CN105582485A

CN105582485A - Phenolphthalein tablets for treating constipation and preparation method thereof

Info

Publication number: CN105582485A
Application number: CN201610142487.6A
Authority: CN
Inventors: 林凡儒; 聂昌盛; 罗小倩; 毛传伟
Original assignee: SHANDONG KERNEL AND HALL PHARMACEUTICAL INDUSTRY Co Ltd
Current assignee: Tong Ren Pharmaceutical Co., Ltd.
Priority date: 2016-03-14
Filing date: 2016-03-14
Publication date: 2016-05-18

Abstract

The invention relates to phenolphthalein tablets for treating constipation and a preparation method thereof. The phenolphthalein tablets are prepared from phenolphthalein, active ingredients of traditional Chinese medicine, starch, 10% starch slurry, magnesium stearate and sodium dodecyl sulfate; the raw materials are taken, granulation is performed according to a conventional method, and five hundred thousand tablets are prepared. The phenolphthalein tablets are remarkable in constipation curative effect, treat both symptoms and root causes and have the wide application prospect.

Description

Be used for the treatment of phenolphthalein sheet of constipation and preparation method thereof

Technical field

The invention belongs to medical technical field, be specifically related to a kind of phenolphthalein sheet and preparation technology thereof who is used for the treatment of constipation.

Background technology

Along with the change of dietary structure and the interference of psychologic factors, constipation has become affects one of key factor of modern's quality of life. But at present clinical be that disease or the concept of disease are more chaotic about constipation, in International Classification of Diseases, " constipation " is a kind of sick, Domestic Medicine circle is to have multiple viewpoint in disease or the problem of disease about " constipation ", lacks unified understanding, so that researcher or clinician are at a loss as to what to do.

Constipation is a difficulty and complicated clinical problem, along with the fast development of modern science and technology in recent years, and with the continuous combination of modern medicine, medical circle has had significant progress to the understanding of constipation, particularly irradiation image is learned a skill and introduce after the research of constipation, produced qualitative leap, established the primary condition that constipation is sick and constipation possesses separately, be described below: the primary condition of establishing constipation disease: 1. have clear and definite sick position, sick position is at large intestine; 2. have clear and definite pathogenesis, basic pathology is that Colonic transit is slowly with outlet obstructed; 3. there is one group of distinctive symptom, sign and laboratory examination results, as: just time reduce, dry and hard, the awareness of defecation of excrement matter disappearance; Other features such as x-ray barium meal characteristic feature " gooseneck boom is levied ", " shelf is levied ", " intussusception in rectal mucosa "; 4. there are clear and definite diagnostic criteria and discrimination method; 5. can propose somatotype, classification, by stages, calibration etc. Establishing constipated primary condition has: 1. some is without the functional consitipation of organic disorder, and patient lacks defecation physiology general knowledge, thereby has destroyed normal defecation physiology conditioned reflex, as: be late for defecation, long term inhibition awareness of defecation; 2. the constipation that has clear and definite primary disease to occur together: (1) phrenoblabia constipation induced, as depression, mental disease, anorexia nervosa; (2) iatrogenic constipation, as codeine, morphine, antidepressant, anticholinergic preparation, chalybeate, braking etc. 3. the constipation that Nonorganic lesion causes, constipation in a year " course of disease " is less than 3 months. These are all symptomatic constipation, easily differentiate mutually with constipation disease. In sum, there is the symptom of constipation, and can be by the organic disorder of iconography and the relevant intestines passage of laboratory diagnosis discovery or adjacent organs, through 3 months above invalid or unsatisfactory curative effects of regular medicine treatment, or need long-term adopt that medicine, gimmick, apparatus help defecation can be diagnosed as constipation disease. And primary disease is clear and definite, often be secondary to the other diseases outside intestines passage, or because the treatment medicine of other diseases and the apparatus of use cause, by iconography and laboratory diagnosis without relevant organic disorder, after curing primary disease or removing above factor, constipation can be alleviated or eliminate, and can be diagnosed as constipation. In other words, the patient of constipation disease necessarily has constipation symptom, but not every constipation can be diagnosed as constipation disease. Once constipation has caused the organic disorder of relevant intestines passage or adjacent organs, just develops into constipation disease. Certainly constipation is sick through effectively treatment, the relevant intestines passage of check or adjacent organs do not have organic abnormal again, still has constipation, and constipation has now been only just a symptom.

The pathogenesis of constipation: food is after digesting and assimilating, the remaining chyme residue that can not absorb once again drains into colon with enterocinesia by small intestine, colonic mucosa further absorbs moisture and electrolyte again, and ight soil generally progressively forms in transverse colon, finally transports and reaches colon, rectum. Rectal mucosa is subject to the mechanical irritation of the full expansion of ight soil, sensigenous impulsion, impulsion is imported cerebral cortex into through pelvic cavity nerve, waist sacral spinal cord, through efferent nerve, impulsion is reached to rectum again, rectum muscle is shunk, Sphincter ani chalasia, and then abdominal muscle and diaphram shrink simultaneously ight soil are excreted from anus. Below be normal defecation reflex process. If all can cause constipation when obstacle appears in any one link of this defecation reflex process. Following factor is all that the major reason of constipation occurs: 1. food or the hypohydration taken in, and make the amount of chyme residue in intestines or ight soil also few, be not enough to stimulate the normal creepage of gastrointestinal functions of colon; 2. the wriggle weakness of enteron aisle or enteron aisle muscle tone lower; 3. enteric cavity has narrow or blocks existence, and normal enterocinesia is obstructed, and causes the ight soil can not the row of descending, for example intestinal obstruction or proportion of cancer of left side of colon. 4. when any link has obstacle or pathology in defecation reflex process, all can there is constipation, for example decreased sensation of rectal mucosa mechanical irritation, pelvic cavity nerve, waist sacral spinal cord DPN, sphincterismus, abdominal muscle and contraction of diaphragm hypomotility etc.

Motherland's medical science, about the discussion of constipation, sees Huangdi's Internal Classics the earliest, has set forth disease damage position, the cause of disease, relevant internal organs and the clinical symptoms of constipation, is a kind of disease but do not explicitly point out it. The discussion of the aspects such as the symptom of doctor's later age to constipation, diagnosis, dialectical, treatment all has performance, have using it as one independently disease discuss, what have is only used as it as a symptom, lacks so far unified understanding. In the existing textbook of College of Chinese Medicine " Chinese Internal Medicine ", think: " constipation refers to because large intestine conduction is not normal, causes constipation, defecation cycle stretch-out; Or the cycle is not long, but excrement matter is dry and hard, and it is difficult to discharge; Or excrement matter is not hard, though have awareness of defecation, just and not smooth disease ". Infer accordingly, the constipation that this section discussed is mainly to occur with the concept of symptom. But next this section is divided into constipation again real secret (stomach accumulated heat, depression and stagnation of QI, cold sensation of the genitalia stagnate) and empty secret (deficiency of vital energy, the deficiency of blood, the deficiency of Yin, the deficiency of yang) two large class seven card types, occurred more detailed differentiation of symptoms and signs for classification of syndrome, " constipation " discussed has here been obviously disease instead of " symptom ". In the discussion of a same section, sick still fuzzy with the concept of disease. National Standard of the People's Republic of China's " tcm clinical practice diagnosis and treatment term disease part " compiles and edits 930 of disease terms (not comprising Bone injury disease) altogether, 49 of symptomatic terms, by clear and definite constipation belonging in symptomatic term, think that constipation is a kind of symptom. And the traditional Chinese medical science monograph of recent publication is listed in the status equal with other anal and intestinal diseases with chapters and sections independently by constipation, and independently sick kind is from aspect expansion discussions such as etiology and pathology, clinical manifestation, laboratory examination, diagnosis and discriminating, treatment and prognosis, visible far beyond the category of symptom as one. At present, constipation is divided into following Four types by the traditional Chinese medical science: 1. stomach dryness-heat type: pungent thick the hiding of overfeeding, and cross the product etc. that take temperature compensation and can cause the overabundance of yang and burn cloudy; After pyreticosis, waste heat is reluctant to leave stomach, and consumption is hindered body fluid; Or damp invasion of lower energizer large intestine, make enteron aisle scorching, hinder Tianjin and constipation, it is secret that this constipation is called again heat. 2. depression and stagnation of QI type: feelings will is not relaxed, sorrow ponders over, sitting less moving, prolonged illness bed etc. cause depression and stagnation of QI, cause in large intestine conduction dereliction of duty, waste matter and stop, form constipated, i.e. so-called " in gas stagnant and thing is not all right ". 3. type of deficiency of both blood and body fluid: prolonged illness, postpartum, old body decline, qi-blood deficiency; Taste internal injury, amount of drinking water are few, and change source deficiency, is rushed down lower impairment of yin etc. at too sweating in disease. The deficiency of vital energy large intestine is passed on unablely, and blood deficiency and depleted fluid large intestine moistens to lose and supports, and makes enteron aisle dry withered, just go involved and abstruse, so be called empty secret. 4. yang deficiency of spleen and stomache: year high prolonged illness, kidney-yang deficiency, yang-energy is not transported cloudy heresy and is condensed; Or have spleen YANG deficiency, and sent an expedition against by cold, decline and cause spleen kidney yang, Wen Zhao haves no right cold obstruction causing qi stagnation, and enteron aisle transmits unable, and difficulty in defecation, is called constipation due to endogenous cold.

At present, constantly have clinically the medicine (comprising Western medicine and Chinese medicine) of the habitual intractable constipation of new treatment to occur, but these all fail to reach real gratifying effect. The Chinese and Western medicine compound drug of develop a kind of high-efficiency low-toxicity, treating both principal and secondary aspect of disease is still clinical eager needs.

Summary of the invention

The object of this invention is to provide a kind ofly treat both principal and secondary aspect of disease, side effect is little, the Chinese and Western medicine compound preparation of safe ready. Its objective is in order to solve treatment constipation, overcome Western medicine side effect, drug withdrawal problem repeatedly, reach the object for the treatment of both principal and secondary aspect of disease.

Present inventor is according to forefathers' experience and oneself medical practice for many years, and by the research to traditional Chinese medicine, the network of focusing on internal organs channels and collaterals belongs to, adjoins, the treatment of progress of disease relation. From motherland's medical treasure-house, filter out the natural traditional Chinese medicine that the place that clears away heart-fire is tired of, relaxes bowel, by theory of traditional Chinese medical science prescription, skim the cream off milk, the effect that make its performance heat-clearing, nourishes blood, moisturizes laxation, adopt natural Chinese traditional medicines raw material, be meticulously mixed with the Chinese medicine composition for the treatment of constipation of the present invention in conjunction with Traditional Chinese Medicine technology, constipation is had to effect of rapid healing.

For achieving the above object, the technical solution used in the present invention is as follows:

The phenolphthalein sheet that is used for the treatment of constipation, it is prepared and is obtained by following raw material:

Phenolphthalein 50kg, starch 25kg, 10%(part by weight) starch slurry 20kg, dolomol 0.77kg, dodecyl sodium sulfate 0.23kg

Get above-mentioned raw materials, according to conventional method granulation, prepare 500,000, tablet.

Preferably, described in be used for the treatment of the phenolphthalein sheet of constipation, it is prepared and is obtained by following raw material:

Phenolphthalein 18kg, active ingredient of Chinese herbs 25kg, starch 25kg, 10%(part by weight) starch slurry 22kg, dolomol 0.77kg, dodecyl sodium sulfate 0.23kg

Described active ingredient of Chinese herbs, is obtained by the raw material preparation of following weight:

35 parts of saline cistanches, 35 parts of the shell of areca nuts, 35 parts of cassia seeds, 35 parts of dandelions, 35 parts, almond,

30 parts of 30 parts of the fruit of glossy privets, mulberries, 30 parts of root tubers of aromatic turmeric, 30 parts of Snakegourd Fruits, 30 parts of the dried immature fruit of citron oranges,

25 parts of sweet wormwoods, 25 parts of great burdock achenes, 25 parts of golden cypresses, 25 parts of the tubers of stemona, 25 parts of Radix Angelicae Sinensis,

20 parts of dried orange peels, 20 parts of polygala roots, 20 parts of myrrhs, 20 parts of Ligusticum wallichiis, 20 parts, Poria cocos,

15 parts, Radix Glycyrrhizae, 10 parts of Chinese yams, 10 parts, peach kernel.

The preparation method of described active ingredient of Chinese herbs is:

(1) take above-mentioned raw materials for subsequent use;

(2) depend on pine torch, almond, the fruit of glossy privet, Snakegourd Fruit, the dried immature fruit of citron orange, great burdock achene, Radix Angelicae Sinensis, dried orange peel, myrrh, Chinese yam, peach kernel boiling, add for the first time 3 times of weight water, decoct 1 hour, after filtration, obtain filtrate and the dregs of a decoction, the dregs of a decoction are added to 2 times of weight decoctings and boil half an hour, after filtering, obtain filtrate, merge filtrate twice, filtrate after merging is condensed into the medicinal extract that density is 1.2g/ml, 60 DEG C dry after, pulverize and obtain composite I;

(3) get surplus stock and add 3 times of weight 75%(volume ratios) ethanol, refluxing extraction 2 times, each 1 hour, extract merged, and is concentrated into the medicinal extract that density is 1.2g/ml, 60 DEG C dry after, pulverize and obtain Complex II;

(4) evenly mixed complex I and Complex II obtain active ingredient of Chinese herbs.

Pharmaceutical composition of the present invention has the place's effect of being tired of, relaxing bowel that clears away heart-fire, and clinical practice proves, evident in efficacy to the especially habitual intractable constipation of constipation, efficient height.

Detailed description of the invention

Embodiment 1

Embodiment 2

15 parts, Radix Glycyrrhizae, 10 parts of Chinese yams, 10 parts, peach kernel.

The preparation method of described active ingredient of Chinese herbs is:

(1) take above-mentioned raw materials for subsequent use

The pharmacodynamics test of pharmaceutical composition prepared by embodiment 2, use Constipation Model to carry out the experiment of normal mouse defecation, intestinal contents Promoting Experiment (small intestine movement of mice propelling method, atropine load mouse bowel movement Disorder Model, normal rat large intestine propelling method), enteron aisle moisture absorption experiment (experiment of normal mouse enteron aisle moisture absorption, the experiment of intestine in rats moisture), in vitro cavy intestinal tube smooth muscle experiment etc., observe the preventive and therapeutic effect of tested material soft capsule on Constipation Model and in body and intestine in vitro, impact on intestine and small intestine moisture absorption. Result of the test shows:

1, mice with constipation is had to laxative defecating feces excretion: tested material has stronger functions of loosening bowel relieving constipation to the uninteresting knot in Tianjin, real hot constipation and non-specific mice with constipation, can shorten to some extent defecation time for the first time, increase mouse feces volume, and can soften stool, increase defecation sum and increase ight soil water content (p < 0.05, p < 0.01). Above-mentioned Constipation Model mouse gives after tested material institute's bowel movement taking soft stool and semiliquid stool as main, and ight soil is shaped, soft expanding in the majority.

2, normal mouse is had to the smooth defecating feces excretion of profit: tested material can obviously shorten normal mouse defecation time for the first time after administration 1h, defecation grain number increases, and ight soil water content increases (p < 0.05, p < 0.01). Normal mouse gives after tested material institute's bowel movement taking soft stool and semiliquid stool as main, and ight soil is shaped, soft expanding in the majority. Tested material high dose group mouse stool is most for being shaped or shapeless, thick semiliquid stool, just minority is scattered paste shape or rare as water liquid.

3, reduce the absorption of enteron aisle moisture: tested material can suppress normal size mouse moisture absorption, increase intestinal tube water content, play the effect (p < 0.05, p < 0.01) of softening stool.

Embodiment 3

Acute toxicity testing: 60 of application mouse, male and female half and half, body weight 30～40g, carries out acute toxicity test. Mouse is divided into two groups at random, be 1 group of control group and embodiment, 2 groups of embodiment, 20 every group, fasting 12 hours before experiment, administration group gives respectively pharmaceutical composition prepared by embodiments of the invention 1, embodiment 2 and is dissolved in gastric infusion in water, control group gives equivalent physiological saline, administration in a day 2 times, delivery time 6 hours, Continuous Observation fortnight after administration, and record mouse toxic reaction and death toll. Experimental result shows: with control group comparison, after administration, mouse has no notable difference, experiment Continuous Observation two weeks, and mouse overall health of patients, diet, drinking-water, body weight gain are all normal. Therefore pharmaceutical composition toxicity of the present invention is lower, and clinical application is comparatively safe.

Embodiment 4

Clinical data

Choose at random 136 intractable constipation patients, wherein 68 of men, 68 of female, age 46-73 year, average course of disease 3 years. Symptom: defecation time extends, and 3 days with the last time, ight soil dry, hard. Patient is equally divided into 2 groups according to age, sex, the ill time limit and constipation situation, 1 group of 68 people of embodiment, 2 group of 68 people of embodiment, there was no significant difference between two groups.

Methods for the treatment of:

1 group of embodiment gives pharmaceutical composition prepared by embodiment 1, be grown up one time 1/2 ~ 2;

2 groups of embodiment give pharmaceutical composition prepared by embodiment 2, be grown up one time 1/2 ~ 2.

The classification of constipation symptom

I level: stool 2-3 day separates, dry;

II level: stool 5-7 day separates, dry, abdominal distension, stool time lengthening;

III level: defecate and do not understand for tens days, abdominal distension severity, the full dry reality of ruffian, flushing rough, halitosis, thirsty, abdomen examination is visible intestines shape sometimes, and companion sees hemorrhoid, anal fissure, prolapse of the anus, pelvic cavity extravasated blood syndrome etc.

Criterion of therapeutical effect

Effective: free movement of the bowels, within two days, once just matter turns profit, and unobstructed when solution, short-term is without recurrence;

Effective: within 3 days, with interior defecation, just matter turns profit, it is smooth that defecation is owed;

Invalid: constipation is not improved.

Result for the treatment of is in table 1

Table 1 liang group result for the treatment of

Group	Number of cases	Effective	Effectively	Invalid	Total effective rate
						1 group of embodiment	68	34	20	14	79.4%
2 groups of embodiment	68	50	13	5	92.6%

The phenolphthalein sheet of the application's treatment constipation is with low cost, evident in efficacy, has broad application prospects.

Claims

1. be used for the treatment of the phenolphthalein sheet of constipation, it obtains according to following technique preparation:

Get phenolphthalein 50kg, starch 25kg, 10%(part by weight) starch slurry 20kg, dolomol 0.77kg, dodecyl sodium sulfate 0.23kg, according to conventional method granulation, prepares 500,000, tablet.

2. be used for the treatment of the phenolphthalein sheet of constipation, it obtains according to following technique preparation:

Get phenolphthalein 18kg, active ingredient of Chinese herbs 25kg, starch 25kg, 10%(part by weight) starch slurry 22kg, dolomol 0.77kg, dodecyl sodium sulfate 0.23kg, according to conventional method granulation, prepares 500,000, tablet.

3. according to the phenolphthalein sheet described in claim 1-2, it is characterized in that, described active ingredient of Chinese herbs is obtained by the raw material preparation of following weight parts:

15 parts, Radix Glycyrrhizae, 10 parts of Chinese yams, 10 parts, peach kernel.

4. according to the pharmaceutical composition described in claim 1-3, it is characterized in that, the preparation method of described active ingredient of Chinese herbs is:

(1) take each raw material for standby;

(2) depend on pine torch, almond, the fruit of glossy privet, Snakegourd Fruit, the dried immature fruit of citron orange, great burdock achene, Radix Angelicae Sinensis, dried orange peel, myrrh, Chinese yam, peach kernel, mix, boiling, adds 3 times of weight water for the first time, decoct 1 hour, after filtration, obtain filtrate and the dregs of a decoction, the dregs of a decoction are added to 2 times of weight decoctings and boil half an hour, after filtering, obtain filtrate, merge filtrate twice, filtrate after merging is condensed into the medicinal extract that density is 1.2g/ml, 60 DEG C dry after, pulverize and obtain composite I;

(3) get surplus stock and mix, adds 3 times of weight 75%(volume ratios) ethanol, refluxing extraction 2 times, each 1 hour, extract merged, and is concentrated into the medicinal extract that density is 1.2g/ml, 60 DEG C dry after, pulverize acquisition Complex II;

(4) evenly mixed complex I and Complex II and get final product.

5. the purposes of pharmaceutical composition described in claim 1-4.