CN112546182A

CN112546182A - Fucoidin composite preparation and preparation method and application thereof

Info

Publication number: CN112546182A
Application number: CN202011610828.0A
Authority: CN
Inventors: 孙占一; 邱霞; 姜进举; 刘书英; 张健; 李可昌; 王发合; 徐英真; 刘平平
Original assignee: Qingdao Mingyue Algae Bio Health Technology Co ltd
Current assignee: Qingdao Mingyue Algae Bio Health Technology Co ltd
Priority date: 2020-12-30
Filing date: 2020-12-30
Publication date: 2021-03-26

Abstract

The invention provides a fucoidin composite preparation and a preparation method and application thereof. The invention comprises the following raw materials: 40-80 parts of fucoidin, 4-16 parts of turmeric, 1-18 parts of aronia serrulata fruit powder, 1-18 parts of grape seed extract, 1-10 parts of lactobacillus casei and 1-10 parts of bifidobacterium lactis; the invention also provides a preparation method of the fucoidin composite preparation and application of the fucoidin composite preparation in preparing a medicine for relieving side effects of tumor radiotherapy and chemotherapy. The fucoidin has the functions of resisting inflammation, improving the immunity of the organism and improving the malnutrition, the turmeric has the anti-inflammatory function, the aronia serrulata fruit powder and the grape seed extract have the antioxidation function, and the components are scientifically matched, so that the side effects of low immunity, gastrointestinal dysfunction, inappetence, hypodynamia and the like caused by radiotherapy and chemotherapy of tumor patients can be effectively relieved, the side effects of attenuation and synergism are realized, the nutritional status of the patients is improved by regulating the levels of hunger essence and leptin in vivo, and the rehabilitation is facilitated.

Description

Fucoidin composite preparation and preparation method and application thereof

Technical Field

The invention relates to the technical field of biological medicines, in particular to a fucoidin composite preparation and a preparation method and application thereof.

Background

At present, the total number of the existing tumor patients in China exceeds 2000 thousands, every year, new tumor cases are 429 thousands of people, and death is 281 thousands of people, and 1 of 65 people are tumor patients. The causes of the tumor include gene factors and external factors, wherein the gene factors account for less than 10%, and the external factors include alcohol, smoking, obesity, diet, infection and the like. At present, the tumor treatment mode in China is mainly surgical treatment, radiotherapy and chemotherapy, wherein the radiotherapy and the chemotherapy can cause serious damage to normal cells of an organism, particularly immune cells, while killing tumor cells in a patient body, so that serious side effects are generated; these side effects include hypoimmunity, gastrointestinal dysfunction, loss of appetite, weakness, etc., which have serious effects on the recovery and quality of life of the patient.

Fucoidan, also called fucoidan and fucoidan, is a functional polysaccharide substance derived from sea, mainly existing in brown algae such as kelp, Undaria pinnatifida, and Nemacystus decipiens, and is a macromolecular composite polysaccharide containing sulfate group and fucose. In recent years, researches find that the fucoidin can effectively relieve the side effects of tumor radiotherapy and chemotherapy, relieve inflammatory reactions caused by radiotherapy and chemotherapy, improve the immunity of the organism, improve the effect of radiotherapy and chemotherapy and help the recovery of tumor patients. Because the body condition of a tumor patient is complex, side effects caused by radiotherapy and chemotherapy are various, and the single fucoidin has limited effect when relieving the side effects of the tumor radiotherapy and chemotherapy, and cannot help the tumor patient to recover well.

Disclosure of Invention

The invention aims to provide a fucoidin composite preparation, a preparation method and application thereof, and aims to solve the problem that single fucoidin can not well help tumor patients to recover when the side effect of tumor radiotherapy and chemotherapy is relieved.

In order to solve the technical problem, the technical scheme of the invention is realized as follows:

in one aspect, the fucoidin composite preparation contains the following raw materials in parts by weight: 40-80 parts of fucoidin, 4-16 parts of turmeric, 1-18 parts of aronia serrulata fruit powder, 1-18 parts of grape seed extract, 1-10 parts of lactobacillus casei and 1-10 parts of bifidobacterium lactis.

The fucoidin in the fucoidin composite preparation has the functions of resisting inflammation, improving the immunity of the organism and improving the malnutrition condition, the turmeric has the function of resisting inflammation, the aronia serrulata fruit powder and the grape seed extract have the function of resisting oxidation, and the lactobacillus casei and the bifidobacterium lactis have the functions of regulating the intestinal flora and improving the immunity; the functional raw materials such as fucoidin, turmeric, aronia fruit powder and grape seed extract are matched with lactobacillus casei and bifidobacterium lactis, the components are scientifically matched, supplement each other and mutually promote, and the nutritional status of a patient is improved by adjusting the levels of ghrelin and leptin in a body; the level of inflammatory factors such as interleukin-6, interleukin-17 and the like in vivo is obviously reduced, and the incidence of radiotherapy inflammation is obviously reduced; reducing the level of matrix metalloproteinase MMP-9 tumor-related indexes, and enhancing the treatment effect of radiotherapy and chemotherapy; the composition is used for preparing the medicine for relieving the side effects of tumor radiotherapy and chemotherapy, plays a role in attenuation and synergism, can effectively relieve the side effects of low immunity, gastrointestinal dysfunction, inappetence, hypodynamia and the like of tumor patients during radiotherapy and chemotherapy, is beneficial to the recovery of the tumor patients, and improves the life quality of the patients.

As a preferred embodiment, the feed comprises the following raw materials in parts by weight: 50-70 parts of fucoidin, 5-15 parts of turmeric, 5-15 parts of aronia serrulata fruit powder, 5-15 parts of grape seed extract, 1-5 parts of lactobacillus casei and 1-5 parts of bifidobacterium lactis.

In the invention, the main component of the fucoidin is L-fucose, and also comprises various monosaccharides such as L-arabinose, D-xylose, D-mannose, D-glucose, D-galactose and the like, and the fucoidin has the physiological effects of regulating immunity in two directions, eliminating free radicals, resisting aging, resisting blood coagulation and thrombus, resisting tumor and HIV virus, eliminating gastrointestinal system disorder, resisting allergy, enhancing liver function, reducing hyperlipidemia and hypertension, stabilizing blood sugar level, promoting skin regeneration, moisturizing skin and the like, and has more than 20 items.

In the invention, the turmeric is pungent in nature, bitter in taste, slightly warm and enters spleen and liver meridians; can promote qi circulation, remove blood stasis, dredge meridians and relieve pain; it can be used for treating abdominal distention and pain, shoulder pain, pain in arm, heart pain, puerperal blood pain, skin sore, tinea, menoxenia, amenorrhea, and traumatic injury.

In the invention, the aronia melanocarpa contains abundant vitamins, minerals, antioxidants and other important polyphenols which have the effect of resisting cancer cells; the wild cherry fruit powder is prepared from wild cherry by sun drying, baking and grinding.

The grape seed extract is an effective active nutrient component extracted from natural grape seeds, contains novel efficient natural antioxidant substances which cannot be synthesized in human bodies, is a substance with strongest capacities of resisting oxidation and removing free radicals, can effectively remove redundant free radicals in human bodies, has super-strong functions of delaying senescence and enhancing immunity, and has the functions of resisting oxidation, resisting allergy, resisting fatigue, enhancing physique, improving sub-health state, delaying senescence, improving dysphoria, irritability, dizziness, weakness, hypomnesis and the like.

In the invention, the Lactobacillus casei belongs to Lactobacillus, is gram-positive bacteria, does not produce spores, flagellum and motion, facultative heterotypic fermentation lactose and does not liquefy gelatin; the optimal growth temperature is 37 ℃, and the G + C content is 45.6-47.2%; the thalli are different in length, and the two ends of the thalli are square and are often chained; the bacterial colony is coarse, grey white and sometimes yellowish, can ferment various sugars, helps digestion, prevents constipation and cell aging, resists tumor and regulates human body functions.

In the present invention, bifidobacterium lactis is an anaerobic bacterium which is lactic acid-producing, gram-positive, non-sporulating and immotile, is a physiological bacterium species which can promote the health of the body, and has various functions, for example, treatment of chronic diarrhea, relief of constipation, inhibition of cancer, protection of the liver, and the like.

As a preferred embodiment, the feed comprises the following raw materials in parts by weight: 60 parts of fucoidin, 10 parts of turmeric, 10 parts of aronia serrulata fruit powder, 10 parts of grape seed extract, 5 parts of lactobacillus casei and 5 parts of bifidobacterium lactis. The invention can further optimize the weight parts of the fucoidin, the turmeric, the aronia serrulata fruit powder, the grape seed extract, the lactobacillus casei and the bifidobacterium lactis, further reduce the cost of raw materials and improve the comprehensive effect of the fucoidin composite preparation in relieving the side effect of tumor patients in the chemoradiotherapy process.

As a preferred embodiment, the fucoidan has a purity of not less than 80% and the grape seed extract has a purity of not less than 80%. The purity of the fucoidin is more than 80%, and the content of effective components in the fucoidin is fully ensured so as to ensure the efficacy of the fucoidin composite preparation; the fucoidin and the grape seed extract are both mature products sold in the market, the purity of the grape seed extract is also over 80 percent, and the purity of the grape seed extract is controlled, so that the content of effective components in the grape seed extract is controlled, and the efficacy of the fucoidin composite preparation is fully ensured.

In a preferred embodiment, the turmeric is prepared by sun-drying, baking and grinding turmeric, and the aronia fruit powder is prepared by sun-drying, baking and grinding aronia. The processing method of the turmeric of the invention is simple, is beneficial to fully retaining the effective components in the turmeric, and is convenient for realizing industrialization; meanwhile, the processing method of the wild cherry berry powder is convenient, and is beneficial to fully retaining the effective components in the wild cherry berry, thereby ensuring the efficacy of the fucoidin composite preparation.

As a preferred embodiment, the number of the bacteria of the Lactobacillus casei is not less than 1 × 10¹⁰CFU/g, the number of the bacteria of the bifidobacterium lactis is not less than 1 multiplied by 10¹⁰CFU/g. The lactobacillus casei and the bifidobacterium lactis are mature products sold in the market, and the number of the lactobacillus casei and the bifidobacterium lactis in the two strains is not less than 1 multiplied by 10¹⁰CFU/g, has effects of regulating intestinal flora and enhancing immunity.

In another aspect, the present invention provides a method for preparing a fucoidan composition preparation, comprising the steps of: mixing fucoidin, Curcuma rhizome, Prunus serrulata fruit powder, grape seed extract, Lactobacillus casei and Bifidobacterium lactis, stirring for 20-40min, packaging, and sealing to obtain fucoidin composition.

The preparation method of the fucoidin composite preparation is simple, convenient to operate, free of special requirements for equipment, high in production efficiency, low in production cost and beneficial to realization of industrialization; the preparation conditions are mild, and the effective components in the fucoidin, the turmeric, the aronia melanocarpa fruit powder, the grape seed extract, the lactobacillus casei and the bifidobacterium lactis can be fully reserved, so that the effect of the fucoidin composite preparation is ensured.

In a further aspect, the invention relates to an application of a fucoidin composition preparation, and an application of the fucoidin composition preparation in preparing a medicine for relieving side effects of tumor radiotherapy and chemotherapy.

The fucoidin composite preparation can be used for relieving the side effects of tumor radiotherapy and chemotherapy, can effectively relieve the side effects of low immunity, gastrointestinal dysfunction, inappetence, hypodynamia and the like caused by the radiotherapy and chemotherapy of tumor patients, is beneficial to the recovery of the patients, and improves the life quality of the tumor patients.

As a preferred embodiment, the content of the effective component of the medicine is 5-99%. The fucoidan combined preparation of the present invention can be used as an active ingredient, and can be combined with pharmaceutically acceptable carriers, such as: lubricant, filler, adhesive, disintegrant, solubilizer or stabilizer, and making into various dosage forms.

As a preferred embodiment, the pharmaceutical formulation is in the form of tablets, granules, capsules, pills, syrups, suspensions or pastes. The medicine for relieving the side effect of the tumor radiotherapy and chemotherapy, which is prepared from the fucoidin composite preparation, has a plurality of dosage forms, thereby meeting different requirements of patients.

Compared with the prior art, the invention has the beneficial effects that: the fucoidin in the fucoidin composite preparation has the functions of resisting inflammation, improving the immunity of the organism and improving the malnutrition condition, the turmeric has the function of resisting inflammation, the aronia serrulata fruit powder and the grape seed extract have the function of resisting oxidation, and the lactobacillus casei and the bifidobacterium lactis have the functions of regulating the intestinal flora and improving the immunity; the functional raw materials such as fucoidin, turmeric, aronia fruit powder and grape seed extract are matched with lactobacillus casei and bifidobacterium lactis, the components are scientifically matched, supplement each other and mutually promote, and the nutritional status of a patient is improved by adjusting the levels of ghrelin and leptin in a body; the level of inflammatory factors such as interleukin-6, interleukin-17 and the like in vivo is obviously reduced, and the incidence of radiotherapy inflammation is obviously reduced; reducing the level of matrix metalloproteinase MMP-9 tumor-related indexes, and enhancing the treatment effect of radiotherapy and chemotherapy; the composition is used for preparing the medicine for relieving the side effects of tumor radiotherapy and chemotherapy, plays a role in attenuation and synergism, can effectively relieve the side effects of low immunity, gastrointestinal dysfunction, inappetence, hypodynamia and the like of tumor patients during radiotherapy and chemotherapy, is beneficial to the recovery of the tumor patients, and improves the life quality of the patients. The preparation method of the fucoidin composite preparation is simple, is convenient to operate, has no special requirements on equipment, and is beneficial to realizing industrialization; the preparation conditions are mild, and the effective components in the fucoidin, the turmeric, the aronia melanocarpa fruit powder, the grape seed extract, the lactobacillus casei and the bifidobacterium lactis can be fully reserved, so that the effect of the fucoidin composite preparation is ensured.

Detailed Description

The technical solutions of the present invention will be described clearly and completely with reference to specific embodiments of the present invention, and it should be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

The invention relates to a fucoidin composite preparation, which comprises the following raw materials in parts by weight: 40-80 parts of fucoidin, 4-16 parts of turmeric, 1-18 parts of aronia serrulata fruit powder, 1-18 parts of grape seed extract, 1-10 parts of lactobacillus casei and 1-10 parts of bifidobacterium lactis.

Preferably, the feed comprises the following raw materials in parts by weight: 50-70 parts of fucoidin, 5-15 parts of turmeric, 5-15 parts of aronia serrulata fruit powder, 5-15 parts of grape seed extract, 1-5 parts of lactobacillus casei and 1-5 parts of bifidobacterium lactis.

Further, the feed comprises the following raw materials in parts by weight: 60 parts of fucoidin, 10 parts of turmeric, 10 parts of aronia serrulata fruit powder, 10 parts of grape seed extract, 5 parts of lactobacillus casei and 5 parts of bifidobacterium lactis.

Preferably, the purity of the fucoidan is not less than 80%, and the purity of the grape seed extract is not less than 80%.

Preferably, the turmeric is prepared by sun-drying, baking and grinding turmeric, and the aronia melanocarpa fruit powder is prepared by sun-drying, baking and grinding aronia melanocarpa.

Preferably, the number of the lactobacillus casei is not less than 1 × 10¹⁰CFU/g, the number of the bacteria of the bifidobacterium lactis is not less than 1 multiplied by 10¹⁰CFU/g。

The invention relates to a preparation method of a fucoidin composite preparation, which comprises the following steps: mixing fucoidin, Curcuma rhizome, Prunus serrulata fruit powder, grape seed extract, Lactobacillus casei and Bifidobacterium lactis, stirring for 20-40min, packaging, and sealing to obtain fucoidin composition.

The invention relates to an application of a fucoidin composite preparation, in particular to an application of the fucoidin composite preparation in preparing a medicine for relieving side effects of tumor radiotherapy and chemotherapy.

Preferably, the content of the effective component of the medicine is 5-99%.

Preferably, the medicament is in the form of tablets, granules, capsules, pills, syrup, suspension or paste.

Example one

The invention relates to a preparation method of a fucoidin composite preparation, which comprises the following steps:

1) weighing the following raw materials in parts by weight: 80 parts of fucoidin, 16 parts of turmeric, 1 part of aronia serrulata fruit powder, 1 part of grape seed extract, 1 part of lactobacillus casei and 1 part of bifidobacterium lactis for later use;

2) putting the above raw materials into a mixer, mixing, and stirring for 30min to obtain a mixture;

3) taking out the mixture obtained in the step 2), sealing and subpackaging the mixture on an automatic subpackaging machine according to the specification, and packaging the mixture into a warehouse to obtain the fucoidin composite preparation.

Example two

1) weighing the following raw materials in parts by weight: 40 parts of fucoidin, 4 parts of turmeric, 18 parts of aronia serrulata fruit powder, 18 parts of grape seed extract, 10 parts of lactobacillus casei and 10 parts of bifidobacterium lactis for later use;

2) putting the above raw materials into a mixer, mixing, and stirring for 20min to obtain a mixture;

EXAMPLE III

1) weighing the following raw materials in parts by weight: 60 parts of fucoidin, 10 parts of turmeric, 10 parts of aronia serrulata fruit powder, 10 parts of grape seed extract, 5 parts of lactobacillus casei and 5 parts of bifidobacterium lactis for later use;

2) putting the above raw materials into a mixer, mixing, and stirring for 40min to obtain a mixture;

Comparative example 1

A preparation method of a lentinan composite preparation comprises the following steps:

1) weighing the following raw materials in parts by weight: 60 parts of lentinan, 10 parts of turmeric, 10 parts of aronia serrulata fruit powder, 10 parts of grape seed extract, 5 parts of lactobacillus casei and 5 parts of bifidobacterium lactis for later use;

3) taking out the mixture obtained in the step 2), sealing and subpackaging the mixture according to the specification on an automatic subpackaging machine, and packaging and warehousing to obtain the lentinan composite preparation.

Comparative example No. two

A preparation method of a ganoderan composite preparation comprises the following steps:

1) weighing the following raw materials in parts by weight: 60 parts of ganoderma lucidum polysaccharide, 10 parts of turmeric, 10 parts of aronia serrulata fruit powder, 10 parts of grape seed extract, 5 parts of lactobacillus casei and 5 parts of bifidobacterium lactis for later use;

3) taking out the mixture obtained in the step 2), sealing and subpackaging the mixture according to the specification on an automatic subpackaging machine, and packaging and warehousing to obtain the ganoderan composite preparation.

Comparative example No. three

A method for preparing a ginsenoside composition preparation comprises the following steps:

1) weighing the following raw materials in parts by weight: 60 parts of ginsenoside, 10 parts of turmeric, 10 parts of aronia serrulata fruit powder, 10 parts of grape seed extract, 5 parts of lactobacillus casei and 5 parts of bifidobacterium lactis for later use;

3) taking out the mixture obtained in the step 2), sealing and subpackaging the mixture according to the specification on an automatic subpackaging machine, and packaging and warehousing to obtain the ginsenoside composite preparation.

Comparative example No. four

A method for preparing a pure fucoidan preparation comprises the following steps:

1) taking 100 parts of fucoidin for later use;

3) taking out the mixture obtained in the step 2), sealing and subpackaging the mixture according to the specification on an automatic subpackaging machine, and packaging and warehousing to obtain the pure fucoidin preparation.

Experiment 1

Three parts of fucoidin combined preparation obtained in the first embodiment to the third embodiment of the invention and four parts of control preparation obtained in the first comparative embodiment to the fourth comparative embodiment are respectively used for lung radiotherapy population for functional evaluation, and relevant experimental schemes and data are as follows:

(1) experimental grouping and administration

The study population included 80 lung cancer patients who required radiotherapy, inclusion criteria included: the pathological or cytological examination shows that the lung cancer patients are clear, the lung cancer patients are 18 to 75 years old, the life expectancy is more than or equal to 3 months, the lung cancer patients have radiotherapeutic indications, and the lung cancer patients are not treated by other related tumors in about 3 months. In the study population, if patients suffering from severe barycenter, liver and renal insufficiency and other diseases affecting the steady vital signs, patients suffering from nervous and mental diseases, patients in gestation or lactation, patients with allergic constitution or allergic to various medicines or patients participating in other clinical trials at the same time, the experimental subject is excluded.

Randomly dividing the subjects into an experimental group, a control group and a blank group, wherein the patients in each group have no statistical difference, the experimental group is 3 groups, the fucoidan combined preparation of the example I, the example II and the example III is respectively adopted, the control group is 4 groups, the preparation of the comparative example I, the comparative example II, the comparative example III and the comparative example IV is respectively adopted, and the administration modes of the experimental group and the control group are as follows: during radiotherapy, 2 times a day, 2g each time, is taken with warm water; blank group, placebo is given daily, and during radiotherapy, 2 times a day, 2g each time, is taken with warm water.

All subjects receive conventional local radiotherapy of the lung, and irradiation fields are designed according to the principle that high-dose areas are concentrated in lesions and the surrounding normal tissues are protected to the maximum extent, wherein the number of the irradiation fields of a single target area is 3-5; the dose of 3D-CRT was 2 Gy/time, 1 time daily, 5 times per week for 4 weeks, and the full group prescribed dose ranged from 50-70 Gy.

(2) Evaluation of therapeutic index

Collecting 5-6mL of peripheral venous blood of a subject before and 1 week after radiotherapy, centrifuging at a speed of 2000r/min for 20min, separating serum, and determining the contents of ghrelin, leptin, interleukin-6 (IL-6), interleukin-17 (IL-17) and matrix metalloproteinase 9(MMP9) according to the instructions of an Elisa kit; meanwhile, a general cancer cause fatigue scale in the industry is filled, the fatigue duration, the influence of fatigue on work and life, the fatigue degree and the like of the patient are observed, the fatigue scoring condition of the patient during treatment is evaluated, and the incidence rate of the radiation pneumonitis is counted.

(3) Results of the experiment

TABLE 1 alleviation of side effects of pulmonary radiotherapy

As can be seen from the table 1, when the fucoidin composition preparation is used for relieving the side effect of a lung cancer patient in the radiotherapy process, in the related indexes of organism nutrition of a subject, the ghrelin content is 3.11-3.46pg/mL, and the leptin content is 3.01-3.25 npg/mL; however, when the comparative example I is used for relieving the side effect of the lung cancer patient in the radiotherapy process, the hunger content is 3.82pg/mL and the leptin content is 3.83npg/mL in the body nutrition related indexes of the subject; when the comparative example is used for relieving the side effect of the lung cancer patient in the radiotherapy process, the hunger essence content is 4.03pg/mL and the leptin content is 3.86npg/mL in the body nutrition related indexes of the subject; the comparative example is used for relieving the side effect of the lung cancer patient in the radiotherapy process, and the hunger essence content is 3.79pg/mL and the leptin content is 3.57npg/mL in the body nutrition related indexes of the subject; the fourth comparative example is used for relieving the side effect of the lung cancer patient in the radiotherapy process, and the hunger essence content is 3.66pg/mL and the leptin content is 3.28npg/mL in the body nutrition related indexes of the subject; in the radiotherapy process of a blank group of lung cancer patients, in the organism nutrition related indexes of a subject, the ghrelin content is 4.59pg/mL, and the leptin content is 3.94 npg/mL; therefore, when the fucoidin composition preparation is used for relieving the side effect of a lung cancer patient in the radiotherapy process, the ghrelin content and the leptin content of a subject can be obviously reduced, and the malnutrition phenomenon of the patient in the radiotherapy process is relieved; and the fucoidin composite preparation obtained by the invention has obviously better effect on relieving the malnutrition phenomenon of the patient in the radiotherapy process than the first comparative example, the second comparative example, the third comparative example and the fourth comparative example.

As shown in Table 1, when the fucoidin combination preparation is used for relieving the side effects of a lung cancer patient in a radiotherapy process, in the index of the body inflammatory factor of a subject, the content of interleukin-6 is 44.04-45.55pg/mL, and the content of interleukin-17 is 45.82-50.06 pg/mL; however, when the comparative example I is used for relieving the side effects of the lung cancer patient in the radiotherapy process, the interleukin-6 content is 50.26pg/mL and the interleukin-17 content is 63.84pg/mL in the body inflammatory factor index of the subject; when the comparative example is used for relieving the side effects of a lung cancer patient in the radiotherapy process, in the body inflammatory factor indexes of a subject, the content of interleukin-6 is 49.98pg/mL, and the content of interleukin-17 is 61.48 pg/mL; the comparative example three-purpose is used for relieving the side effect of the lung cancer patient in the radiotherapy process, and in the body inflammatory factor index of the subject, the content of interleukin-6 is 46.35pg/mL, and the content of interleukin-17 is 53.26 pg/mL; the fourth comparative example is used for relieving the side effects of the lung cancer patient in the radiotherapy process, and in the body inflammatory factor indexes of the subject, the content of interleukin-6 is 46.83pg/mL, and the content of interleukin-17 is 51.18 pg/mL; in the radiotherapy process of a blank group of lung cancer patients, in the body inflammatory factor indexes of a subject, the content of interleukin-6 is 52.38pg/mL, and the content of interleukin-17 is 66.21 pg/mL; therefore, when the fucoidin composite preparation is used for relieving the side effect of a lung cancer patient in the radiotherapy process, the interleukin-6 content and the interleukin-17 content of a subject can be obviously reduced, and the inflammatory reaction of the patient in the radiotherapy process is relieved; in addition, the fucoidin composite preparation obtained by the invention has obviously better effect on relieving the inflammatory reaction of the patient in the radiotherapy process than the first comparative example, the second comparative example, the third comparative example and the fourth comparative example.

As can be seen from the table 1, when the fucoidin composition preparation obtained by the invention is used for relieving the side effects of a lung cancer patient in the radiotherapy process, the content of matrix metalloproteinase-9, which is an organism tumor related index of a subject, is 34.05-36.25 pg/mL; however, in the case of the comparative example one for alleviating the side effects of the lung cancer patient during the radiotherapy, the matrix metalloproteinase-9 content, which is an index related to the body tumor, of the subject was 38.75 pg/mL; when the comparative example is used for relieving the side effects of the lung cancer patient in the radiotherapy process, the content of matrix metalloproteinase-9 which is the body tumor related index of the subject is 37.39 pg/mL; the comparative example three is used for relieving the side effect of the lung cancer patient in the radiotherapy process, and the content of matrix metalloproteinase-9 which is the body tumor related index of the subject is 36.88 pg/mL; the fourth comparative example is used for relieving the side effect of the lung cancer patient in the radiotherapy process, the content of matrix metalloproteinase-9 which is the body tumor related index of the subject is 36.32 pg/mL; in the radiotherapy process of a blank group of lung cancer patients, the content of matrix metalloproteinase-9 which is an organism tumor related index of a subject is 39.71 pg/mL; therefore, when the fucoidin composite preparation is used for relieving the side effect of a lung cancer patient in the radiotherapy process, the content of matrix metalloproteinase-9 of the patient can be obviously reduced, and the treatment effect of the radiotherapy and chemotherapy of the patient is enhanced; in addition, the fucoidin combination preparation obtained by the invention has obviously better effect than the first comparative example, the second comparative example, the third comparative example and the fourth comparative example in the aspect of enhancing the treatment effect of radiotherapy and chemotherapy of patients.

As can be seen from Table 1, when the fucoidin combination preparation obtained by the invention is used for relieving the side effects of the lung cancer patients in the radiotherapy process, the fatigue score of the subjects is 2.1-3.4; however, comparative example one was used to alleviate the side effects of lung cancer patients during radiation therapy, the subject had a fatigue score of 4.7 points; when the comparative example is used for relieving the side effect of the lung cancer patient in the radiotherapy process, the fatigue score of the subject is 4.5 points; the comparative example is used for relieving the side effect of the lung cancer patient in the radiotherapy process, and the fatigue score of the subject is 3.9 points; when the comparative example four is used for relieving the side effects of the lung cancer patient in the radiotherapy process, the fatigue score of the subject is 3.5 points; the fatigue score of the subjects in the course of radiotherapy of the blank group of lung cancer patients is 6.3 points; therefore, when the fucoidin composite preparation is used for relieving the side effect of a lung cancer patient in the radiotherapy process, the fatigue score of a subject can be remarkably reduced, and the phenomenon of hypodynamia of the patient in the radiotherapy process is relieved; in addition, the fucoidin composite preparation obtained by the invention has obviously better effect on relieving the hypodynamia of patients in the radiotherapy process than the first comparative example, the second comparative example, the third comparative example and the fourth comparative example.

As can be seen from Table 1, when the fucoidin composition preparation obtained by the invention is used for relieving the side effects of lung cancer patients in the radiotherapy process, the incidence rate of the radiation pneumonitis of the subjects is 20%; however, when comparative example one was used to alleviate the side effects of lung cancer patients during radiotherapy, the incidence of radiation pneumonitis in the subjects was 40%; when the comparative example is used for relieving the side effect of the lung cancer patient in the radiotherapy process, the incidence rate of the radiation pneumonitis of the subject is also 40%; the comparative example is used for relieving the side effect of the lung cancer patient in the radiotherapy process, and the incidence rate of the radiation pneumonitis of the subject is 30 percent; comparative example four when used to alleviate side effects of lung cancer patients during radiotherapy, the incidence of radiation pneumonitis in the subjects was also 30%; during the radiotherapy process of the lung cancer patients in the blank group, the incidence rate of the radiation pneumonitis of the subjects is 40%; therefore, when the fucoidin composite preparation is used for relieving the side effects of a lung cancer patient in the radiotherapy process, the incidence rate of radiation pneumonitis of a subject can be obviously reduced, and the incidence rate of symptoms of inflammation reaction, inappetence, fatigue and the like of the patient in the radiotherapy process can be relieved; in addition, the fucoidin composite preparation obtained by the invention has obviously better effect than the first comparative example, the second comparative example, the third comparative example and the fourth comparative example in the aspect of reducing the incidence rate of inflammatory reaction, inappetence, fatigue and other symptoms of patients in the radiotherapy process.

Experiment 2

Three parts of fucoidin combined preparation obtained in the first embodiment to the third embodiment of the invention and four parts of control preparation obtained in the first comparative embodiment to the fourth comparative embodiment are respectively used for intestinal tract radiotherapy population for functional evaluation, and relevant experimental schemes and data are as follows:

(1) experimental grouping and administration

The study population included 80 colon cancer patients who required radiotherapy, inclusion criteria included: pathological or cytological examination clearly shows that patients with colon cancer, between 18 and 75 years of age, have a life expectancy of 3 months or more, have radiotherapeutic indications, and have not been treated with other related tumors for nearly 3 months. In the study population, if patients suffering from severe barycenter, liver and renal insufficiency and other diseases affecting the steady vital signs, patients suffering from nervous and mental diseases, patients in gestation or lactation, patients with allergic constitution or allergic to various medicines or patients participating in other clinical trials at the same time, the experimental subject is excluded.

Randomly dividing the subjects into an experimental group, a control group and a blank group, wherein the patients in each group have no statistical difference, the experimental group is 3 groups, the fucoidan combined preparations of the first example, the second example and the third example are respectively adopted, the control group is 4 groups, the combined preparations of the first comparative example, the second comparative example, the third comparative example and the fourth comparative example are respectively adopted, and the administration methods of the experimental group and the control group are as follows: during radiotherapy, 2 times a day, 2g each time, is taken with warm water; blank group, placebo was given daily, and radiotherapy period was 2 times daily, 2g each time, and taken with warm water.

All subjects receive conventional intestinal local radiotherapy, and irradiation fields are designed according to the principle that high-dose areas are concentrated in lesions and the surrounding normal tissues are protected to the maximum extent, wherein the number of the irradiation fields of a single target area is 3-5. The dose of 3D-CRT was 2 Gy/time, 1 time daily, 5 times per week for 4 weeks, and the full group prescribed dose ranged from 50-70 Gy.

(2) Evaluation of therapeutic index

Before radiotherapy and 1 week after the radiotherapy is finished, 5-6mL of peripheral venous blood of a subject is collected, centrifuged at 2000r/min for 20min, serum is separated, and the contents of interleukin-6 (IL-6) and tumor necrosis factor (TNF-alpha) are determined according to the instructions of an Elisa kit. The clinical symptoms (abdominal pain score and hematochezia score) of the subjects are counted, meanwhile, a cancer-induced fatigue scale which is commonly used in the industry is filled, the fatigue duration, the influence of fatigue on work and life, the fatigue degree and the like of the patients are observed, the fatigue scoring condition of the patients during the treatment period is evaluated, and the incidence rate and the clinical total effective rate of the radiation enteritis of the subjects are counted.

(3) Results of the experiment

TABLE 2 alleviation of side effects of intestinal radiotherapy

As can be seen from the table 2, when the fucoidin combination preparation obtained by the invention is used for relieving the side effects of a colon cancer patient in the radiotherapy process, in the inflammation related indexes of a subject, the content of interleukin-6 is 53.48-56.18pg/mL, and the content of TNF-alpha is 28.86-33.01 pg/mL; however, in the case of the comparative example one for alleviating the side effects during the radiotherapy in the colon cancer patient, the interleukin-6 content was 59.83pg/mL and the TNF-. alpha.content was 37.62pg/mL in the inflammation-related index of the subject; the comparative example is used for relieving the side effect of a colon cancer patient in the radiotherapy process, and the interleukin-6 content is 60.82pg/mL and the TNF-alpha content is 38.59pg/mL in the inflammation related indexes of the subject; the comparative example is three-purpose, when the side effect of the colon cancer patient in the radiotherapy process is relieved, in the inflammation related indexes of the subjects, the content of interleukin-6 is 61.15pg/mL, and the content of TNF-alpha is 39.76 pg/mL; the fourth comparative example is used for relieving the side effects of the colon cancer patient in the radiotherapy process, and the interleukin-6 content is 56.83pg/mL and the TNF-alpha content is 34.81pg/mL in the inflammation related indexes of the subjects; in the blank group of colon cancer patients, in the process of radiotherapy, in the inflammation related indexes of the subjects, the content of interleukin-6 is 65.50pg/mL, and the content of TNF-alpha is 42.19 pg/mL. Therefore, when the fucoidin composite preparation is used for relieving the side effect of a colon cancer patient in the radiotherapy process, the interleukin-6 content and the TNF-alpha content of a subject can be obviously reduced, and the inflammatory reaction of the patient in the radiotherapy process is relieved; in addition, the fucoidin composite preparation obtained by the invention has obviously better effect on relieving the inflammatory reaction of the patient in the radiotherapy process than the first comparative example, the second comparative example, the third comparative example and the fourth comparative example.

As shown in Table 2, when the fucoidin combination preparation is used for relieving the side effects of colon cancer patients in the radiotherapy process, the abdominal pain scores of the subjects are all 1.0-1.3, and the hematochezia scores are all 0.6-1.0; however, when the comparative example one was used to alleviate the side effects of the colon cancer patients during the course of radiotherapy, the subjects had an abdominal pain score of 1.6 and a hematochezia score of 1.4; when the comparative example is used for relieving the side effects of a colon cancer patient in the radiotherapy process, the abdominal pain score of a subject is 1.7, and the hematochezia score is 1.4; the comparative example is used for relieving the side effect of the colon cancer patient in the radiotherapy process, the abdominal pain score of the subject is 1.6, and the hematochezia score is 1.3; when the comparative example four is used for relieving the side effects of a colon cancer patient in the radiotherapy process, the abdominal pain score of a subject is 1.4, and the hematochezia score is 1.1; in the course of radiotherapy, the subjects had an abdominal pain score of 1.8 and a hematochezia score of 1.6 for the colon cancer patients in the blank group. Therefore, when the fucoidin composite preparation is used for relieving the side effect of a colon cancer patient in the radiotherapy process, the abdominal pain score and the hematochezia score of a subject can be obviously reduced, and the incidence rate of clinical symptoms of abdominal pain, hematochezia and the like of the patient in the radiotherapy process is relieved; in addition, the fucoidin combination preparation obtained by the invention has obviously better effect on reducing clinical symptoms such as abdominal pain and hematochezia of a subject than the first comparative example, the second comparative example, the third comparative example and the fourth comparative example.

As can be seen from Table 2, when the fucoidin combination preparation obtained by the invention is used for relieving the side effect of rectal patients in the radiotherapy process, the fatigue score of the subjects is 2.6-4.0 points; however, when comparative example one was used to alleviate the side effects of the rectal cancer patient during radiation therapy, the subject had a fatigue score of 6.1 points; when the comparative example is used for relieving the side effect of the rectal cancer patient in the radiotherapy process, the fatigue score of the subject is 5.9 points; the comparative example is used for relieving the side effect of the rectal cancer patient in the radiotherapy process, and the fatigue score of the subject is 6.5 points; comparative example four when used to alleviate the side effects of a patient with rectal cancer during radiation therapy, the subject had a fatigue score of 4.3 points; the subjects had a fatigue score of 7.2 during the course of radiation therapy for the blank group of rectal cancer patients. Therefore, when the fucoidin composite preparation is used for relieving the side effect of a rectal cancer patient in the radiotherapy process, the fatigue score of a subject can be remarkably reduced, and the phenomenon of weakness of the patient in the radiotherapy process is relieved; in addition, the fucoidin composite preparation obtained by the invention has obviously better effect on relieving the hypodynamia of patients in the radiotherapy process than the first comparative example, the second comparative example, the third comparative example and the fourth comparative example.

As can be seen from the table 2, when the fucoidin composition preparation is used for relieving the side effects of colon cancer patients in the radiotherapy process, the incidence rate of radiation enteritis of the subjects is 20-30%; however, when comparative example one was used to alleviate the side effects of a colon cancer patient during radiation therapy, the incidence of radiation enteritis in the subject was 50%; when the comparative example is used for relieving the side effect of a colon cancer patient in the radiotherapy process, the incidence rate of radiation enteritis of the tested person is 50%; the comparative example three is used for relieving the side effect of a colon cancer patient in the radiotherapy process, and the incidence rate of radiation enteritis of a subject is 40 percent; comparative example four when used to alleviate side effects of a colon cancer patient during radiation therapy, the incidence of radiation enteritis in the subject was 40%; in the radiotherapy process of a blank group of colon cancer patients, the incidence rate of radiation enteritis of a subject is 50%; therefore, when the fucoidin composite preparation is used for relieving the side effect of a colon cancer patient in the radiotherapy process, the incidence rate of radiation enteritis of a subject can be obviously reduced, and the incidence rate of symptoms such as abdominal pain, hematochezia, inflammatory reaction and the like of the patient in the radiotherapy process can be relieved; in addition, the fucoidin composite preparation obtained by the invention has obviously better effect on relieving symptoms such as abdominal pain, hematochezia, inflammatory reaction and the like of a patient in the radiotherapy process than the first comparative example, the second comparative example, the third comparative example and the fourth comparative example.

As can be seen from the table 2, when the fucoidin composition preparation is used for relieving the side effects of colon cancer patients in the radiotherapy process, the clinical total effective rate of a subject is 80-90%; however, when the comparative example one is used for relieving the side effects of the colon cancer patient in the radiotherapy process, the clinical total effective rate of the subject is 70%; when the comparative example is used for relieving the side effect of a colon cancer patient in the radiotherapy process, the clinical total effective rate of a subject is 70%; the comparative example is three-purpose, when the side effect of a colon cancer patient in the radiotherapy process is relieved, the clinical total effective rate of a subject is 60 percent; when the comparative example four is used for relieving the side effects of a colon cancer patient in the radiotherapy process, the clinical total effective rate of a subject is 70%; in the radiotherapy process of a blank group of colon cancer patients, the clinical total effective rate of a subject is 60%; therefore, when the fucoidin composite preparation is used for relieving the side effect of a colon cancer patient in the radiotherapy process, the clinical total effective rate of a subject can be obviously improved, and the incidence rate of symptoms such as abdominal pain, hematochezia, inflammatory reaction and the like of the patient in the radiotherapy process is relieved; and the fucoidin combined preparation obtained by the invention has obviously better effect on improving the clinical overall effective rate of a subject than the first comparative example, the second comparative example, the third comparative example and the fourth comparative example.

Typical case

Case 1, Dongqi, male, age 63, early stage of colon cancer, was subjected to surgical resection, and was subjected to defecation more than 4 times per day, with loose stools, bloody stools, abdominal pain, and physical weakness, and was first subjected to radiation therapy. During radiotherapy, the fucoidin composition preparation is taken 2 times a day, 2g each time, and is taken with warm water. After the medicine is taken for one month, the defecation frequency is gradually reduced to 1-2 times per day, the defecation hardness is increased, the phenomena of hematochezia and abdominal pain are avoided, the body has no hypodynamia condition, and the detection of interleukin-6 and TNF-alpha is normal.

In case 2, the patient is subjected to surgical partial excision in the middle stage of the colon cancer in the age of 51 years old and poplars, defecates are more than 5 times every day, the phenomenon of tenesmus, hematochezia and abdominal pain occur in the defecations, and the patient is subjected to radiotherapy for the first time. During radiotherapy, the fucoidin composition preparation is taken 2 times a day, 2g each time, and is taken with warm water. After the medicine is taken for one month, the defecation frequency is regular, the defecation hardness is increased after 2 times a day, the phenomena of hemafecia, stomachache and hypodynamia are avoided, and the detection of interleukin-6 and TNF-alpha is normal.

Case 3, wangzhi, male, age 53, early stage lung cancer, surgical resection, poor appetite, poor immunity, physical fatigue, and initial radiation therapy. During radiotherapy, the fucoidin composition preparation is taken 2 times a day, 2g each time, and is taken with warm water. After the oral liquid is taken for one month, the appetite is improved, the mental state is improved, and the body fatigue phenomenon is obviously improved; the detection of ghrelin, leptin, interleukin-6 and interleukin-17 were all normal values.

Case 4, beam, male, age 54, early stage lung cancer, surgical resection, poor appetite, poor mental status, physical fatigue, and initial radiation therapy. During radiotherapy, the fucoidin composition preparation is taken 2 times a day, 2g each time, and is taken with warm water. After the oral liquid is taken for one month, the appetite is improved, the mental state is improved, and the body fatigue phenomenon is obviously improved. The detection of ghrelin, leptin, interleukin-6 and interleukin-17 were all normal values.

Therefore, compared with the prior art, the invention has the beneficial effects that: the fucoidin in the fucoidin composite preparation has the functions of resisting inflammation, improving the immunity of the organism and improving the malnutrition condition, the turmeric has the anti-inflammatory function, the aronia serrulata fruit powder and the grape seed extract have the antioxidation function, and the lactobacillus casei and the bifidobacterium lactis have the effects of regulating the intestinal flora and improving the immunity; the functional raw materials such as fucoidin, turmeric, aronia fruit powder and grape seed extract are matched with lactobacillus casei and bifidobacterium lactis, the components are scientifically matched, supplement each other and mutually promote, and the nutritional status of a patient is improved by adjusting the levels of ghrelin and leptin in a body; the level of inflammatory factors such as interleukin-6, interleukin-17 and the like in vivo is obviously reduced, and the incidence of radiotherapy inflammation is obviously reduced; reducing the level of matrix metalloproteinase MMP-9 tumor-related indexes, and enhancing the treatment effect of radiotherapy and chemotherapy; the composition is used for preparing the medicine for relieving the side effects of tumor radiotherapy and chemotherapy, plays a role in attenuation and synergism, can effectively relieve the side effects of low immunity, gastrointestinal dysfunction, inappetence, hypodynamia and the like of tumor patients during radiotherapy and chemotherapy, is beneficial to the recovery of the tumor patients, and improves the life quality of the patients. The preparation method of the fucoidin composite preparation is simple, is convenient to operate, has no special requirements on equipment, and is beneficial to realizing industrialization; the preparation conditions are mild, and the effective components in the fucoidin, the turmeric, the aronia melanocarpa fruit powder, the grape seed extract, the lactobacillus casei and the bifidobacterium lactis can be fully reserved, so that the effect of the fucoidin composite preparation is ensured.

The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.

Claims

1. The fucoidin composite preparation is characterized by comprising the following raw materials in parts by weight:

40-80 parts of fucoidin, 4-16 parts of turmeric, 1-18 parts of aronia serrulata fruit powder, 1-18 parts of grape seed extract, 1-10 parts of lactobacillus casei and 1-10 parts of bifidobacterium lactis.

2. The fucoidan combined preparation according to claim 1, which comprises the following raw materials in parts by weight:

50-70 parts of fucoidin, 5-15 parts of turmeric, 5-15 parts of aronia serrulata fruit powder, 5-15 parts of grape seed extract, 1-5 parts of lactobacillus casei and 1-5 parts of bifidobacterium lactis.

3. The fucoidan combined preparation according to claim 2, which comprises the following raw materials in parts by weight:

60 parts of fucoidin, 10 parts of turmeric, 10 parts of aronia serrulata fruit powder, 10 parts of grape seed extract, 5 parts of lactobacillus casei and 5 parts of bifidobacterium lactis.

4. The fucoidan combination preparation according to any one of claims 1-3, wherein:

the purity of the fucoidin is not less than 80%, and the purity of the grape seed extract is not less than 80%.

5. The fucoidan combination preparation according to any one of claims 1-3, wherein:

the turmeric is prepared by sun-drying, baking and grinding turmeric, and the wild cherry fruit powder is prepared by sun-drying, baking and grinding wild cherry.

6. The fucoidan combination preparation according to any one of claims 1-3, wherein:

the number of the lactobacillus casei is not less than 1 × 10¹⁰CFU/g, the number of the bacteria of the bifidobacterium lactis is not less than 1 multiplied by 10¹⁰CFU/g。

7. A method for preparing the fucoidan combination preparation according to any one of claims 1-6, comprising the steps of:

mixing fucoidin, Curcuma rhizome, Prunus serrulata fruit powder, grape seed extract, Lactobacillus casei and Bifidobacterium lactis, stirring for 20-40min, packaging, and sealing to obtain fucoidin composition.

8. Use of a fucoidan combination preparation according to any one of claims 1-6, wherein:

the fucoidin composite preparation is applied to preparing the medicine for relieving the side effect of tumor radiotherapy and chemotherapy.

9. The use of the fucoidan combination preparation according to claim 8, wherein:

the content of the effective components of the medicine is 5-99%.

10. The use of the fucoidan combination preparation according to claim 8, wherein:

the dosage form of the medicine is tablets, granules, capsules, pills, syrup, suspension or paste.