Oral preparation capable of enriching yin and moistening intestines
The present invention relates to treat the oral formulations of constipation, specifically is to be raw material with the Chinese medicine Radix Rehmanniae, and the oral medicine through special process is prepared from has loosening bowel to relieve constipation, adjusts the effect of intestinal microbial population, belongs to the field of Chinese medicines.
Constipation is common, frequently-occurring disease, and along with the modern civilization progress, people's dietary structure changes, rhythm of life is accelerated, and reason such as the aging of population, and the crowd of constipation increases.
Constipation is not a serious disease, but healthhazard is not little.Constipation can cause or increase the weight of anorectum diseases such as proctitis, anal fissure, hemorrhoid and fecal ulcer; Cause eccentricity diarrhoea, RAP etc.Harmful metabolite ammonia, phenol, H in the chronic constipation, body
2To such an extent as to S carcinogenic activity product is stranded in intestinal for a long time, be absorbed into blood, then cause the digestive tract function disorder, inappetence, abdominal part distension and headache, dizziness, fatigue and weak, General Symptoms such as fidgety, and cause or increase the weight of some systemic disease, bring out or increase the weight of cardiac insufficiency, coronary ischemia and arrhythmia, cardiogenic shock, heartbeat all standing, cause sudden death.Serious constipation person even can cause colorectal cancer.Therefore very important for the treatment of constipation.For the treatment of constipation, medicine is a lot of clinically at present, but these relieving constipation medicine life-time service all have its untoward reaction, for example:
1, irritant laxative
Past one is to thinking that irritant laxative is to cause directly or by the excited intestinal smooth muscle of nervous pathway to rush down down, discovered that over the past two decades some diarrhea inducing are from the body active substance, as prostaglandin, leukotriene, 5 hydroxyl ten or twenty carbon tetraenoic acids, 5-hydroxyl peroxidating eicosatetraenoic acid, 5-hydroxy tryptamine, P material, Kallidin I and histamine, and these materials belong to inflammatory mediator, the proof irritant laxative causes the enteric cavity hydrops and relieving constipation by stimulating intestinal to synthesize and discharge these inflammatory mediators just now, promptly by causing that enteritis produces discharge function, wherein:
(1), small intestinal irritant laxative: what belong to this type of medicine has Semen Ricini and Fructus Crotonis.This type of drug effect makes nuisance discharge rapidly in whole intestinal.The nutraceutical absorption of this class medicine meeting obstacle is not so fit into habitual constipation.Oleum Ricini is subjected to action of lipase to discharge castor oil acid in duodenum, Oleum Ricini and castor oil acid can both damage intestinal mucosa cells, cause inflammation, heavy dose of oral, can cause nausea, vomit, suffer from abdominal pain, pelvic cavity there is the reflexive hyperemization, after rushing down the short-term constipation can be arranged, therefore only use as intestinal cleaning agents.Fructus Crotonis is the most violent cathartic, and taking 20 can cause death, and generally only uses with the Semen Crotonis Pulveratum compatibility.
(2) large intestine irritant laxative: modern study finds that this type of medicine produces discharge function by causing the large intestine enteritis, and the toxic and side effects that causes stomachache, pelvic congestion, metrorrhagia and cause the large intestine canceration is arranged.Because its effect is rapidly, can not influence the absorption of nutrient at small intestinal, not enough to its toxic and side effects understanding in addition, to such an extent as to therefore all often be used to habitual constipation in the past today.But studies show that this class cathartic also has its toxic and side effects.
1), anthraquinone class: what belong to this type of medicine has Radix Et Rhizoma Rhei, Phamnus cathartica L., reed Cai, Folium Sennae, Semen Cassiae, Radix Polygoni Multiflori, an alizarin etc.After thinking that in the past this type of medicine enters colon, glycoside bond fission under bacterial action generates free derivant, stimulates myenteric nervous plexus reflexive ground to promote enterokinesia and cause defecation.Think that now the anthraquinone class causes that by inflammatory mediator enteritis produces discharge function, when clinical practice was found to take for a long time, colon X line morphology can show chronic ulcerative colitis.This type of drug overdose is taken and can be caused a series of toxic reactions of digestive tract, as nauseating, vomiting, tormina, heating, acute gastroenteritis, hemorrhagic gastritis, massive hemorrhage of gastrointestinal tract and pelvic organ hyperemia, can cause nephritis when serious, albuminuria, hematuria appear, take for a long time and can cause jaundice, hepatitis interstitialis chronica and large intestine pseudomelanosis, and can improve the danger of colorectal cancer morbidity.1095 patients are carried out splanchnoscopy, and the result shows long-term abuse anthracene class cathartic person, and its relative risk of suffering from colorectal carcinoma is 3.04 times of misuser not, and with the proof anthrol potential genotoxicity and carcinogenesis is arranged in rodent.In addition, the Radix Polygoni Multiflori excessive use, symptom to occur after mice poisons be instability of gait, tremble, turn-take, movement disorder, cyanosis, respiratory paralysis and death because anthraquinone class cathartic has more serious toxic and side effects, so should not be used for habitual constipation.
2) diphenols: what belong to this type of medicine has phenolphthalein class (phenolphthalein, second penta phenol liquor-saturated), phenol spit of fland class (phenol spit of fland, bisatin, triacephentinum, thiophenol spit of fland sodium) and a phenolic ester class (thiazine phenol spit of fland ester, pyrrole first bis-phenol ester, pyrrole first bis-phenol sulfur sodium).The diphenols model of action is similar to the anthraquinone class, mainly act on large intestine, modern study finds that this type of medicine is all by causing that enteritis produces discharge function, and with some other untoward reaction, as spasm even serious angina abdominis, stomachache, nausea and vomiting, tachycardia, idol anaphylaxis, dermatitis, drug eruption, mucosa injury are arranged, to the stimulation of kidney, life-time service can cause metabolic acid or alkali poisoning and protein losing enteropathy, and starts an inflammation of the liver and jaundice.This type of medicine is applicable to the constipation of asthenic type nerve.Spastic constipation, acute abdomen patient, anal fissure and hemorrhoid patients forbidding.In the diphenols medicine, pyrrole first bis-phenol ester (bisacodyl) side effect is lighter, can be used for the acute and chronic constipation, but milk or antacid must not be taken in 2 hours in the medication front and back, and the stomachache sense is arranged behind the small number of patients clothes, acute abdomen and anemia of pregnant woman's forbidding.
2, wettability cathartic: what belong to this type of medicine has glass amber monooctyl ester sodium, zinc butyl ester sodium sulfonate, a polyoxy second propylene.They are non-absorbent substantially surface active cpd, can make that water and fat are easy to mix and soften in the excrement, simultaneously the same with the irritant laxative intestinal that can stimulate is synthetic and discharge inflammatory mediator, therefore has the effect of infringement intestinal mucosa cells equally, and this detrimental effect has participated in rushing down the generation of effect down.Avoid and alizarin, the same usefulness of emollient laxative, absorb and intoxicating otherwise increase the latter.This type of medicine is applicable to the brachytherapy of the defecation of can not exerting oneself, and as the constipation of anus, rectum postoperative, bed, old man, poliomyelitis, myocardial infarction are to the chronic constipation nearly unavailable.
3, saline cathartic: what belong to this type of medicine has magnesium sulfate, sodium sulfate, sodium dihydrogen phosphate, a potassium hydrogen tartrate.Because it absorbs seldom, improve the osmotic pressure effect and play, make colonic volume gain, the expansion that produces because of liquid causes rushes down down, thinks that now promoting intestinal tissue to discharge histamine may also be one of mechanism of their raising intestinal permeabilitys.Wherein, magnesium sulfate is taken in a large number or the full person of kidney merit can cause poisoning and dehydration, and potassium hydrogen tartrate is used in a large number has infringement to kidney.This type of drug effect is rapid, just can prove effective with interior in general 6 hours.Owing to stimulate the intestinal wall effect strong, easily cause pelvic congestion, pregnancy period, menstrual phase, old person and enteritis, ileotyphus, peritonitis etc. are avoided usefulness.Generally only be used for intestinal tract cleaning and acute constipation.
4, emollient laxative: what belong to this type of medicine has liquid paraffin, Semen Armeniacae Amarum, a Semen Pruni.For using dilatancy cathartic person, this type of medicine commonly used.Liquid paraffin belongs to the mineral oils material, does not stimulate intestinal, is not absorbed, and lubrication is arranged, and can stop the enteral moisture absorption, and softening excrement piece makes it to be easy to pass through intestinal.But it disturbs the food normal stool to absorb, and with the absorption that can hinder fat-soluble A, D, E, K and calcium, phosphorus, idol can cause the osteomalacia for a long time.Take for a long time in intestinal and can form paraffinoma.In addition, can cause foreign body reaction in the lymphoid tissue, suction can cause lipid pneumonia.Because above disadvantage only can be used for accidental constipation and postoperative difficult defecation.Semen Armeniacae Amarum contains amygdalin 3%, produces hydrocyanic acid through enzyme hydrolysis, and toxicity is violent, the clothes 1mg/kg poisoning that can cause death, at first be nervous system,, eat amygdalin for a long time on a small quantity and can cause chronic poisoning because of the respiratory center and the vasomotor center of hydrocyanic acid infringement medulla oblongata itself.Semen Pruni contains amygdalin, the same Semen Armeniacae Amarum of toxicity.
5, osmotic laxative treatments
This class medicine comprises non-absorbent polyalcohols, as glycerol, mannitol, sorbitol, increases owing to the absorption that has hypertonicity to hinder moisture makes the enteric cavity internal volume, and intestinal wall is produced mechanical irritation, increases enterokinesia and causes relieving constipation.This type of medicine side effect is lighter.Glycerol can stimulate far-end colon and rectum and increase its osmotic pressure, can be used for acute constipation by chance, and oral glycerol generally has no adverse reaction, but excess ingestion can cause headache, thirsty, nausea and vomiting, and can influence the lipid metabolism of human body.Mannitol catharsis effect is strong, enter large intestine after, most of excrete with original shape, small part is produced gas by bacterial decomposition, so the enteral pneumatosis is more, patient often has abdominal distention stomachache or sense of discomfort, this type of medicine generally is used for acute constipation.
6, dilatancy cathartic
This class medicine is polysaccharide or the cellulose family that obtains from plant, and what belong to this type of medicine has Semen Plantaginis glue, agar, methylcellulose, a carboxymethyl cellulose.They are not destroyed by digestion in human body alimentary canal, experiment in vitro confirms that these materials can absorb moisture and expand into the lubricity gel, so they can make the moisture retention in vivo in enteric cavity, impel enterokinesia to increase because of volume gain, cause defecation with natural way.This class drug effect is mild, does not disturb the absorption of nutrient substance, nonsystemic reaction, but prolonged application, and be specially adapted to take food few slag food person and chronic constipation person, and diabetes, cardiovascular diseases, colorectal cancer, intestinal diverticulum etc. are had preventive effect.Recommend should take 20-25g dietary fiber every day at present in the world.Answer polydipsia water when this type of material is taken, block, in addition intestinal stenosis, intestinal resistance person forbidding otherwise can cause digestive tract.
In the research to constipation, do not introduce the notion of intestinal microecology as yet in the past.Recent study finds that bacillus bifidus and bacillus bifidus proliferant agent are effective to improving constipation, and late result is arranged.Reported in literature and we observe clinical patient and find that chronic constipation patient has the different dysbacteriosis of degree, show as the bacillus bifidus number and significantly reduce, and therefore can think that chronic constipation is accompanied by dysbacteriosis, or have the dysbacteriosis chronic constipation.Though both cause effect relations await further research, clinical observation is verified, and enteral microecological formulation is very effective to chronic constipation, and the improvement degree of its clinical symptoms and the hypertrophy quantity of bacillus bifidus have very strong positive correlation.Therefore should first-selected enteral microecological formulation for the dysbacteriosis chronic constipation.
The objective of the invention is to overcome the toxic and side effects of traditional cathartic, a kind of enteral microecological formulation of adjusting intestinal microbial population is provided, said preparation is adjusted function of intestinal canal by the hypertrophy that promotes bacillus bifidus in the intestinal, plays the effect of relieving constipation.
Oral formulations of the present invention prepares with following method:
Selected Radix Rehmanniae or Radix Rehmanniae dry tablet are raw material, and wherein the concocting method of Radix Rehmanniae dry tablet belongs to one of invention of the applicant, separate case application, and existing details are as follows with Radix Rehmanniae dry tablet concocting method, to guarantee the exploitativeness of technical solution of the present invention.
The concocting method of Radix Rehmanniae dry tablet:
Radix Rehmanniae is cut into the decoction pieces that thickness is the 2-5 millimeter, is placed on the drip pan and toasts, the thickness of decoction pieces on drip pan is the 5-10 millimeter, and baking temperature is between 30 ℃-95 ℃, and the drying room wet bulb temperature is between 15 ℃-38 ℃, and stoving time is 4-12 hour.
Loosening bowel to relieve constipation oral formulations preparation method of the present invention is as follows:
(1) extract: get the Radix Rehmanniae dry tablet, add water or 95% following ethanol water mixed liquid decoction extraction twice, preferably extract with the 0-30% ethanol water, add solvent 10-15 for the first time and doubly measure, add solvent 8-10 for the second time and doubly measure, merge extractive liquid, is standby.After perhaps squeezing the juice, add water or 95% following ethanol water mixing decoction extraction that 1-2.5 doubly measures, preferably extract with the 0-30% ethanol water with the bright Radix Rehmanniae.Extracting solution is standby.
(2) decolouring: the above-mentioned extracting solution that makes is reclaimed ethanol to the activated carbon that nothing alcohol flavor back adds (in dry product) 3-20% of medical material amount decolour.
(3) filtration, concentrated, fill: with destaining solution centrifugal filtration, centrifugal condition is 5000-20000 rev/min, centrifugation time is 5 minutes, reuse core (aperture 10-20 μ), decompress filter, micro-pore-film filtration then, aperture 0.15 μ, micro-filtrate is evaporated to density 1.05-1.30 (25 ℃), put 0-5 ℃ of cold preservation 24-72 hour, get supernatant.
Above-mentioned extracting solution can be made into the oral formulations of different dosage form, and the supernatant after the cold preservation is measured stachyose and catalpol content, is adjusted to debita spissitudo, making content of stachyose is 350mg/ml, catalpol 13mg/ml, density 1.10-1.25, pH value 5.0-6.5 makes the loosening bowel to relieve constipation oral liquid.Be the brownish red transparency liquid, the little flavor of sweet in the mouth.
With above-mentioned supernatant thin up, make little threose content 35mg/ml, catalpol content 1.3mg/ml, density 1.05-1.07, pH value 5.0-6.0 makes the beverage type oral liquid.
With above-mentioned supernatant lyophilization, make light yellow loose lyophilization powder, it is sweet to distinguish the flavor of, little hardship.
Medicine of the present invention is better than traditional relieving constipation medicine at aspects such as relieving constipations:
(1) mechanism of action: adjust function of intestinal canal, promote the activity of physiological defecation.Relieving constipation drug mechanism in the past is different, but total all intestinal produced momentary stimulation and work.Wherein, commonly used irritant laxative, wettability cathartic, saline cathartic, particularly anthraquinone class, diphenols cathartic all is by stimulating intestinal synthetic and discharge inflammatory mediator and produce the enteric cavity hydrops, promptly by stimulating enteritis to play defecating feces excretion.This medicine is taken a series of untoward reaction such as can causing chronic ulcerative colitis for a long time.The oral preparation capable of enriching yin and moistening intestines mechanism of action of the present invention is then fully different, and its relieving constipation mechanism (1. is that the suction moisture retention of the indigestibility composition stachyose etc. by wherein and the laxative action of catalpol composition are realized.2. be by the stachyose composition to bacillus bifidus hypertrophy in the intestinal, regulate intestinal microbial population and realize.Therefore we can say that the YIN nourishing intestine-moisturizing oral liquid plays defecating feces excretion by adjusting function of intestinal canal.Its effect very relaxes, and freely and not rushes down, and is seemingly moving phase with the physiological defecation, for meeting most the relieving constipation medicine of Human Physiology needs.
(2) focus on adjustment, have late result.Relieving constipation medicine in the past is property defecating feces excretion for once generally, can only solve the symptom of constipation, cures the symptoms, not the disease no late result.Oral preparation capable of enriching yin and moistening intestines of the present invention is adjusted intestinal microecology, recovers the intestinal normal function, so its relieving constipation treating both the principal and secondary aspects of a disease, not only solves symptom for the moment, and has late result.
(3) its functions of loosening bowel relieving constipation is extensive, to asthenia of qi and blood, deficiency of both QI and YIN, deficiency of both the splenic and pulmonary QI deficiency, gastrointestinal intrinsic heat, the moon of Chinese medical discrimination hinder that intestinal is withered, the deficiency of vital energy and the unable various constipation of large intestine conduction all have good effect, especially constipation of deficiency of YIN intestinal dryness type chronic habitual and chronic senile constipation are the most effective.
(4) safety non-toxic can relievedly be taken for a long time.
Other relieving constipation medicine has various toxicity and untoward reaction in various degree more at present.Oral preparation capable of enriching yin and moistening intestines of the present invention, the medical material of selecting for use are not seen the toxic reaction report through the test of more than one thousand years tradition medication, and be modern to its composition Study, do not see toxic component.Do not add any antiseptic, coloring agent, correctives in the preparation process, through animal acute toxicity, long term toxicity test and the clinical observation of strictness, do not find any toxic reaction again, the patient can relievedly take to the greatest extent for a long time.
(5) hypertrophy bacillus bifidus has multiple medical care effect.
Bacillus bifidus is important probiotics in the intestinal, and its many-sided medical care effect is generally acknowledged, the oral preparation capable of enriching yin and moistening intestines relieving constipation while of the present invention, and the hypertrophy bacillus bifidus, the multiple disease that causes reducing with divergent bacillus has prevention, treatment or improvement effect.
(6) be better than the soybean oligo saccharide that Japan develops.
The soybean oligo saccharide of Japan's exploitation is comparatively ideal intestinal microecology regulator, can be used for treating constipation, but be grouped into, remain in some shortcomings from its one-tenth, its effective ingredient soybean oligo saccharide (stachyose stdchyose, Raffinose raffinose) content is lower, only accounts for 30%, and contains in a large number and can absorb sugar, 44% sucrose and 23% monosaccharide, this is to the diabetes patient, and overweight people, old people are uncomfortable.After the lyophilization of YIN nourishing intestine-moisturizing oral liquid, measure its each component content, stachyose is more than 65%, Raffinose 2%, and sucrose 1.85%, fructose 2.50%, catalpol 2.94%, the sugared content that absorbs wherein is extremely low, and active constituent content is very high.This is much better than the soybean oligo saccharide of Japan.
(7) be better than the relieving constipation preparation that is used as medicine with Radix Rehmanniae, Radix Rehmanniae Preparata.
Radix Rehmanniae according to the concocting method difference, is divided into aquatic foods, dried, Radix Rehmanniae Preparata at the medicinal history in existing two over thousands of years of China, and function respectively has difference.Wherein, Radix Rehmanniae, Radix Rehmanniae have the cloudy function of hindering constipation of treatment.As " Zengye Tang ", be used for constipation with heat retention.The relieving constipation medicine that contains Radix Rehmanniae in the market, or become compound recipe to use with the other drug compatibility, perhaps use Radix Rehmanniae, Radix Rehmanniae Preparata.Do not see the Radix Rehmanniae single is used in constipation, more do not see with Radix Rehmanniae or Radix Rehmanniae dry tablet to be that raw material is made medicament and is used in constipation.
The process of preparing Chinese medicine to Radix Rehmanniae is discovered, stachyose in the Radix Rehmanniae, catalpol are along with concocting into Radix Rehmanniae, Radix Rehmanniae Preparata and reduce.Stachyose is from more than 40% of bright ground, reduce to 20% of Radix Rehmanniae, the 5-8% of Radix Rehmanniae Preparata, catalpol is reduced to 1% of Radix Rehmanniae from Radix Rehmanniae more than 5%, 0.1% of Radix Rehmanniae Preparata, and absorbable monosaccharide, disaccharidase content improve greatly in the processed product Radix Rehmanniae, Radix Rehmanniae Preparata.By as seen above-mentioned, with the relieving constipation is purpose, use Radix Rehmanniae, Radix Rehmanniae Preparata is used as medicine as raw medicinal material is not very reasonable, being to have relieving constipation on the one hand is purpose, use Radix Rehmanniae, Radix Rehmanniae Preparata is used as medicine as raw medicinal material is not very reasonable, be that the effective component content with relieving constipation and bacillus bifidus proliferative effect reduces greatly on the one hand, be to absorb sugared content on the other hand and increase greatly, and diabetes patient, overweight people, old people should not be taken.Therefore oral formulations of the present invention is better than containing Radix Rehmanniae on the relieving constipation effect, the preparation of Radix Rehmanniae Preparata, and avoided dried ground, Radix Rehmanniae Preparata can absorb the too much adverse effect of sugar.
Medicine of the present invention has been carried out the test of defecation frequency, and the test of intestinal contents fltting speed is to the influence of dehydration constipation model intestinal contents fltting speed and defecation frequency, to the influence of the different intestinal segment moisture absorption of mice, to the influence of the intestinal that exsomatizes.Experimental result shows that the YIN nourishing intestine-moisturizing oral liquid causes the animal of constipation that the very significantly effect of loosening bowel to relieve constipation is all arranged to intact animal and dehydration, mechanism of action is that first it can obviously suppress the absorption of large intestine to moisture, make large intestine enteric cavity internal volume increase and cause defecation, second lactic acid, the acetic acid owing to stachyose metabolism generation under the bacillus bifidus effect can promote that enterokinesia causes defecation.
4 tame hospitalize 118 routine chronic constipation patients' the observation through Beijing, its result shows that medicine subject range of the present invention is extensive, to all asthenia of qi and bloods, deficiency of both QI and YIN, deficiency of both the splenic and pulmonary QI deficiency, gastrointestinal intrinsic heat, the moon hinder that intestinal is withered, the deficiency of vital energy and the unable various constipation of large intestine conduction, curative effect is preferably all arranged, wherein, for cloudy blood deficiency of body fluid, intestinal lose in make moist, the deficiency of YIN and to give birth to the interior-heat person particularly suitable.Treatment constipation total effective rate reaches 91.5%, total obvious effective rate (clinical cure rate adds obvious effective rate) 75.42%, and do not see toxic and side effects.
Embodiment 1
Get 10 kilograms of Radix Rehmanniae (being equivalent to 2 kilograms of Radix Rehmanniae dry tablets), behind the squeezing extracting juice, 3 elutions of 25 kilograms of moisture of reuse, with the eluant heated and boiled, add activated carbon 60 grams (3%), heated and boiled decolouring, 20000 rev/mins, centrifugal filtration 5 minutes, sand filtration, core aperture (10 μ) micro-pore-film filtration, aperture 0.15 μ, the fill sterilization makes the dilution type intestine-moisturizing oral liquid.
Embodiment 2
With 10 kilograms of Radix Rehmanniae dry tablets, add 200 kilograms in water, divide to boil for 2 times and carry, leach cooking liquid adds 8% decolorizing with activated carbon, centrifugal filtration, sand filtration, micro-pore-film filtration, aperture 0.15 μ is evaporated to proportion 1.30, concentrated solution is put 0-5 ℃ of cold preservation 24 hours, get supernatant, adjust concentration, make density reach 1.10-1.25, embedding, sterilization makes the YIN nourishing intestine-moisturizing oral liquid.
Embodiment 3
With 10 kilograms of Radix Rehmanniae dry tablets, be ground into fine particle, cross 100 mesh sieves, with 50% ethanol extraction 4 times, 400 kilograms of shared solvents, being recycled to does not have the alcohol flavor, adjust volume, add 1.5 kilograms of decolorizing with activated carbon, sand filtration, be evaporated to proportion 1.30, supernatant is got in cold preservation 48 hours, adjust concentration, making density is 1.10-1.25, embedding, sterilization makes oral liquid.