CN108354957B - Application of kalimeris indica or kalimeris indica extract in preparation of medicine for treating non-infectious inflammation and medicine - Google Patents

Abstract

The invention provides an application of herba Kalimeridis or herba Kalimeridis extract in preparing a medicament for treating non-infectious inflammation, and the herba Kalimeridis can effectively solve the problems of long treatment period, poor curative effect and low tolerance of patients in the current stage of non-infectious enteritis. The invention also provides a medicament for treating non-infectious inflammation, which can greatly shorten the treatment period of the non-infectious inflammation and quickly repair the inflammatory wound of a patient.

Description

Application of kalimeris indica or kalimeris indica extract in preparation of medicine for treating non-infectious inflammation and medicine

Technical Field

The invention relates to the field of medicines, in particular to an application of kalimeris indica or kalimeris indica extract in preparing a medicine for treating non-infectious inflammation and a medicine.

Background

Inflammation, a very common and important basic pathological process, is a defense response of the body to stimuli. Generally, antibiotic drugs are mainly used for treating infectious diseases caused by microbial infection such as bacteria, and the treatment effect is remarkable. However, some non-infectious inflammations, i.e. physical inflammations, have a long course and are highly harmful to the patient. There is currently no good treatment for such infections, and radiation enteritis is exemplified below.

With the progress of radiotherapy technology, radiotherapy has become an important method for the comprehensive treatment of many malignant tumors. Over thirty-one million people worldwide receive pelvic radiation therapy each year, with about 80% of patients experiencing acute diarrhea during or after radiation therapy, severely affecting the patient's rate of completion of radiation therapy. About 10-21% of patients who receive pelvic radiotherapy suffer from radiation enteritis, which can affect small intestine, colon and rectum and is manifested by abdominal pain, diarrhea, mucus, bloody stool, etc. The radiation enteritis has long course of disease, can be prolonged to years or even decades after radiotherapy, causes great pain to the daily life of patients, and even threatens the life safety of the patients.

At present, no clear standard treatment scheme exists for radiation enteritis, and symptomatic support treatment is mainly used clinically. The treatment means of western medicine mainly comprises nutrition support, hyperbaric oxygen treatment and the like. Although parenteral nutritional support can provide necessary energy and nutrition for patients and protect the damaged intestinal mucosa from stimulation of food and digestive juice, it is beneficial to intestinal repair; however, long-term fasting causes atrophy of intestinal mucosa and increased intestinal wall permeability, and also causes more complications such as impaired liver function, intestinal bacterial translocation and the like. Hyperbaric oxygen treatment, which stimulates angiogenesis in the local radiation injury area, increases oxygen supply to the injury area, and promotes repair of the injured intestinal tract. Hyperbaric oxygen treatment is relatively safe, common side effects are ear barotrauma, anxiety and temporary myopia, but the treatment period of the method is long, about 6-8 weeks, the cost is high, and a professional treatment mechanism is needed.

The basic idea of traditional Chinese medicine treatment of radiation enteritis is to strengthen body resistance and eliminate pathogenic factors, clear heat and remove toxicity, stop bleeding and cool blood. The commonly used medicines comprise bitter cold and dampness-drying medicines such as coptis chinensis, phellodendron, scutellaria baicalensis and the like, kidney-warming and spleen-tonifying medicines such as astragalus mongholicus, codonopsis pilosula, bighead atractylodes rhizome, angelica sinensis, white paeony root, cinnamon, nutmeg, elecampane, myrobalan, lotus seed and the like, yin-nourishing and qi-tonifying medicines such as ginseng, radix ophiopogonis, fructus cannabis and the like, liver-soothing and dampness-removing medicines such as radix bupleuri, albizia julibrissin, radix sileris, poria cocos and the like, qi-promoting, blood-activating, heat-clearing and stasis-removing medicines such as pollen typhae, trogopterus dung, radix paeoniae rubra, radix achyranthis. For bloody stool, hemostatic herbs such as san Qi and sanguisorba root are often added. However, these drugs are often administered in a compound way, and the patients take more drugs at one time, which increases the burden of intestinal metabolism and the stimulation to intestinal mucosa, and the treatment effect is poor.

The administration route for treating radiation enteritis, whether Western medicine or Chinese medicine, is commonly enema, or oral administration, or the combination of enema and oral administration, or rectal instillation, or rectal suppository and the like. Although the drug can directly reach the injured part by the administration in the intestinal tract, the drug concentration of the intestinal tract, especially intestinal mucosa cells, is higher than that of the blood plasma, and the first-pass effect of the drug is avoided; patients are poorly tolerated by these modes of administration. Because most radiation enteritis has symptoms of diarrhea and frequent defecation, especially acute radiation enteritis, a lot of patients need to defecate 20-30 times per day, even have fecal incontinence, and rectal or colonic administration is not only difficult to retain medicines, but is more likely to stimulate defecation.

Disclosure of Invention

The invention aims to provide the application of the kalimeris indica or the kalimeris indica extract in preparing the medicine for treating the non-infectious inflammation, so as to solve the problems of long treatment period, poor curative effect and low tolerance of patients in the current stage of non-infectious enteritis.

The second purpose of the invention is to provide a medicine for treating non-infectious inflammation, which can greatly shorten the treatment period of non-infectious inflammation and quickly repair the inflammatory wound of a patient.

In order to achieve the above purpose of the present invention, the following technical solutions are adopted:

use of herba Kalimeridis in preparing medicine for treating non-infectious inflammation is provided.

Use of Kalimeris indica extract in preparing medicine for treating non-infectious inflammation is provided.

A medicine for treating non-infectious inflammation comprises herba Kalimeridis extract and pharmaceutically acceptable carrier or adjuvant.

Compared with the prior art, the invention has the beneficial effects that:

the novel application of the kalimeris indica or the kalimeris indica extract in preparing the medicine for treating the non-infectious inflammation and the medicine can greatly shorten the treatment period of the non-infectious inflammation and enable the inflammatory wound of a patient to be quickly repaired. Meanwhile, the tolerance of the patient can be improved, the physiological pain of the patient is relieved, and the psychological panic of the patient is eliminated, so that the problems of long treatment period, poor curative effect and low tolerance of the patient of the non-infectious inflammation at the present stage are effectively solved.

Detailed Description

Embodiments of the present invention will be described in detail below with reference to examples, but it will be understood by those skilled in the art that the following examples are only illustrative of the present invention and should not be construed as limiting the scope of the present invention. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.

The present embodiment provides the use of kalimeris indica or kalimeris indica extract for the manufacture of a medicament for the treatment of non-infectious inflammation.

Herba Kalimeridis (L.) Sch.Bip of Compositae is a whole herb of Kalimerisinica (L.) of Kalimeriisindica, herba Kalimeridis, and has effects of clearing heat and detoxicating, cooling blood and stopping bleeding, removing blood stasis and detumescence, resolving food stagnation and promoting diuresis, dispelling pathogenic wind and calming liver, and can be used for treating hematemesis, epistaxis, bloody dysentery, metrorrhagia, traumatic hemorrhage, jaundice, edema, stranguria with turbid urine, common cold, cough, sore throat, hemorrhoid, carbuncle swelling, erysipelas, infantile malnutrition, etc., with good therapeutic effect on many symptoms. Meanwhile, kalimeris indica is not found to have toxicity no matter the classic traditional Chinese medicine and the modern pharmacological and toxicological research. Therefore, the kalimeris indica can be used for developing therapeutic drugs, and the patent drug prospect is good.

The inventor finds that the kalimeris indica extract can effectively treat lung infectious inflammation, such as non-infectious enteritis, non-infectious pneumonia, infantile non-infectious diarrhea and the like in the research of years of clinical practice. Non-infectious inflammation, which is not caused by microbial infection, is poor in the therapeutic effect of conventional anti-inflammatory drugs, such as antibiotics.

Preferably, the drug prepared from kalimeris indica for treating radiation enteritis has remarkable curative effect. Specifically, for acute radiation enteritis, diarrhea can be stopped after taking the kalimeris indica extract for 1 day, so that the symptoms of radiation enteritis can be prevented from being continued and developing into chronic intestinal injury; for subacute radiation enteritis, the patient can take the kalimeris indica extract for 2-5 days to stop diarrhea, stop intestinal bleeding and relieve abdominal pain. At present, the treatment course of the radiation enteritis in the current stage is longer in western medicine or traditional Chinese medicine, and the effect can be gradually shown after 7 days in the shortest case. Therefore, the kalimeris indica can greatly shorten the treatment period of radiation enteritis, quickly relieve the physiological pain of patients and eliminate the psychological panic and worry of the patients. Moreover, the rapid repair of the intestinal mucosa can quickly recover the intestinal nutrition of the patient, promote the recovery of the intestinal function and provide good nutrition supply for the patient to overcome the diseases.

Therefore, the medicine can greatly shorten the treatment period of the radiation enteritis, quickly relieve the physiological pain of patients and eliminate the psychological panic and worry of the patients. Moreover, the rapid repair of the intestinal mucosa can enable a patient to recover the intestinal nutrition as soon as possible, promote the recovery of the intestinal function and provide good nutrition supply for the patient to overcome diseases, thereby effectively solving the problems of long treatment period, poor curative effect and low tolerance of the patient in the current stage of radiation enteritis.

Further, the medicine comprises the kalimeris indica extract and a pharmaceutically acceptable carrier or auxiliary material.

In order to allow the drug to release the active ingredient rapidly, continuously and over a long period of time, the drug of the present invention may be manufactured according to conventional methods disclosed in the art. The route of administration of the medicament of the present invention is oral, nasal inhalation, or parenteral administration. The pharmaceutical preparation can be in the form of powder, granule, tablet, emulsion, syrup, aerosol, soft capsule, hard capsule, sterile injection, sterile powder, etc.

Preferably, in a preferred embodiment of the present invention, the pharmaceutical formulation is an oral formulation. The active ingredients in the herba Kalimeridis extract in the medicine are mostly substances with relatively high polarity, and the medicine has high solubility in water phase, and can be easily made into various oral preparations, such as powder, granule, tablet, emulsion, syrup, capsule, etc. More preferably, the medicament containing the Kalimeris indica extract is preferably taken with a large amount of water, and is preferably formulated into oral liquid or granule.

It is emphasized that the medicament can be administered alone or in combination with other medicaments; the medicine can be a single preparation with the active ingredients only containing the kalimeris indica extract, or a compound preparation with the active ingredients containing the kalimeris indica extract and other medicines, such as a compound preparation prepared together with certain antitumor medicines.

Herein, the term "pharmaceutically acceptable" means that the compound is physiologically acceptable when the compound is administered to a human, and that systemic anaphylaxis including anaphylaxis such as gastrointestinal disorders, dizziness, and the like, or the like, is excluded.

In the present invention, "pharmaceutically acceptable carrier" includes, but is not limited to: binders (such as microcrystalline cellulose, alginates, gelatin, and polyvinylpyrrolidone), fillers (such as starch, sucrose, glucose, and anhydrous lactic acid), disintegrants (such as crosslinked PVP, sodium crosslinked carboxymethyl starch, sodium crosslinked carboxymethyl cellulose, and low-substituted hydroxypropyl cellulose), lubricants (magnesium stearate, aluminum stearate, talc, polyethylene glycol, sodium benzoate), wetting agents (such as glycerin), surfactants (such as cetyl alcohol), and absorption enhancers, flavors, sweeteners, diluents, coating agents, and the like.

Furthermore, the kalimeris indica extract in the medicine is obtained by treating kalimeris indica by adopting a solvent extraction method, and a solvent system used in the solvent extraction method is a water-soluble organic solvent mixed system.

Since the active ingredients for treating radiation enteritis in the kalimeris indica medicinal material are mainly large polar substances, a water-water soluble organic solvent mixed system is adopted to extract the kalimeris indica medicinal material, which is beneficial to improving the dissolution rate of medicinal substances. Preferably, the water-soluble organic solvent includes at least one of water-soluble alcohol, ether, ketone and amide. It should be noted that, in order to avoid the structural change of the active ingredients in kalimeris indica, no ironware can be used in the whole process of solvent extraction, post-treatment and preparation of the preparation.

Preferably, the solvent extraction method includes soaking, percolating, decocting, heating and refluxing, ultrasonic oscillating, and microwave extraction. It is emphasized that, since the active ingredients of the Kalimeris indica for treating radiation enteritis are mainly large polar substances, the Kalimeris indica cannot be washed with a large amount of water before extraction, so as to avoid loss of effective substances.

More preferably, the extraction method is a heating reflux extraction method, and more particularly, the preparation method of the kalimeris indica extract comprises the following steps: heating and refluxing herba Kalimeridis with 45-55 wt% ethanol solution at 75-90 deg.C for 2-3 h, filtering, heating and refluxing the obtained residue with 45-55 wt% ethanol solution at 75-90 deg.C for 1-2 h, mixing the filtrates obtained by two-time extraction, and concentrating under reduced pressure to obtain herba Kalimeridis extract.

More preferably, the kalimeris indica extract is obtained after the kalimeris indica is extracted by adopting a solvent extraction method; and then, extracting the kalimeris indica extracting solution by using a low-polarity solvent to obtain a large-polarity part, namely the kalimeris indica extract. The specific process comprises the following steps: and removing the organic solvent in the obtained herba Kalimeridis extract, reserving a water phase, adding a certain volume of low-polarity solvent into the water phase for extraction, extracting for 2-3 times, and concentrating the obtained water phase under reduced pressure to obtain the herba Kalimeridis extract. The small polar substances in the herba Kalimeridis extract are removed by extracting the herba Kalimeridis extract, and the content of the effective substances in the prepared herba Kalimeridis extract is increased, so that the drug effect is further improved. More preferably, the low-polarity solvent includes one or more of petroleum ether, n-hexane, cyclohexane, benzene, dichloromethane, chloroform, diethyl ether and gasoline.

In certain embodiments of the invention, the extract of kalimeris indica is obtained by mixing kalimeris indica with a water-water soluble organic solvent, grinding and filtering. After grinding, the juice obtained by filtration is subjected to a simple conventional treatment to obtain the Kalimeris indica extract.

The real-time mode also provides a medicament for treating non-infectious inflammation, which comprises the kalimeris indica extract and a pharmaceutically acceptable carrier or auxiliary material. The medicine has good curative effect on non-infectious inflammation, can greatly shorten the treatment period of non-infectious inflammation, and improve the tolerance of patients.

The features and properties of the present invention are further described in detail below with reference to examples:

example 1

The embodiment provides a medicine for treating radiation enteritis, which is an oral liquid and a preparation method thereof, wherein the preparation method comprises the following steps:

1kg of fresh Kalimeris indica whole grass is quickly cleaned, the root of the Kalimeris indica is carried with silt, and the Kalimeris indica whole grass is cut into sections. Decocting with water 5L in glass container, boiling, keeping slightly boiling for 30min, pouring out the liquid medicine, adding appropriate amount of antiseptic, subpackaging, 250 mL/bottle, and making into oral liquid with content of fresh medicinal material of about 200 g/L. One bottle at a time, and is swallowed slowly, and taken within 1 hour. It is administered 3 times daily.

Example 2

The embodiment provides a medicine for treating radiation enteritis, which is a granule preparation, and the preparation method comprises the following steps:

drying herba Kalimeridis 10kg, pulverizing into coarse powder, extracting with 80L 50% ethanol under heating in a stainless steel extraction tank, refluxing for 2 hr, and filtering to obtain extractive solution. The residue was extracted with 50L of 50% ethanol under reflux for 1 hour, and filtered to obtain an extract. Mixing the two extractive solutions, and recovering ethanol under reduced pressure until no alcohol smell exists to obtain about 55L concentrated solution. The concentrate was extracted twice with petroleum ether, each time in an amount of 1/2 volumes of concentrate. The aqueous phase was separated and concentrated to 10L by the open.

Mixing 5kg of glucose and 4kg of sucrose uniformly to be used as an absorbent; spraying herba Kalimeridis concentrated solution with absorbent as fluidized bed material by fluidized bed granulator. The dry particles are subpackaged according to 10 g/bag, which is about equal to 10g dry medicinal materials/bag. One bag each time, dissolving with 200mL warm water, and taking 2 times per day within 0.5 hr.

Example 3

The embodiment provides a medicine for treating radiation enteritis, which is a powder preparation and a preparation method thereof, wherein the preparation method comprises the following steps:

drying 6kg of herba Kalimeridis, crushing into coarse powder, fully wetting with methanol, putting into a stainless steel percolation cylinder, adding methanol to immerse the medicinal materials, soaking overnight, percolating with 60L of methanol at a percolate flow rate of about 30mL/min, collecting percolate, recovering methanol from the percolate until the percolate is dry, dispersing and suspending the extract with 1000mL of deionized water, and extracting with dichloromethane for three times with the dosage of 400mL each time. The aqueous phase was separated and concentrated to 5L by the open.

2.5kg of glucose was dissolved in the concentrate and spray dried. And 5g of the dry powder is subpackaged into 10g of dry medicinal materials per bag. One bag at a time, dissolved in 250mL warm water, and taken over 1 hour. 3 times daily.

Test example 1

The efficacy of the kalimeris indica provided by the invention in the treatment of radiation enteritis is evaluated in combination with animal tests.

Test animals: 48 SPF SD rats aged 6-8 weeks and weighing 220 +/-20 g are bred under the SPF condition. After adaptive feeding for 7 days, the animals were randomly divided into 5 groups, namely 8 normal control groups, and 10 model control groups, drug low-dose groups, drug medium-dose groups and drug high-dose groups.

Except for the normal control group, rats in other groups are fasted and are not forbidden to be water for 12-14 h, 3% sodium pentobarbital is injected under the peritoneum for anesthesia, then the rats are fixed on an operation plate, the rats are irradiated on the whole belly by an X-ray linear accelerator, the irradiation dose is 9Gy, and the irradiation time is 3 min. From the second day after irradiation, each rat was gavaged 1 time a day for 3 consecutive days and observed for 30 days.

The normal control group and the model control group are filled with normal saline, and the filling volume is 10mL/kg body weight. The ethanol extract of the medicinal material of the low, medium and high dosage groups of the gastric lavage malan comprises the following extraction methods: heating and extracting herba Kalimeridis with 50% ethanol, refluxing for 2 hr, and separating extractive solution; extracting the residue with 50% ethanol under reflux for 1 hr, separating extractive solutions, mixing the two extractive solutions, concentrating under reduced pressure to obtain extract, and dissolving with 1% Tween-80 aqueous solution. The gavage dose of the drug low dose group is 1.25g dry medicinal materials/kg body weight; the intragastric administration dosage of the drug medium dosage group is 2.5g dry medicinal materials/kg body weight; the gavage dose of the drug high dose group was 5g dry drug/kg body weight.

The test results show that except the normal control group, the other animals in each group have the phenomenon of stool character change in the next day after irradiation, and the phenomenon is mainly shown as follows: mucus and thin stool. The mental state of the model control group is the worst 3-7 days after irradiation, most of the model control group has mucus and bloody stool, diet and activity are little, the body shape is gradually thinned, 3 mice die in 7 days, the state of the rest mice is gradually improved, and the mental state is close to that of the normal group after 20 days after irradiation. The low-dose group stops diarrhea and hematochezia on the 4 th day after irradiation, then gradually increases diet and activity, and restores the normal state of excrement on the 7 th day after irradiation; the diarrhea and hematochezia of the medium-high dose group of the medicine are stopped on the 3 rd day after irradiation, the diet and activity increase day by day, and the stool returns to normal on the 5 th day after irradiation; after the feces return to normal, the mental state of the low, medium and high drug dose groups gradually improved, the body weight gradually recovered and increased, and none of the three groups died. Therefore, the herba Kalimeridis extract provided by the invention has a remarkable curative effect in treating radiation enteritis.

Test example 2

The efficacy of the Kalimeris indica extract provided by the present invention in terms of non-infectious inflammation is evaluated in combination with clinical trials.

Case one:

song Dynasty, female, age 45, advanced forms of poorly differentiated adenocarcinoma of the rectum, metastasized to the uterine, ovarian and pelvic lymph nodes. Preoperative chemotherapy was performed, 5 times per week with chemotherapy being given every 2 weeks. After the second week of radiotherapy, mucus and stool appear in the stool, and symptoms such as nausea, abdominal pain, abdominal distension and frequent defecation appear. After the 15 th radiotherapy, just after the 3 rd chemotherapy is finished, the stool frequency is suddenly increased to nearly thirty times a day, which is similar to incontinence, a large amount of undigested food in the stool, burning pain of the anus, thirst and no urine, and watery diarrhea occurs after drinking water, so that the digestive tract loses the water absorption function. The oral administration of Gegenqinlian tablet is ineffective for two days.

Then, about 50g of herba Kalimeridis is adopted, about 500mL of water is added for decoction, the decoction is kept slightly boiled for 30min after boiling, the liquid medicine is taken, the liquid medicine is cooled to about 45 ℃ and is drunk, and the liquid medicine is drunk within half an hour. After 2 hours, the number of stools decreased, about 8-9 times a day, with urine. If the water decoction of the fresh kalimeris indica is drunk in the next day, the number of times of defecation is reduced to 4-5 times per day, mucus in the stool is reduced, abdominal pain is relieved, urine is normal, and there is a desire to take food. After the administration, the patient does not take the food any more, undigested food in the stool gradually decreases, and the appetite returns to normal on day 4, and the stool returns to normal on day 5.

Case two

Populus, female, 56 years old, cervical cancer metastasized pelvic lymph node, post-operative pelvic radiation therapy 5 times per week. Acute enteritis symptoms such as abdominal pain, abdominal distension, stool frequency increase, mucus stool and the like appear during radiotherapy, the symptoms are controlled by taking glutamine capsules and Mipida montmorillonite powder, and after the radiotherapy is finished, the acute radiation enteritis is gradually self-healed. But 3 months after the radiotherapy, abdominal pain, tenesmus and repeated diarrhea and bloody stool appear. The oral administration of the Simmadia montmorillonite powder combines gentamicin and dexamethasone for clystering, the patient does not get better for one week, and the patient does not want to receive clystering again. Taking 20g of herba Kalimeridis dry whole herb, cutting into sections, adding about 300mL of water, decocting, boiling, keeping slightly boiling for 30min, and pouring out the liquid medicine; decocting the residue with 200mL water, boiling, keeping boiling for 15min, and collecting the decoction. Mixing the two medicinal liquids, cooling to about 45 deg.C, and drinking within 1 hr. Twice a day. Continuously taking herba Kalimeridis decoction for 3 days, and stopping taking the medicine. On day 3, the abdominal pain and abdominal distension and the feeling of anal pendant are relieved, the frequency of defecation and hematochezia are reduced, and mucus in the defecation is also reduced; on day 5, no hematochezia was visible, and stools were normal.

While particular embodiments of the present invention have been illustrated and described, it would be obvious that various other changes and modifications can be made without departing from the spirit and scope of the invention. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this invention.

Claims (6)

1. Use of Indian Kalimeris herb (L.) of Indian Kalimeris indica (L.) of Compositae, Sch. Bip, as the sole active substance in the preparation of a medicament for the treatment of non-infectious inflammation, such as radiation enteritis.

2. Use of an extract of Kalimeris indica, which is a whole plant of Kalimeriis indica (L.) of Compositae, Sch.Bip, as the sole active substance in the manufacture of a medicament for the treatment of non-infectious inflammation, which is radiation enteritis, by treating Kalimeriana indica with a solvent extraction process using water, aqueous ethanol or methanol system.

3. The use according to claim 2, wherein the kalimeris indica extract is obtained after extraction of the kalimeris indica by solvent extraction; and then, extracting the kalimeris indica extracting solution by using a low-isopolar solvent, wherein the low-isopolar solvent is petroleum ether or dichloromethane, and the obtained large-polarity part is the kalimeris indica extract.

4. The use of claim 2, wherein the extract of kalimeris indica is obtained by mixing kalimeris indica with water, aqueous ethanol or methanol, grinding and filtering.

5. The medicine is characterized by being prepared from Indian Kalimeris (Kalimeris indica (L.) Sch. Bip) of Compositae or Indian Kalimeris (L.) extract, and pharmaceutically acceptable carriers or auxiliary materials, wherein the Indian Kalimeris extract is obtained by treating Indian Kalimeris (L.) of Compositae with a solvent system of water, aqueous ethanol or methanol.

6. The medicament for treating noninfectious inflammation according to claim 5, wherein the dosage form of the medicament is oral liquid.