients often have many distress, and constipation can affect the quality of life when it is severe.

Medical experts believe that constipation is very harmful to human health. Senile constipation is one of the most common clinical syndromes. Constipation is an independent syndrome and often occurs in various acute and chronic diseases. Due to constipation, toxins can not be excreted in time, can cause toxemia, induce intestinal cancer; urgency to earn, can lead to anal fissure, hemorrhoids and other diseases. The influence of constipation on cardiovascular and cerebrovascular diseases has also attracted people's attention. It is often the predisposing factor and lethal factor of acute cardiovascular and cerebrovascular diseases. It can also cause a variety of diseases, such as gallstones, colon cancer, breast cancer, high blood pressure and other diseases. In addition, studies have found that long-term constipation in the elderly can cause dementia. Therefore, research on constipation, early prevention and reasonable treatment of constipation will alleviate the serious consequences and social burden of constipation.

For the treatment of constipation, clinically used stimulant laxatives such as phenolphthalein, senna, and rhubarb are used to treat chronic functional constipation in the elderly. Such drugs stimulate neurons in the intestinal wall to cause an increase in intestinal peristalsis, allowing the contents of the intestine to rapidly advance distally. Long-term use can cause dependence, damage the patient's intestinal nervous system, and is likely to be irreversible. Therefore, it is particularly necessary to provide a safer drug, food or health supplement that treats constipation.

Summary of the invention

It is an object of the present invention to provide a laxative composition. Another object of the present invention is to provide a process for the preparation and use of the composition.

The present invention provides a laxative composition which is prepared from the following weight ratio drug substance:

4~24 parts of Magnolia, 2~15 parts of medlar, 0.5~3 parts of aloe, and 0.5~3 parts of Chinese angelica.

Further, it is a preparation prepared from the following weight ratio raw materials:

4~6 parts of Magnolia, 2~3 parts of medlar, 0.5~1 part of aloe, and 0.5~1 part of Chinese angelica.

Further preferably, it is a preparation prepared from the following weight ratio drug substance: 4 parts of Magnolia Bark, 2.5 parts of medlar, 0-5 parts of aloe vera, and 0.5 part of Angelica sinensis. Wherein, the preparation further comprises 0.5 to 3 parts by weight of an auxiliary material, and the auxiliary material is konjac flour. Further, the amount of konjac flour is 0.5 to 1 part by weight.

Preferably, the konjac flour is used in an amount of 0.5 parts by weight.

Wherein, the composition of the present invention is prepared by the following raw materials of weight ratio: raw materials are: 4 to 24 parts of Magnolia, 2 to 15 parts of medlar, 0.5 to 3 parts of aloe, and 0.5 to 3 parts of Chinese angelica; Excipients are: konjac flour 0.5~3 servings.

Here, the composition is a preparation prepared by using a powder of a drug substance, or a water or an organic solvent extract of a drug substance as an active ingredient, and a pharmaceutically acceptable adjuvant or auxiliary ingredient.

Further, the preparation is an oral preparation.

Further, the oral preparation is a granule, a powder, a tablet, a pill or a capsule. The invention also provides a preparation method of the above-mentioned laxative composition, which comprises the following steps:

(1) Take the magnolia, smash and smash, and after taking the alcohol to form the alcohol, take the supernatant for use;

(2) taking aloe vera, angelica, crushed aloe vera powder, angelica powder;

(3) taking the supernatant of step (1), concentrating or drying, and preparing the preparation together with aloe vera powder and angelica powder, together with pharmaceutically usable adjuvant or auxiliary ingredients.

Further, the specific operation of the water extraction and alcohol precipitation in the step (1) is: after decoction with water, the water decoction is combined and concentrated to the liquid medicine: the original medicine material = l: lml/g, and then the ethanol is added to the ethanol concentration of 70 ~72%, just stand.

The present invention also provides the use of the above-mentioned laxative composition for the preparation of foods, medicines or health care products which soften feces, promote defecation, prevent or treat constipation.

Further, the constipation is non-organic constipation, habitual constipation or intractable constipation.

The laxative composition of the present invention, after combining the single-flavor drugs, exerts a synergistic effect, can enhance intestinal peristalsis, improve intestinal function, soften feces, shorten defecation time, and has better promoting defecation effect. At the same time, no strong diarrhea is used in the composition, which is safer and provides a new choice for preventing or treating constipation.

detailed description

Example 1 Preparation of the laxative composition of the present invention

Prescription:

Ingredients: Magnolia 4g 枳 2. 2. 5g aloe 0. 5g Angelica 0. 5g

Accessories: Konjac flour 0. 5g

Process:

(1) Magnolia, smashed into coarse powder, add 8-12 times water to cook 2 times, each time 1. 5 hours, filter, decoction, concentrate to liquid: original medicine = 1: lml / 。 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30

° Baume, a thick extract. (2) Smash the aloe vera and angelica and pass the 80 mesh sieve.

(3) Mix the thick extract cream, aloe powder, angelica powder, konjac flour, granulate, and dry to obtain dry granules.

(4) Fill the capsules with dry granules, 0. 4g / granules.

The konjac flour used in the present invention all conforms to the provisions of GB/T 18104-2000, and may be a special grade, primary or secondary product. Example 2 Preparation of the laxative composition of the present invention

(1) Take 20g of Magnolia, 12g of medlar, boil 3 times with water, 30min each time, combine the extracts for use;

(2) Take 2g of aloe vera, 2g of angelica, crush, and pass through 80 mesh sieve;

(3) Take the extract, concentrate, add aloe powder, angelica powder and 2g konjac flour, mix, dry, pulverize, granulate, that is, granules. Example 3 Preparation of the laxative composition of the present invention

Take Magnolia 4g, eucalyptus 15g, Aloe 3g, Angelica 3g, add water for 3 times, each time for 30min, combine water decoction, concentrate, add 3g konjac flour and appropriate amount of soluble starch and dextrin, granulate, Dry, that is, granules. Example 4 Preparation of the laxative composition of the present invention

Take 6g of Magnolia, 2g of citrus aurantium, 0.5g of aloe vera, 0.5g of Angelica, 0.5 times of reflux with 70% ethanol, and combine the alcohol extract; the slag is boiled twice with water, combined with decoction; After extracting ethanol from alcohol extract , mixed with decoction, concentrated to dryness, adding 0.5g konjac flour and appropriate amount of dextrin, granulating, tableting, that is, tablets. Example 5 Preparation of the laxative composition of the present invention

Prescription:

Ingredients: Magnolia 400g 枳 250g aloe 60g Angelica 60g

Accessories: Konjac Fine Powder 80g

Process:

(1) Magnolia, citrus, and angelica are pulverized into coarse powder, and boiled for 3 times with water, each time 0.5 hours, filtered, and decoction is used;

(2) Smash the aloe vera and pass the 80 mesh sieve.

The granules are filled with aloe vera powder, and the konjac powder is mixed, spray-dried, and the dry granules are filled into capsules, 0.4 g/granules. The beneficial effects of the present invention will be specifically described below by way of test examples.

Test Example 1 Experimental study on the efficacy of the composition of the present invention

1 effect on intestinal function of mice

1. 1 Principle of experiment

Diphenoxylate is a derivative of meperidine and is a synthetic antidiarrheal. It converges and reduces intestinal peristalsis, which causes the stool to dry and form constipation. After the drug is administered to the mice, the intestinal tension can be increased, the intestinal peristalsis can be inhibited, and the intestinal absorption of water can be increased, resulting in a decrease in bowel movements or difficulty in defecation, thereby causing constipation in the intestines. Therefore, this experiment utilizes the specific pharmacological effects of diphenoxylate to simulate the pathological changes of clinical constipation, and is simple and easy. Therefore, it is an ideal animal constipation model worthy of application.

The mice were intragastrically administered with diphenoxylate as a model drug, and a mouse constipation model was established to reflect the mouse's first black urinary time, the number of defecation grains and the water content of the feces in 5 or 6 hours. Defecation.

1. 2 experimental animals

Adult male adult mice (20 ± 2 g) were used, with 10 in each group.

1. 3 Reagents and drugs

Activated carbon, gum arabic, distilled water, compound diphenoxylate, phenolphthalein

1. 4 reagent configuration

Ink: Acacia 100g, add 800ml distilled water, boil to transparent, weigh 50g of active charcoal powder, add to boil three times, let stand, cool down, dilute to 1000ml, shake well before use.

Compound diphenoxylate solution at a concentration of 0.05%: 20 tablets (50 mg) of compound diphenoxylate tablets, dissolved in water after pulverization, and made up to 100 ml.

1. 5 Experimental process

1. 5. 1 experimental grouping

Blank control group: only distilled water

Model control group: modeled with compound diphenoxylate

Positive drug control group: fruit guide film 0. 01g / kg gavage

test group:

The capsule contents prepared in Example 1 were each divided into a low dose (adult 10 times dose) group, a medium dose (20 times dose for adults) group, and a high dose (30 dose for adults) group.

The Magnolia group, the medlar group, the Angelica group, the Magnolia sinensis group, and the Aloe konjac flour (1:1) group were prepared according to the corresponding ratio and method of Example 1. The dosage is shown in Table 1.

1. 5. 2 experimental steps

1. 5. 2. 1 modeling

In the experimental mice, the compound diphenoxylate 40~50mg/kg was administered, and the number of defecation particles was reduced and the defecation time was prolonged, that is, the modeling was successful. 1. 5. 2. 2 gavage

The blank control group and the model control group were given distilled water only. The positive group was intragastrically administered at 0.01 g/kg, and the experimental group was intragastrically administered in the low dose group, the middle dose group and the high dose group. 4毫升。 Each of the drugs were administered twice a day, 8 hours apart, each dose of 0. 4ml. Seven days later, mice in each group were fasted for 16 hours. The control group was given distilled water, and the other groups were given 0.01 mg/kg of compound diphenoxylate. After 0.5 h, the blank control group and the model control group were given ink, and the other 4 groups were given drugs with ink.

Start the timer after filling the ink, record the time of the first blackout of each mouse, the number of particles in the defecation and the moisture content of the feces, and the water content = (the total weight of the feces and the weight of the feces after drying) X 100% / total feces weight.

1. 6 Analysis of experimental results

1. 6. 1 The mice in each experimental group had normal diet and activities, and the feces were granular and there was no diarrhea.

1. 6. 2 The experimental data obtained were compared by means of analysis of variance for the degree of significant difference between the groups.

Table 1 Timeline for the first blackout of each drug dose mouse (min)

Note: Compared with the blank control group, *ρ<0.05, **ρ<0. 01; compared with the constipation model group: Ap<0.05, Table 2 Five-hour defecation number (grain) and Fecal water

Low-dose control group 0.345 10 14.50±1.71 ^ΛΛ 45.44±4.81 ^ΛΛ middle dose control group 0.690 10 15.00±1.92 ^ΛΛ 46.32 ±4.63* ^ΛΛ high-dose control group 1.035 10 16.40 ±1.84 ^WAA 46.51 ±5.15" ^{ΛΛ 朴组} group 1.71 10 12.10 ±1.98 37.68 ±5.80 枳实组1.07 10 11.96 + 2.05 37.33±5.87 Aloe Vera + Konjac Fine Powder Group 0.375 10 12.06±2.34 39.47 ±5.07 Aloe Vera + Konjac ^Fine Powder Group 0.75 10 14.50±1.71 ^ΛΛ 45.44±4.81 ^{ΛΛ 归组} Group 0.345 10 11.94±1.67 38.05 ±4.61 Houpu Shizheng group 2.78 10 12.37±2.35 ^Λ 39.37±5.07 Note: Compared with the blank control group, *ρ<0.05, **ρ<0.01; compared with the constipation model group: Ap<0.05, from the table 1, 2 can be seen:

(1) The composition of the present invention can significantly shorten the defecation time, increase the stool volume, and promote the softening effect of the mouse.

(2) The composition of the present invention has a more defecation effect in the case of less than or equal to the dose of each single-drug drug, indicating that the combination of the drugs in the present invention has a laxative effect superior to each component, thereby exerting synergy. Synergies.

2 small intestine charcoal propulsion experiment

2.1 Experimental principle

The function of the small intestine of the mouse is examined, and the usual method is to measure the ink promotion rate of the small intestine at a certain time. The method used in this experiment was to establish a mouse peristalsis inhibition model by modeling with compound diphenoxylate, and then to measure the ink propulsion rate of the small intestine of the mice after administration. This indicator measures the intestinal function of mice.

2.2 Experimental animals

Adult male adult mice (20 ± 2 g) were used, with 10 in each group, a total of 60 rats.

2.3 Reagents and drugs

2.4 Reagent configuration

Ink: Gum arabic 100g, add 800ml distilled water, boil to transparent, weigh 50g of active charcoal powder, add to boil three times, let stand, cool down, dilute to 1000ml, shake well before use.

Compound diphenoxylate solution at a concentration of 0.05%: 20 tablets (50 mg) of compound diphenoxylate tablets, pulverized, dissolved in water, and made up to 100 ml.

2.5 Experimental process

2.5.1 Experimental grouping Blank control group: only distilled water

Model control group: modeled with compound diphenoxylate

Positive drug control group: fruit guide film 0. 01g / kg gavage

Experimental group: The capsule contents prepared in Example 1 were each divided into a low dose (adult 10 times dose) group, a medium dose (20 times dose for adults) group, and a high dose (30 times dose for adults) group. 2. 5. 2 Experimental steps

2. 5. 2. 1 Modeling

In the experimental mice, the compound diphenoxylate 40~50mg/kg was administered, and the number of defecation particles decreased, and the defecation time was prolonged, that is, the modeling was successful.

2. 5. 2. 2 gavage

The blank control group and the model control group were given distilled water only. The positive drug control group was administered with 0.01 g/kg, and the experimental group was administered with low dose group, medium dose group and high dose group. 4毫升。 Each of the drugs were administered twice a day, 8 hours apart, each dose of 0. 4ml. Seven days later, mice in each group were fasted for 16 hours. The blank control group was given distilled water, and the other groups were given 0.01 mg/kg of compound diphenoxylate. After 0.5 h, the blank control group and the model control group were given ink, and the other 4 groups were given drugs with ink. After the ink is filled, the time is started. Immediately after 25 minutes, the mice are removed from the cervical vertebrae, the peritoneum is opened by the abdominal cavity, and the upper part is removed from the pylorus (total length).

Measure the total length of the small intestine, ie the upper part of the small intestine to the pylorus, and the length of the ink advancement, ie from the pylorus to the ink, calculate the ink advancement rate as follows:

Ink advance rate (%) = ink advancement length (cm) / total length of small intestine (cm) X 100%

2. 6 Analysis of experimental results

The mice in each experimental group had normal diet and activities, and the feces were granular and there was no diarrhea.

Table 3 Ink propulsion rate of mice in each drug dosage group

Note: Compared with the blank control group, *p<0.05, **p<0. 01; compared with the constipation model group: Ap<0.05, as can be seen from Table 3, the low and medium dose group ink propulsion rate Compared with the model control group, it reached a very significant level, which was comparable to the blank control group and lower than the positive drug control group. The high dose group was higher than the model control group and the blank control group, reaching a very significant level, slightly higher than the positive drug control group. . Description of the combination of the invention The substance can enhance intestinal peristalsis and improve intestinal function.

3 constipation model mouse small intestine water content experiment

3. 1 Principle of experiment

The mice were intragastrically administered with compound diphenoxylate as a model drug, and a mouse constipation model was established. The water content of the mouse small intestine was calculated by measuring the weight of the small intestine of the mouse and the weight of the small intestine of the mouse after drying.

3. 2 experimental animals

3. 3 Reagents and drugs

3. 4 reagent configuration

3. 5 Experimental process

3. 5. 1 experimental grouping

1. Blank control group: only distilled water

2. Model control group: Modeling with compound diphenoxylate

3, positive drug control group: fruit guide tablets 0. 01g / kg gavage

4. Experimental group: The capsule contents prepared in Example 1 were all divided into a low dose (adult 10 times dose) group, a medium dose (20 times dose for adults) group, and a high dose (30 times dose for adults) group.

3. 5. 2 Experimental steps

3. 5. 2. 1 Modeling

In the experimental mice, the compound diphenoxylate 40~50mg/kg was administered, and the number of defecation particles in the animals decreased, and the time was prolonged, that is, the modeling was successful.

3. 5. 2. 2 gavage

1. The blank control group and the model control group were given only distilled water. The positive group was intragastrically administered with 0.01 g/kg, and the experimental group was administered with low dose group, medium dose group and high dose group. 4毫升。 Each of the drugs were administered twice a day, 8 hours apart, each dose of 0. 4ml.

2. After seven days, each group of mice was fasted for 16 hours.

3. The blank control group was given distilled water, and the other groups were given 0.11 g/kg of compound diphenoxylate.

After 4, 0. 5h, the blank control group and the model control group were given ink, and the other 4 groups were given drugs with ink. 5, 2h after the death, ligation from the upper end of the pylorus, cut the intestine, ligature with the upper end of the ileocecal section, cut the intestine, remove the small intestine. The wet weight of the small intestine was weighed with a balance, recorded, and then the small intestine was placed in an oven, dried at 80 ° C to constant weight, and recorded, and the moisture content of the small intestine was calculated according to the formula.

Intestinal water content (%) = (small intestine wet weight - small intestine dry weight) / small intestine wet weight X 100%

3. 5. 3 Analysis of experimental results

Table 4 Small intestine water content of mice in each drug dosage group

Note: Compared with the blank control group, <0.05, V0. 01; compared with the constipation model group: ^Δ ρ<0. 05, ^ΔΔ ρ<0. 01 From Table 4, the intestinal water content of the three dose groups It was higher than the model control group and reached a very significant level; the water content of the small intestine in the three dose groups was basically the same as that in the blank control group and the positive drug control group. That is, the three dose groups can restore the intestinal water content of the constipation model mice to normal levels. In summary, the laxative composition of the present invention, after combining the single-flavor drugs, exerts a synergistic effect, can enhance intestinal peristalsis, improve intestinal function, soften feces, shorten defecation time, and has better It promotes defecation. At the same time, it does not use strong diarrhea drugs in the composition, which is safer and provides a new choice for preventing or treating constipation. INDUSTRIAL APPLICABILITY The laxative composition of the present invention, when used in combination with each single-flavored drug, exerts a synergistic effect, can enhance intestinal peristalsis, improve intestinal function, soften stool, shorten defecation time, and has better It promotes defecation. At the same time, it does not use strong diarrhea drugs in the composition, which is safer. It provides a new choice for preventing or treating constipation, and is suitable for industrial application.

Claims

claims

1. A laxative composition, characterized in that: it is a preparation prepared from raw materials with the following weight ratio:

4 to 24 parts of Magnolia officinalis, 2 to 15 parts of Citrus aurantium, 0.5 to 3 parts of aloe vera, and 0.5 to 3 parts of Angelica sinensis.

2. The laxative composition according to claim 1, characterized in that: it is a preparation prepared from raw materials with the following weight ratio:

4 to 6 parts of Magnolia officinalis, 2 to 3 parts of Citrus aurantium, 0.5 to 1 part of aloe vera, and 0.5 to 1 part of Angelica sinensis.

3. The laxative composition according to claim 1, characterized in that: it is a preparation prepared from raw materials with the following weight ratio:

4 parts of magnolia bark, 2.5 parts of citrus aurantium, 0.5 parts of aloe vera, and 0.5 parts of angelica root.

4. The laxative composition according to any one of claims 1 to 3, characterized in that: the preparation also includes 0.5 to 3 parts by weight of auxiliary materials, and the auxiliary materials are konjac powder.

5. The laxative composition according to claim 4, characterized in that: the dosage of konjac powder is 0.5-1 parts by weight.

6. The laxative composition according to claim 5, characterized in that: the dosage of konjac powder is 0.5 parts by weight.

7. The laxative composition according to any one of claims 1 to 6, characterized in that: the preparation is an oral preparation.

8. The preparation method of the laxative composition according to any one of claims 1 to 7, characterized in that: it includes the following steps:

(1) Crush Magnolia officinalis and Citrus aurantium, and after water extraction and alcohol precipitation, take the supernatant and set aside;

(2) Take aloe vera and angelica root and crush them to obtain aloe vera powder and angelica root powder;

(3) Take the supernatant from step (1), concentrate or dry it, and prepare a preparation together with aloe vera powder and angelica powder, together with pharmaceutically available excipients or auxiliary ingredients.

9. The preparation method according to claim 8, characterized in that: the specific operation of the water extraction and alcohol precipitation in step (1) is: after adding water to decoct, combine the water decoctions, and concentrate to the medicinal solution: original medicinal materials = 1 :lml/g, then add ethanol until the ethanol concentration is 70~72%, and let it stand.

10. Use of the laxative composition according to any one of claims 1 to 7 in the preparation of foods, medicines or health care products for softening feces, promoting defecation, preventing or treating constipation.

11. The use according to claim 10, characterized in that: the constipation is non-organic constipation, habitual constipation or refractory constipation.