阅读说明：本技术 一种清洁肠道的肠道准备药物组合物及其制备方法 (Intestinal tract preparation pharmaceutical composition for cleaning intestinal tract and preparation method thereof ) 是由 叶梓 林卫军 石国良 洪诗群 蔡许斌 王羽娟 于 2020-04-16 设计创作，主要内容包括：本发明公开了一种清洁肠道的肠道准备药物组合物及其制备方法,所述肠道准备药物组合物按重量份数比包括以下组分：65-99份的L-阿拉伯糖和1-15份的木糖醇；所述L-阿拉伯糖的纯度≥99％；所述木糖醇的纯度≥99％；所述肠道准备药物组合物制成片剂、胶囊剂、口服液、颗粒剂、散剂或糖浆剂；自有筛选的特异性热带假丝酵母,能够选择性将木糖转化为木糖醇,酵母还能利用原料中除了L-阿拉伯糖之外的杂质,特别是在色谱出峰时间和L-阿拉伯糖出峰重叠的杂质,以杂质作为营养成分,可以实现与L-阿拉伯糖高效分离,达到一个物料同时获取木糖醇和L-阿拉伯糖两大产品的效果,具有生产成本优势。(The invention discloses an intestinal tract preparation pharmaceutical composition for cleaning intestinal tracts and a preparation method thereof, wherein the intestinal tract preparation pharmaceutical composition comprises the following components in parts by weight: 65-99 parts of L-arabinose and 1-15 parts of xylitol; the purity of the L-arabinose is more than or equal to 99 percent; the purity of the xylitol is more than or equal to 99 percent; the intestinal tract preparation pharmaceutical composition is prepared into tablets, capsules, oral liquid, granules, powder or syrup; the screened specific candida tropicalis can selectively convert xylose into xylitol, and the yeast can utilize impurities in raw materials except L-arabinose, particularly impurities overlapping with the peak time of the chromatogram and the peak of the L-arabinose, and can realize high-efficiency separation from the L-arabinose by taking the impurities as nutritional ingredients, so that the effect of simultaneously obtaining two products of xylitol and L-arabinose by one material is achieved, and the yeast has the advantage of production cost.)

1. The intestinal tract preparation pharmaceutical composition for cleaning the intestinal tract is characterized by comprising the following components in parts by weight: 65-99 parts of L-arabinose and 1-15 parts of xylitol.

2. The enteral preparation pharmaceutical composition for cleansing the intestinal tract of claim 1, wherein: the purity of the L-arabinose is more than or equal to 99 percent; the purity of the xylitol is more than or equal to 99 percent.

3. The enteric-coated, bowel-preparing pharmaceutical composition according to claim 1, wherein the enteric-coated, bowel-preparing pharmaceutical composition comprises the following components in parts by weight: 95 parts of L-arabinose and 5 parts of xylitol.

4. The enteral preparation pharmaceutical composition for cleansing the intestinal tract of claim 1, wherein: the composition for preparing the intestinal tract can be prepared into tablets, capsules, oral liquid, granules, powder or syrup.

5. A process for the preparation of a pharmaceutical composition for enteral preparation according to any one of claims 1 to 4, comprising the steps of:

s1, obtaining a raw material mother liquor containing xylose and L-arabinose, diluting and decolorizing the raw material mother liquor, inoculating specific yeast, fermenting by using the specific yeast, converting xylose into xylitol, and removing impurities affecting the purity of the L-arabinose; the raw material mother liquor is derived from plant extracts of lignocellulose;

s2, after the fermentation is finished, thalli are recovered through centrifugation, and L-arabinose sugar solution and xylitol solution are respectively obtained after the fermentation liquor is subjected to ion exchange, vacuum concentration and chromatographic separation;

s3, concentrating the separated and purified L-arabinose sugar solution in vacuum until the solid content is 55-65%, obtaining L-arabinose crystals in a continuous flow sugar boiling crystallization mode, and centrifuging at high speed to remove mother liquor to obtain powdery crystals of L-arabinose;

s4, vacuum concentrating the xylitol solution obtained after separation and purification until the solid content is 88% -92%, obtaining xylitol crystals by means of continuous cooling crystallization, and obtaining powdery crystal xylitol by high-speed centrifugation and throwing away mother liquor;

s5, drying and sieving the powdery L-arabinose and xylitol to respectively obtain finished L-arabinose and xylitol powders, and mixing the finished L-arabinose and xylitol powders according to a proportion to obtain the intestinal tract preparation pharmaceutical composition.

6. A process for preparing a pharmaceutical composition for enteral preparation according to claim 5, wherein: the specific yeast is candida tropicalis.

7. The method for preparing the intestinal tract preparation pharmaceutical composition according to claim 6, wherein the dilution method of the raw material mother liquor in the step S1 is specifically as follows: adding pure water into the raw material mother liquor with the solid content of more than or equal to 50 percent until the raw material mother liquor is diluted to the solid content of 25 to 35 percent.

8. The method for preparing the intestinal tract preparation pharmaceutical composition according to claim 7, wherein the method for removing the color of the raw material mother liquor in step S1 comprises: diluting the raw material mother liquor, heating to 60-65 deg.C, adding activated carbon to adsorb pigment, filtering with plate frame to remove activated carbon, collecting the clear liquid, and adding into fermentation tank.

9. The method for preparing a pharmaceutical composition for enteral preparation according to claim 8, wherein the specific yeast fermentation process in step S1 is specifically as follows: inoculating the specific yeast into the filtered clear liquid, wherein the inoculation amount is 5-20 wt%, starting a stirrer to uniformly mix the specific yeast and the clear liquid, controlling the temperature at 30-33 ℃, maintaining the pressure in the tank at 0.005-0.01MPa, ventilating, stirring, culturing, and discharging after continuous fermentation is adopted for 40-55 h.

10. A process for preparing a pharmaceutical composition for enteral preparation according to claim 5, wherein: the raw material mother liquor is plant extract from corncob, corn bran, straw, bean skin, bean dregs, sugarcane leaf or bagasse.

Technical Field

The invention relates to the field of biomedicine, in particular to an intestinal tract preparation pharmaceutical composition for cleaning intestinal tracts and a preparation method thereof.

Background

Colonoscopy is the most effective method for diagnosing and treating colonic diseases. The quality of intestinal tract preparation directly influences the diagnosis and treatment effect of colonoscopy, and insufficient intestinal tract preparation not only increases the operation time of colonoscopy and influences the image quality and treatment effect, but also can cause serious conditions such as intestinal tract injury and the like. Effective intestinal tract preparation is the key for successful colonoscopy, and clean intestinal tracts provide guarantee for inserting a scope, observing, diagnosing and even performing surgical treatment, and can also reduce the psychological pressure and burden of patients.

The intestinal tract preparation methods are different, the effects are different, and the selection of the intestinal tract preparation method with good intestinal tract clearing effect, small side effect and wide application range is very important. Oral osmotic, irritant and volume cathartic drugs such as magnesium sulfate, sodium sulfate, compound polyethylene glycol electrolyte powder, polyethylene glycol tablet, etc. are common drugs for intestinal tract preparation at present.

The application of chemical medicines in intestinal tract cleaning agents has been reported, and commonly used intestinal tract cleaning medicines are mainly a compound containing polyethylene glycol and salts, for example, Chinese patent CN101897721A discloses an enema composition for preparing endoscopy, especially colonoscopy, and the composition mainly contains polyethylene glycol, ascorbic acid or salts thereof, alkali metal or sulfate thereof, electrolytes such as sodium chloride and potassium chloride, and finally contains flavoring agents, so that effective intestinal tract cleaning can be achieved. Chinese patent CN1850112A discloses a polyethylene glycol-electrolyte oral solution, which is composed of polyethylene glycol, sodium chloride, potassium chloride, sodium bicarbonate, sodium sulfate, edetate, sweetener and edible essence, and has the characteristics of quick response, safety, reliability and good cleaning effect. Most of the intestinal tract cleaning agents or medicines are chemical preparations, and the laxatives are often poor in taste, need to be supplemented with sweeteners to adjust the taste, are large in dosage, are prone to adverse reaction symptoms such as nausea, vomiting and abdominal distension, have an unsatisfactory intestinal tract cleaning effect, cannot achieve the effect of enteroscopy observation, cause a patient to repeat an intestinal tract preparation process, not only affect the psychology of intestinal tract preparation before enteroscopy detection of the patient, but also increase the medical burden of enteroscopy.

The application of saccharides in an intestinal tract cleaning agent is also reported in a small amount, and Chinese patent CN102512430A discloses an intestinal tract cleaning pharmaceutical composition, which relates to an intestinal tract cleaning pharmaceutical composition containing L-glucose and L-mannose. Chinese patent CN104434936A discloses L-glucose colon cleansing agents and their use, mainly L-glucose monohydrate and compositions thereof, finding that L-glucose oral solutions can overcome the caking during the dissolution of anhydrous L-glucose, can be administered more accurately and further improve colon cleansing and laxative properties. Both of the above-mentioned patents relate to L-glucose or a composition thereof as an intestinal tract cleanser, and have a disadvantage in that L-glucose or a composition thereof is a product which requires further processing, particularly L-glucose and L-mannose are obtained by chemically reacting L-arabinose as a raw material, and thus the problem of safety of by-products cannot be avoided.

Disclosure of Invention

The invention aims to provide an intestinal tract preparation pharmaceutical composition for cleaning intestinal tracts and a preparation method thereof, which can solve the problems of poor taste and unstable intestinal tract cleaning effect of the existing intestinal tract cleaning drugs and can effectively reduce adverse reactions in the intestinal tract cleaning process.

In order to achieve the purpose, the invention adopts the following technical scheme:

an intestinal tract preparation pharmaceutical composition for cleaning intestinal tracts comprises the following components in parts by weight: 65-99 parts of L-arabinose and 1-15 parts of xylitol.

Preferably, the purity of the L-arabinose is more than or equal to 99 percent; the purity of the xylitol is more than or equal to 99 percent.

Preferably, the intestinal tract preparation pharmaceutical composition comprises the following components in parts by weight: 95 parts of L-arabinose and 5 parts of xylitol.

Preferably, the intestinal tract preparation pharmaceutical composition is prepared into tablets, capsules, oral liquids, granules, powders or syrups.

A method of preparing a bowel preparation pharmaceutical composition comprising the steps of:

s1, obtaining a raw material mother liquor containing xylose and L-arabinose, diluting and decolorizing the raw material mother liquor, inoculating specific yeast, fermenting by using the specific yeast, converting xylose into xylitol, and removing impurities affecting the purity of the L-arabinose; the raw material mother liquor is derived from plant extracts of lignocellulose;

s2, after the fermentation is finished, thalli are recovered through centrifugation, and L-arabinose sugar solution and xylitol solution are respectively obtained after the fermentation liquor is subjected to ion exchange, vacuum concentration and chromatographic separation;

s3, concentrating the separated and purified L-arabinose sugar solution in vacuum until the solid content is 55-65%, obtaining L-arabinose crystals in a continuous flow sugar boiling crystallization mode, and centrifuging at high speed to remove mother liquor to obtain powdery crystals of L-arabinose;

s4, vacuum concentrating the xylitol solution obtained after separation and purification until the solid content is 88% -92%, obtaining xylitol crystals by means of continuous cooling crystallization, and obtaining powdery crystal xylitol by high-speed centrifugation and throwing away mother liquor;

s5, drying and sieving the powdery L-arabinose and xylitol to respectively obtain finished L-arabinose and xylitol powders, and mixing the finished L-arabinose and xylitol powders according to a proportion to obtain the intestinal tract preparation pharmaceutical composition.

Preferably, the specific yeast is candida tropicalis.

Preferably, the method for diluting the raw material mother liquor in step S1 specifically comprises: adding pure water into the raw material mother liquor with the solid content of more than or equal to 50 percent until the raw material mother liquor is diluted to the solid content of 25 to 35 percent.

Preferably, the method for removing color of the raw material mother liquor in step S1 specifically comprises: diluting the raw material mother liquor, heating to 60-65 deg.C, adding activated carbon to adsorb pigment, filtering with plate frame to remove activated carbon, collecting the clear liquid, and adding into fermentation tank.

Preferably, the specific yeast fermentation process in step S1 is specifically: inoculating the specific yeast into the filtered clear liquid, wherein the inoculation amount is 5-20 wt%, starting a stirrer to uniformly mix the specific yeast and the clear liquid, controlling the temperature at 30-33 ℃, maintaining the pressure in the tank at 0.005-0.01MPa, ventilating, stirring, culturing, and discharging after continuous fermentation is adopted for 40-55 h.

Preferably, the raw material mother liquor is a plant extract derived from corncobs, cornhusks, bran, straw, soybean hulls, soybean dregs, sugarcane leaves or bagasse.

After the technical scheme is adopted, compared with the background technology, the invention has the following beneficial effects:

1. the L-arabinose adopted by the invention is not easy to be absorbed by human body, and the excretion reaction can be generated after a certain dosage of L-arabinose is taken orally, because the L-arabinose is not easy to be digested and absorbed by digestive enzyme of human body, and forms a thick sugar water environment after entering the large intestine, water around the intestine can be absorbed and enters the intestinal tract, and under the action of osmotic pressure difference and the characteristics of intestinal semipermeable membrane, the water enters the intestine from the outside of the intestinal tract, so that the stubborn stool is softened, the stool is produced, the intestinal contents are discharged, the effect of cleaning the intestinal tract is achieved, and the whole process is a physical process without generating side effect.

2. The xylitol adopted by the invention is an intermediate of carbohydrate metabolism of a human body, under the condition that the carbohydrate metabolism is influenced by the lack of insulin in the body, the xylitol does not need to be promoted by insulin, can permeate cell membranes, is absorbed and utilized by tissues, promotes the synthesis of hepatic glycogen, provides nutrition and energy for cells, does not cause the rise of blood sugar value, eliminates the symptoms of polyphagia, polydipsia and polyuria of a diabetic patient after taking the xylitol, is very suitable for the diabetic patient to eat, and can be utilized by microorganisms in an intestinal tract to generate short-chain fatty acids beneficial to the body, and the fatty acids can stimulate the enteric nerve and enhance the intestinal tract peristalsis.

3. The L-arabinose is not absorbed by human body, and is easy to accumulate on the intestinal wall in the intestinal tract in cooperation with xylitol, a hypertonic environment is formed in the intestinal tract, the water content of the intestinal cavity is improved, the neural activity of the intestinal wall can be enhanced, the intestinal tract power is activated, and the intestinal tract peristalsis is promoted, so that the intestinal tract contents are discharged out of the body, and a more effective intestinal tract cleaning effect can be achieved.

4. The yeast used in the invention is the screened specific candida tropicalis, can selectively convert xylose into xylitol, and can avoid the safety problem that a catalyst needs to be added in chemical hydrogenation; the yeast can also utilize impurities in the raw materials except the L-arabinose, particularly the impurities overlapping with the chromatographic peak-out time and the L-arabinose peak-out time, and the impurities are used as nutrient components, thereby achieving the purposes of removing the impurities and improving the purity of the L-arabinose; meanwhile, the specific candida tropicalis can also convert xylose in the raw material into xylitol, can realize high-efficiency separation from the L-arabinose, achieves the effect of simultaneously obtaining two products of xylitol and L-arabinose from one material, and has the advantage of production cost.

5. The L-arabinose and xylitol composition can be used for preparing a medicament for a colon endoscope examination intestinal tract, and has the following advantages for a colon endoscope examination intestinal tract preparer: the medicine is convenient to carry and simple in administration mode; the composition belongs to functional sugar alcohol, other components are not required to be added, particularly xylitol is added, the taste is fresh and sweet, and the mouthfeel is greatly improved; synergistically enhance intestinal osmotic pressure, promote peristalsis more obviously, be more favorable for discharging contents, have better effect of clearing intestines and have no adverse reaction and side effect.

Drawings

FIG. 1 is an L-arabinose purity HPLC calcium column map in example 3 of the present invention;

FIG. 2 is a HPLC calcium column spectrum of xylitol purity in example 3 of the present invention.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

In the invention, all parts and percentages are weight units, and all equipment, raw materials and the like can be purchased from the market or are commonly used in the industry, if not specified. The methods in the following examples are conventional in the art unless otherwise specified.

An intestinal tract preparation pharmaceutical composition for cleaning intestinal tracts comprises the following components in parts by weight: 65-99 parts of L-arabinose and 1-15 parts of xylitol.

The purity of the L-arabinose is more than or equal to 99 percent; the purity of the xylitol is more than or equal to 99 percent.

The intestinal tract preparation pharmaceutical composition comprises the following components in parts by weight: 95 parts of L-arabinose and 5 parts of xylitol.

The composition for preparing the intestinal tract can be prepared into tablets, capsules, oral liquid, granules, powder or syrup.

A method of preparing a bowel preparation pharmaceutical composition comprising the steps of:

s1, obtaining a raw material mother liquor containing xylose and L-arabinose, diluting and decolorizing the raw material mother liquor, inoculating specific yeast, fermenting by using the specific yeast, converting xylose into xylitol, and removing impurities affecting the purity of the L-arabinose; the raw material mother liquor is derived from plant extracts of lignocellulose; the raw material mother liquor used by the invention is purchased from Haining waves Biotechnology Co., Ltd;

s2, after the fermentation is finished, thalli are recovered through centrifugation, and L-arabinose sugar solution and xylitol solution are respectively obtained after the fermentation liquor is subjected to ion exchange, vacuum concentration and chromatographic separation;

s3, concentrating the separated and purified L-arabinose sugar solution in vacuum until the solid content is 55-65%, obtaining L-arabinose crystals in a continuous flow sugar boiling crystallization mode, and centrifuging at high speed to remove mother liquor to obtain powdery crystals of L-arabinose;

s4, vacuum concentrating the xylitol solution obtained after separation and purification until the solid content is 88% -92%, obtaining xylitol crystals by means of continuous cooling crystallization, and obtaining powdery crystal xylitol by high-speed centrifugation and throwing away mother liquor;

s5, drying and sieving the powdery L-arabinose and xylitol to respectively obtain finished L-arabinose and xylitol powders, and mixing the finished L-arabinose and xylitol powders according to a proportion to obtain the intestinal tract preparation pharmaceutical composition.

The specific yeast is candida tropicalis.

The method for diluting the raw material mother liquor in the step S1 specifically comprises the following steps: adding pure water into the raw material mother liquor with the solid content of more than or equal to 50 percent until the raw material mother liquor is diluted to the solid content of 25 to 35 percent.

The color removing method of the raw material mother liquor in the step S1 specifically comprises the following steps: diluting the raw material mother liquor, heating to 60-65 deg.C, adding activated carbon to adsorb pigment, filtering with plate frame to remove activated carbon, collecting the clear liquid, and adding into fermentation tank.

The specific yeast fermentation process in the step S1 specifically comprises the following steps: inoculating the specific yeast into the filtered clear liquid, wherein the inoculation amount is 5-20 wt%, starting a stirrer to uniformly mix the specific yeast and the clear liquid, controlling the temperature at 30-33 ℃, maintaining the pressure in the tank at 0.005-0.01MPa, ventilating, stirring, culturing, and discharging after continuous fermentation is adopted for 40-55 h.

The raw material mother liquor is plant extract from corncob, corn bran, straw, bean skin, bean dregs, sugarcane leaf or bagasse.