WO2017152834A1 - 一种雪柳叶层孔菌及其在制备药物中的用途 - Google Patents

一种雪柳叶层孔菌及其在制备药物中的用途 Download PDF

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WO2017152834A1
WO2017152834A1 PCT/CN2017/075919 CN2017075919W WO2017152834A1 WO 2017152834 A1 WO2017152834 A1 WO 2017152834A1 CN 2017075919 W CN2017075919 W CN 2017075919W WO 2017152834 A1 WO2017152834 A1 WO 2017152834A1
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cancer
tumor
grams
glabrata
fungus
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王大健
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王大健
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/14Fungi; Culture media therefor
    • C12N1/145Fungal isolates
    • CCHEMISTRY; METALLURGY
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    • C12RINDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00Microorganisms ; Processes using microorganisms
    • C12R2001/645Fungi ; Processes using fungi
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L31/00Edible extracts or preparations of fungi; Preparation or treatment thereof
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23FCOFFEE; TEA; THEIR SUBSTITUTES; MANUFACTURE, PREPARATION, OR INFUSION THEREOF
    • A23F3/00Tea; Tea substitutes; Preparations thereof
    • A23F3/34Tea substitutes, e.g. matè; Extracts or infusions thereof
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L2/00Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105Plant extracts, their artificial duplicates or their derivatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06Fungi, e.g. yeasts
    • A61K36/07Basidiomycota, e.g. Cryptococcus
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/14Fungi; Culture media therefor
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the invention relates to the technical field of microorganisms, in particular to a snow stalk of Schistosoma japonicum and its use in preparing medicines.
  • the treatment methods for tumors include surgical treatment, radiation therapy, interventional therapy and drug therapy.
  • Surgical treatment has a good effect on early patients, but its treatment is expensive, and it is not effective for advanced patients. Some patients cannot be treated for physical reasons, such as severe heart and lung or liver and kidney dysfunction.
  • drugs for treating tumors most of them are expensive and have poor effects.
  • Some therapeutic drugs, with a large amount of drugs and various types, are not only ineffective, but also bring many side effects and have adverse consequences.
  • Surgical treatment is harmful to the body; radiotherapy has been widely criticized for its side effects of “killing one thousand, self-destruction of eight hundred”. After a course of treatment, the patient’s immunity has dropped rapidly, most of them are weak, weak, and the side effects are very It may become the last straw for crushing patients. Later, targeted drugs came into being, which can accurately guide cancer cells, thus greatly reducing the damage to the body.
  • Targeted therapy is to design a corresponding therapeutic drug at the molecular level against a well-defined carcinogenic site (which may be a protein molecule inside a tumor cell or a gene fragment). Specific selection of oncogenic sites to combine to cause tumor cell-specific death without affecting normal tissue cells surrounding the tumor.
  • Targeted drugs have strong side effects: rash, abdominal pain, diarrhea, cracking of hands and feet, nasal bleeding, fatigue, hair loss, gastrointestinal discomfort, etc., targeted drugs can only delay the disease and can not be cured.
  • the anti-tumor substances of fungi can be divided into two major categories, macromolecular substances and small molecular substances. Macromolecular substances are mainly polysaccharides and polysaccharides linked to proteins, and small molecules mainly have phenolic compounds. Polyketones, terpenoids, steroids, and the like.
  • Another object of the present invention is to provide a fungal extract which is obtained by extracting from the genus Aspergillus.
  • It is still another object of the present invention to provide a fungal composition comprising the above-mentioned fungus of the genus Aspergillus oryzae or the fungal extract described above.
  • the snowy sphaerocephala provided by the present invention whose Latin name is Phyltoporia fontanesiae, was deposited on January 27, 2016 at the General Microbiology Center (CGMCC) of the China Microbial Culture Collection Management Committee, and the preservation number is CGMCC No. 11905.
  • CGMCC General Microbiology Center
  • the P. glabrata can be used for preventing and/or treating tumors (including benign tumors and malignant tumors) and improving immunity, and has remarkable curative effect, low cost, safety and reliability, good tolerance, small side effects and quick effect. Good compliance.
  • the sequence of the IRS region of the rRNA gene of the Phytophthora serrata is SEQ ID NO: 1, as follows:
  • sequence of the rRNA gene D1D2 region of the P. glabrata is SEQ ID NO: 2, as follows:
  • the porphyra is a porous bacterium grown at the base of the sapling of the snow stalk, one year or perennial; the fruiting body is covered, the cork is; the cap is up to 3.6 cm long and the width is up to 5.9 cm, the base is The thickness can reach 0.6cm, the surface of the cap is covered with fluff, yellow-brown to dark brown, with concentric ring pattern and sharp edges; the surface of the orifice is light yellow-brown to yellow-brown, with refractive effect, obvious infertile edge; ⁇ 12/mm, thick wall, whole edge; hyphae single type, reproductive hyphae with simple separation, colorless to yellowish brown, slightly thicker Wall to thick wall, rare branches, loosely interlaced, width 1.9 ⁇ 3.7 ⁇ m, spore wide oval, 2.3 ⁇ 3.1 ⁇ 1.9 ⁇ 2.4 ⁇ m, smooth surface, light yellow, thick wall.
  • the Schistosoma japonicus contains 39-40% of soluble polysaccharide, 19-20% of crude protein, 6-7% of crude fat, 10-11% of crude fiber, and 3-11% of crude fiber. 1.5%.
  • the P. glabrata further comprises: 9 to 15% of water, 4 to 6% of ash, and 8 to 10% of other organic components.
  • the Chrysosporium sylvestris comprises: soluble polysaccharide 39.4%, crude protein 19.3%, crude fat 6.4%, crude fiber 10.3%, triterpene 1.1%, by weight percent.
  • the P. glabrata further comprises: moisture 9.8%, ash 5.3%, and other organic components 8.4%.
  • the Schistosoma japonicum of the present invention is a strain cultured on a PDA medium after the tissue was found and separated in Wendeng District, Weihai City, Shandong City in the autumn of 2015.
  • the fungal extract provided by the present invention is obtained by extracting the above-mentioned P. glabrata.
  • the fungal composition provided by the present invention comprises the above-mentioned fungus of the genus Aspergillus oryzae or the above-mentioned fungal extract.
  • the present invention provides the use of the P. glabrata, fungal extract or fungal composition for the preparation of a medicament, a health supplement, a food, a drink or a tea for preventing and/or treating a tumor or improving immunity.
  • the tumor comprises a male tumor, a gynecological tumor, a respiratory tumor, a digestive system tumor, a urinary system tumor, a dermatological tumor, a ENT tumor, a hematology tumor, a orthopedic tumor, a neurological tumor, and a general surgery tumor.
  • the tumor comprises breast cancer, intestinal cancer (including colon cancer and rectal cancer), lung cancer, gastric cancer, esophageal cancer, thyroid cancer, liver cancer, cervical cancer, bladder cancer, uterine cancer, renal cancer, lymphoma , brain cancer, prostate cancer, ovarian cancer, nasal cancer, blood cancer, tracheal cancer, bronchial cancer, laryngeal cancer, pancreatic cancer, gallbladder cancer and bone cancer and other parts of the body cancer.
  • intestinal cancer including colon cancer and rectal cancer
  • lung cancer gastric cancer, esophageal cancer, thyroid cancer, liver cancer, cervical cancer, bladder cancer, uterine cancer, renal cancer, lymphoma , brain cancer, prostate cancer, ovarian cancer, nasal cancer, blood cancer, tracheal cancer, bronchial cancer, laryngeal cancer, pancreatic cancer, gallbladder cancer and bone cancer and other parts of the body cancer.
  • the medicament is a tablet, a decoction, a capsule, a granule, an injection or a lyophilized powder.
  • the P. glabrata can be applied by drying, pulverizing, or further preparing into a dosage form such as a capsule.
  • the P. glabrata is subjected to extraction to obtain a fungal extract which is further prepared into an administrable dosage form together with a pharmaceutically acceptable excipient and then applied.
  • the fungal extracts including but not limited to, are prepared by the following methods:
  • the fungus extract is obtained by mixing Schizophyllum serrata with a suitable amount of solvent, then immersing and/or heating, and filtering to obtain an extract, which is concentrated and dried.
  • the solvent is water, methanol, ethanol or a mixture thereof.
  • the P. glabrata is dried or dried; the drying temperature is 40 to 90 °C.
  • the P. sylvestris is pulverized.
  • the comminution is to facilitate the dissolution of the active ingredient in the bacterium of the genus Aspergillus.
  • the invention relates to the snow fungus, fungus extract and fungal composition of the present invention, focusing on the regulation of the whole body state, and strengthening the body, thereby enhancing the immune function and disease resistance of the tumor patient.
  • the invention has the following characteristics:
  • the invention adopts the snow fungus leaf fungus homogenate as a medicine and food homologous material, which is safe to use and has no obvious toxic and side effects.
  • the invention has the functions of improving the immunity of the body, exerting the characteristics of clearing away heat and detoxifying, promoting blood circulation and removing blood stasis, softening and dispersing the knot, and nourishing the body, and inhibiting the growth of the tumor cells, improving the metabolic balance of the body, restoring physical fitness, and alleviating the suffering of the patient.
  • Supporting the main, supplementing the evil spirits, improving the body's righteousness, increasing the sensitivity and tolerance of chemotherapy drugs, prolonging the survival time, and improving the quality of life have a significant effect.
  • the invention has the three principles of "supporting, preventing and treating" the treatment of tumors by the genus Aspergillus.
  • the "three principles" are effective treatments for tumors that are based on the unique pharmaceutical ingredients of the genus Schistosoma japonicum and combined with the pathological features of the tumor.
  • the Phyllostachys pubescens (Latin name Phylloporia fontanesiae) of the present invention is a fungus of the genus Basidiomycetes. Snowy Phytophthora is a new species, and there is no data to introduce its application value.
  • the Schistosoma japonicum of the invention has a wide range of pharmacological effects, such as anti-tumor effect, liver and detoxification, inhibition of cancer cells, and improvement of human immunity.
  • Chemical composition analysis showed that the soluble polysaccharide of the genus P. glabrata was 39-40%, the crude protein was 19-20%, the crude fat was 6-7%, the crude fiber was 10-11%, and the triterpene was 1 ⁇ . 1.5%, moisture is 9-15%, ash is 4-6%, and other organic components are 8-10%.
  • soluble polysaccharide is 39.4%
  • crude protein is 19.3%
  • crude fat is 6.4%
  • moisture is 9.8%
  • crude fiber was 10.3%
  • total triterpene was 1.1%
  • ash was 5.3%
  • other organic components were 8.4%.
  • the instruments used for the measurement include:
  • Soxhlet fat extractor model: YLA-2000
  • soluble polysaccharides and triterpenoids have a clear anti-cancer effect
  • the fungus has a large amount of soluble polysaccharides and triterpenoids, so it has immunomodulation, anti-tumor, anti-aging, blood circulation, anticoagulation, It protects the liver and other effects, and indirectly inhibits the growth of tumor cells or induces apoptosis of tumor cells by enhancing the body's immunity, effectively inhibiting tumor growth and exhibiting certain anti-tumor effects.
  • the method for the treatment of advanced malignant tumors of the present invention is as follows: the adult is orally administered three times a day, each time corresponding to 5 to 500 grams of the genus P. glabrata of the present invention, It can also be combined with other drugs, one course per month; or in the form of tea, or combined with other drugs, one course per month.
  • the invention is based on the understanding and treatment principle of traditional Chinese medicine for advanced malignant tumors, and is found by reference to modern drug research findings.
  • the snow willow fungus, fungal extract and fungal composition of the invention can enhance the phagocytic capacity of macrophages, regulate the immunity of the body, and improve the appetite by clearing away heat and detoxifying, dissipating phlegm, dispelling qi, nourishing the body, and atrophizing tumor capillaries. Enhance physical energy to inhibit tumor cell growth, improve symptoms, reduce patient suffering, and improve the quality of life of patients.
  • the treatment group of the present invention always has advanced tumor treatment.
  • the efficiency was 94.3%, and the total effective rate of the control group for advanced tumor treatment was 67.8%.
  • the total effective rate of the treatment group was significantly higher than that of the control group.
  • the invention can be prepared by decoction according to a conventional method, or can be processed into a traditional Chinese medicine pill and a traditional Chinese medicine granule by a conventional method, and can also be made into tablets, capsules and granules according to the daily dosage of the Chinese herbal medicine. Others, such as pieces, powder, powder, etc.
  • the present invention has been clinically applied, and generally the patient takes 5 to 10 days to take effect, and the slow 15 to 20 days is effective, the symptoms are improved, and the pain is relieved.
  • One month is a course of treatment. After 1 to 8 courses of treatment, it can have obvious effect or recovery. It is not easy to relapse after rehabilitation. It can also achieve therapeutic purposes for patients with advanced disease or patients who are not suitable for surgery, radiotherapy and chemotherapy, and postoperative recurrence and metastasis. .
  • the snow fungus body After harvesting, the snow fungus body is washed and cleaned, dried in the shade, or placed in a baking room for drying. The temperature is controlled at 55-85 ° C, and the water content of the fungus of the snow willow layer is about 10%. Store in a cool dry place or in the refrigerator. Then smash the snow willow layer to more than 80 mesh, directly take or about 1000 grams of water per 20 grams of snow willow layer bacteria is appropriate, can be added or subtracted, soaking for 2 to 8 hours before boiling, preferably after boiling It is advisable to cook for 25 to 30 minutes on a warm fire;
  • the snow willow layer is selected, washed, placed in an extractor, and added with 4 to 10 times the volume of the fungus of the snow willow layer.
  • the extraction temperature is 30-100 ° C
  • the extraction time is 1 to 10 hours
  • the filtration is performed. Obtaining the filtrate; repeatedly extracting 1 to 4 times, and combining the filtrates obtained each time to obtain a crude extract;
  • the crude extract is concentrated under reduced pressure on a concentrated solution of Chinese medicine, and the pressure under reduced pressure is -0.06 to -0.08 MPa, the evaporation temperature is 80 to 60 ° C, and the mixture is concentrated under reduced pressure to an extract having a relative density of 1.35 to 1.40.
  • the paste should be controlled at 50 ° C);
  • the extract and the auxiliary material are mixed in a mixing granulator, mixed with 65% to 75% of ethanol as a wetting agent, and stirred to form a soft material, which is granulated by a 14-mesh sieve to obtain wet granules.
  • the wet granules are sent to a hot air circulating drying oven for drying, the drying temperature is 60 ° C to 90 ° C, and the drying time is about 6 to 8 hours (flip every 2 hours).
  • the dry granules are granulated by a granulator with an 8-mesh sieve, and the granules after granulation are granulated in a oscillating sieve, and the number of sieves is 10 mesh and 80 mesh, respectively, to obtain dried granules of the genus P. glabrata (detecting moisture, Particle size, solubility and content);
  • the granules that have passed the inspection are packed in a granule automatic packaging machine, and the loading amount (20 g per bag) is different by ⁇ 4.5%.
  • Zhang male, 32 years old, liver cancer, recurrence after surgery, and 7 interventional treatments, multiple intrahepatic and spread to the lungs, the largest tumor more than 10cm, the hospital gave up treatment. Take 25 grams of porch, and follow the method of drying, pulverizing, soaking and boiling. After 8 months, the tumor shrinks to about 3.5cm. One year later, Mrs. Zhang's wife gave 3.9 kilograms of boy, mother and child health. . Zhang has a significant change in symptoms Good, chest pain, can be engaged in light physical labor.
  • the weight ratio is: 30 grams of Astragalus, 20 grams of Radix Pseudostellariae, 15 grams of Polygonatum, 12 grams of Atractylodes, 10 grams of alfalfa, 20 grams of raw land, 20 grams of Ophiopogon, 15 grams of aspartame 18 grams of Eclipta prostrata, 15 grams of Ligustrum lucidum, 30 grams of Hedyotis diffusa, 30 grams of Scutellaria barbata, 30 grams of dandelion, 15 grams of small medlar, 5 grams of licorice. Shuijianbi, 1 day, 2 times a day. After 8 months, the body's various indicators are normal, no different
  • the weight ratio is: 20 grams of Radix Pseudostellariae, 30 grams of Astragalus, 10 grams of Atractylodes, 12 grams of Astragalus 6 grams of dried tangerine peel, 12 grams of Huangjing, 30 grams of spatholobus, 15 grams of white peony, 10 grams of epimedium, 12 grams of rehmannia, 15 grams of malt, 15 grams of Hedyotis diffusa. Shuijianbi, 1 day, 2 times a day. After 6 months, the patient's life is as usual, and he can walk on his own without special discomfort. Occasionally, the Chinese medicine is conditioned to consolidate the curative effect and prevent recurrence.
  • CT scan of the chest the upper lobe of the two lungs with the left upper mediastinum, bilateral oblique pleura, multiple thoracic ribs, thoracic vertebrae and right scapula metastasis, multiple hilar lymph nodes in the hilar and mediastinum; bilateral pleural compression Invasion of a small amount of effusion on both sides, left upper lung small cell lung cancer multiple metastasis.
  • the water After taking 25 grams of porch, the water is about 1000 ml, and it is taken daily after drying, pulverizing, soaking and boiling. The condition is gradually reduced. After one year, there is no solid tumor by CT scan, and various indexes are normal. Engage in simple labor activities.
  • the spirit has improved, the appetite has increased, and the body weight has increased a lot.
  • the symptoms have basically disappeared.
  • the tumor in the liver disappeared, the condition was stable, the spirit was good, and the skin was rosy.
  • the condition of the patient was basically stabilized.

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Abstract

提供了一株雪柳叶层孔菌(Phylloporia fontanesiae),其于2016年1月27日保藏于中国微生物菌种保藏管理委员会普通微生物中心,保藏编号为:CGMCC No.11905。还提供了该雪柳叶层孔菌在制备预防和/或治疗肿瘤或者提高免疫力的药物、保健品、食品、饮品或者茶中的用途。

Description

一种雪柳叶层孔菌及其在制备药物中的用途 技术领域
本发明涉及微生物技术领域,具体涉及一种雪柳叶层孔菌及其在制备药物中的用途。
背景技术
目前,对于肿瘤的治疗方法有:手术治疗、放射治疗、介入治疗和药物治疗等。其中手术治疗对早期患者有很好的疗效,但其治疗费用昂贵,且对晚期患者治疗效果不佳,还有一些患者因身体原因不能进行手术治疗,如患者有严重心肺或肝肾功能不全。另外治疗肿瘤的药物虽然种类不少,但大都价格昂贵且效果不佳,一些治疗药物,用药量大、种类多,不仅效果不好,而且还会带来许多副作用,产生不良后果。
手术治疗对身体伤害较大;放射治疗一直因其“杀敌一千,自损八百”的副作用而广受诟病,一个疗程下来,病人免疫力急速下降,大多孱弱不堪,身体虚弱,副作用很可能会成为压垮患者的最后一根稻草。后来靶向药物应运而生,能精确制导癌细胞,因此大大减少了对身体的损伤。靶向治疗,是在分子水平上,针对已经明确的致癌位点(该位点可以是肿瘤细胞内部的一个蛋白分子,也可以是一个基因片段),来设计相应的治疗药物,药物进入体内会特异地选择致癌位点来相结合发生作用,使肿瘤细胞特异性死亡,而不会波及肿瘤周围的正常组织细胞。靶向药有很强的副作用:皮疹、腹痛腹泻、手脚疼痛开裂、鼻腔出血、疲倦、掉发、肠胃不适等,靶向药只能延缓病情且不能治愈。
我国大型真菌的药用历史悠久,《神农本草经》和《本草纲目》均记载了真菌的药用价值,其中灵芝(Ganderma lucidum)、茯苓(Poria cocos)和猪苓(Grifola umbellata)等被用于癌症的治疗。抗癌真菌的现代文献始于1903年,对真菌抗肿瘤作用的大规模研究始于二十世纪60年代,现已发现约650种担子菌具有抗肿瘤活性。真菌的抗肿瘤物可分为两大类,大分子物质和小分子物质,大分子物质主要是多糖和与蛋白相连的多糖,小分子主要有酚类化合物、 聚酮类化合物、萜类化合物和甾体等。
人们对于疗效好、安全性高的用于治疗肿瘤或提高免疫力的药物仍存在需求。
发明内容
针对现有技术的不足和人们日益增长的健康需求,本发明的一个目的是提供一种新的雪柳叶层孔菌。
本发明的另一目的是提供一种真菌提取物,其是以雪柳叶层孔菌为原料提取得到。
本发明的又一目的是提供一种真菌组合物,其含有上述雪柳叶层孔菌或者上述的真菌提取物。
本发明的又一目的是提供上述的雪柳叶层孔菌、真菌提取物或者真菌组合物在制备预防和/或治疗肿瘤或者提高免疫力的药物、保健品、食品、饮品或者茶中的用途。
本发明提供的雪柳叶层孔菌,其拉丁名为Phylloporia fontanesiae,于2016年1月27日保藏于中国微生物菌种保藏管理委员会普通微生物中心(CGMCC),保藏编号为:CGMCC No.11905。
所述雪柳叶层孔菌可以用于预防和/或治疗肿瘤(包括良性肿瘤和恶性肿瘤)和提高免疫力,并且疗效显著、成本低廉、安全可靠、耐受性好、毒副作用小、见效快、顺应性好。
优选地,所述雪柳叶层孔菌的rRNA基因ITS区序列(包括18S rRNA片段,ITS1、5.8S rRNA、ITS2的全序列及28S区序列片段)为SEQ ID NO:1,如下所示:
Figure PCTCN2017075919-appb-000001
Figure PCTCN2017075919-appb-000002
进一步优选地,所述雪柳叶层孔菌的rRNA基因D1D2区序列(包括28S rRNAD1-D2序列片段)为SEQ ID NO:2,如下所示:
Figure PCTCN2017075919-appb-000003
进一步优选地,所述雪柳叶层孔菌为生长于雪柳树干基部的多孔菌,一年或多年生;子实体盖型,木栓质;菌盖长可达3.6cm,宽可达5.9cm,基部厚可达0.6cm,菌盖表面被绒毛,黄褐色到深褐色,具有同心环纹,边缘锐;孔口表面浅黄褐色到黄褐色,有折光效应,不育边缘明显;孔口圆形,10~12个/mm,厚壁,全缘;菌丝单系型,生殖菌丝具简单分隔,无色到黄褐色,稍厚 壁到厚壁,少见分枝,疏松交织排列,宽1.9~3.7μm,孢子宽椭圆形,2.3~3.1×1.9~2.4μm,表面光滑,浅黄色,厚壁。
优选地,以重量百分比含量计,所述雪柳叶层孔菌包含:可溶性多糖39~40%、粗蛋白19~20%、粗脂肪6~7%、粗纤维10~11%、三萜1~1.5%。此外,所述雪柳叶层孔菌还包含:水分9~15%、灰分4~6%、其他有机组分8~10%。
更优选地,以重量百分比含量计,所述雪柳叶层孔菌包含:可溶性多糖39.4%、粗蛋白19.3%,粗脂肪6.4%,粗纤维10.3%,三萜1.1%。此外,所述雪柳叶层孔菌还包含:水分9.8%、灰分5.3%、其他有机组分8.4%。
本发明的雪柳叶层孔菌是于2015年秋在山东省威海市文登区发现并分离组织后在PDA培养基上培养得到的菌种。
本发明提供的真菌提取物,是以上述雪柳叶层孔菌为原料提取得到。
本发明提供的真菌组合物,含有上述雪柳叶层孔菌或者上述真菌提取物。
本发明提供所述雪柳叶层孔菌、真菌提取物或者真菌组合物在制备预防和/或治疗肿瘤或者提高免疫力的药物、保健品、食品、饮品或者茶中的用途。
优选地,所述肿瘤包括男科肿瘤、妇科肿瘤、呼吸系统肿瘤、消化系统肿瘤、泌尿系统肿瘤、皮肤科肿瘤、五官科肿瘤、血液科肿瘤、骨科肿瘤、神经科肿瘤和普外科肿瘤。
更优选且具体地,所述肿瘤包括乳腺癌、肠癌(包括结肠癌和直肠癌)、肺癌、胃癌、食道癌、甲状腺癌、肝癌、宫颈癌、膀胱癌、子宫癌、肾癌、淋巴癌、脑癌、前列腺癌、卵巢癌、鼻癌、血癌、气管癌、支气管癌、喉癌、胰腺癌、胆囊癌和骨癌等全身各部位癌症。
优选地,所述药物为片剂、汤剂、胶囊剂、颗粒剂、注射液或冻干粉针剂。
本领域技术人员可以理解,所述雪柳叶层孔菌可以将原料干燥、粉碎后直接施用或者进一步制备成剂型例如胶囊剂等施用。
优选地,将所述雪柳叶层孔菌进行提取,得到真菌提取物,该真菌提取物再进一步与药学上可以接受的辅料一起制备成可施用的剂型,然后施用。
所述真菌提取物,包括但不限于通过以下方法制备:
将雪柳叶层孔菌和适量水混合,然后浸泡和/或加热,过滤,非必需的浓 缩,即得真菌提取物;或者
将雪柳叶层孔菌和适量溶剂混合,然后浸泡和/或加热,过滤,得到提取液,将该提取液浓缩、干燥,即得真菌提取物。
优选地,所述溶剂为水、甲醇、乙醇或其混合物。
优选地,所述雪柳叶层孔菌是经过阴干或干燥的;干燥温度为40~90℃。
优选地,所述雪柳叶层孔菌是经过粉碎的。
本领域技术人员可以理解,粉碎是为了使得雪柳叶层孔菌中的活性成分更加容易地溶出。
本发明雪柳叶层孔菌、真菌提取物和真菌组合物,着眼于全身状态的调节,扶正固本,可以增强肿瘤患者机体的免疫功能和抗病能力。本发明与单纯使用西医化疗、放疗治疗相比,具有以下特点:
1、本发明选用所述雪柳叶层孔菌为药食同源材料,使用安全,无明显毒副作用。
2、本发明具有提高机体免疫力的作用,发挥清热解毒、活血化瘀、软坚散结、益气养身的特点,在抑制肿瘤细胞生长、改善机体代谢平衡、恢复体能、减轻患者痛苦,以扶正为主,祛邪为辅,提升机体正气,增加化疗药物的敏感性和耐受性,延长生存时间,改善生活质量上作用显著。
本发明雪柳叶层孔菌治疗肿瘤具有“扶、防、治”的三原则。第一,扶正气:扶患者的正气,提高患者的免疫力,修复受损的免疫缺陷。第二,防复转:防止复发转移,防止并发症的发生。第三,治病源:防止肿瘤细胞繁殖,杀灭肿瘤细胞。“三原则”是利用雪柳叶层孔菌的独特药物成分,结合肿瘤病理特点而总结出的行之有效的肿瘤治疗方法。
保藏说明:W-001,分类命名:雪柳叶层孔菌(Phylloporia fontanesiae)。保藏单位:中国微生物菌种保藏管理委员会普通微生物中心。保藏地址:北京是朝阳区北辰西路1号院3号中国科学院微生物研究所。保藏编号为:CGMCC No.11905。保藏日期:2016年1月27日。
具体实施方式
本发明的雪柳叶层孔菌(拉丁名Phylloporia fontanesiae),是担子菌纲多孔菌科的一种真菌。雪柳叶层孔菌为新种类,以前无资料介绍其应用价值。
本发明的雪柳叶层孔菌具有广泛的药理作用,如抗肿瘤作用、保肝解毒作用、抑制癌细胞、提高人体免疫力等作用。化学成分分析显示,本发明雪柳叶层孔菌的可溶性多糖为39~40%、粗蛋白为19~20%、粗脂肪为6~7%、粗纤维为10~11%、三萜为1~1.5%、水分为9~15%、灰分为4~6%、其他有机组分为8~10%,特别地,可溶性多糖为39.4%、粗蛋白为19.3%、粗脂肪为6.4%、水分为9.8%、粗纤维为10.3%、总三萜为1.1%、灰分为5.3%,其他有机组分为8.4%。
其中,测定使用的仪器包括:
能量色散X射线能谱仪;型号:JSM-7500F
紫外光谱仪;型号:TU-1901
凯氏定氮仪;型号:K9840
索氏脂肪提取器;型号:YLA-2000
生物显微镜;型号:上海XSP-8CA
其中,可溶性多糖和三萜类具有明确的抗癌作用,雪柳叶层孔菌含有大量的可溶性多糖和三萜类成分,故具有免疫调节、抗肿瘤,抗衰老、活血化淤、抗凝血、护肝等功效,并且通过增强机体免疫力间接抑制肿瘤细胞成长或者诱导肿瘤细胞凋亡,有效的抑制肿瘤生长,呈现一定的抗肿瘤作用。
本发明雪柳叶层孔菌、真菌提取物和真菌组合物用于治疗中晚期恶性肿瘤的使用方法为:成人每日口服三次,每次相当于本发明的雪柳叶层孔菌5~500克,也可与其他药物组合使用,每个月为一个疗程;或以茶水形式饮用,也可与其他药物组合使用,每个月为一个疗程。
本发明是基于中医药对中晚期恶性肿瘤的认识和治疗原则,参照现代药物研究发现,经实践而成。本发明雪柳叶层孔菌、真菌提取物和真菌组合物通过清热解毒、化痰散结、益气养身、萎缩肿瘤毛细血管的作用,增强巨噬细胞吞噬能力,调节机体免疫力,改善食欲,增强体能从而起到抑制肿瘤细胞生长,改善症状,减轻患者痛苦,提高患者生活质量的作用。
经临床对比发现:施用本发明雪柳叶层孔菌、真菌提取物和真菌组合物治疗一个疗程后,与对照组(施用化疗和放疗)相比,本发明的治疗组的中晚期肿瘤治疗总有效率为94.3%,对照组对中晚期肿瘤治疗的总有效率为67.8%,治疗组的总有效率明显高于对照组。
本发明按照组分配置好后,可以按照常规方法煎制成汤药服用,也可以用常规方法加工制作成中药丸药、中药冲剂服用,还可以根据中草药的日用剂量制成片剂、胶囊、颗粒、饮片、粉末等其他可服用的成品方式。
以抗肿瘤提高免疫力为例,本发明雪柳叶层孔菌经过临床应用,一般患者用药5~10天见效,慢的15~20天见效,症状改善,疼痛减轻。一个月为一疗程,用药1~8个疗程即可有明显效果或康复,康复后不易复发,另对中晚期患者或不宜手术、放化疗的患者以及术后复发转移者,也可达到治疗目的。
实施例
本发明内容不限于实施例所列举,本领域普通技术人员通过阅读本发明说明书而对本发明技术方案采取的任何等效的变换,均为本发明的权利要求所涵盖。
实施例1
采收后的雪柳叶层孔菌实体经过洗涤和清理后,阴干,或置于烤房内烘干,温度控制在55~85℃,烘至雪柳叶层孔菌含水量10%左右,存放于阴凉干燥处或冰箱保鲜。然后将雪柳叶层孔菌粉碎至80目以上,直接服用或者每20克雪柳叶层孔菌配约1000毫升水为宜,可酌量加减,熬煮前浸泡2~8小时为佳,沸腾后温火煮25~30分钟为宜;以饮茶形式热服。
实施例2
将雪柳叶层孔菌挑选,洗净,置于提取器中,加入4~10倍雪柳叶层孔菌体积的水进行提取,提取温度为30~100℃,提取时间为1~10小时,过滤得到滤液;反复提取1~4次,合并每次过滤的滤液得到粗提取液;
将粗提液在中药浓缩锅上进行减压浓缩,减压浓缩的压力为-0.06~-0.08MPa,蒸发温度为80~60℃,减压浓缩至相对密度为1.35~1.40的浸膏(浸膏要控制在50℃测);
将浸膏与辅料放入混合制粒机混合,以65%~75%的乙醇为湿润剂混合,搅拌制成软材以14目筛网制粒即得湿颗粒。
将湿颗粒送入热风循环干燥箱干燥,干燥温度60℃~90℃,干燥时间约6~8小时(每2小时翻动一次)。
将干颗粒用整粒机以8目筛整粒,整粒后的颗粒于振荡筛内选粒,筛网数目分别为10目和80目即得到雪柳叶层孔菌的干燥颗粒(检测水分,粒度,溶化性及含量);
检验合格的颗粒用颗粒自动包装机分装,装量(20克每袋),装量差异±4.5%。
实施例3
称取烘干的雪柳叶层孔菌20g,按下列方法制备:
a)第一次加水4~15倍量,煎煮1~8小时,第二次加水10倍量,煎煮2小时,合并药液,药液滤过,取滤液,浓缩至相对密度为1.10~1.15(60℃)时,加入乙醇使含醇量达到30%~80%,沉淀,静置24小时,吸取上清液,回收乙醇,得水提液;
b)浓缩,干燥,粉碎,得干膏粉;
c)将所得干膏粉与适量辅料充分混匀,以乙醇作粘合剂制粒,干燥,加入适量辅料混匀,制成片剂。
实施例4
称取烘干的雪柳叶层孔菌30g,按下列方法制备:
a)加50%~80%乙醇9倍量回流提取两次,第一次1~4小时,第二次1~5小时。合并药液,药液滤过,回收乙醇,得醇提液;
b)醇提后的药渣共同加水煎煮两次,第一次加水15倍量,煎煮2小时,第二次加水8倍量,煎煮2小时,合并药液,药液滤过,取滤液,浓缩至相对密度为1.10~1.15(50℃测)时,加入乙醇使含醇量达到40%~70%,沉淀,静置12~36小时,吸取上清液,回收乙醇,得水提液;
c)将所得醇提液和水提液合并,浓缩,干燥,粉碎,得干膏粉;
d)将所得干膏粉与适量辅料充分混匀,以乙醇液作黏合剂制粒,干燥, 加入适量辅料混匀,装入药用胶囊。
案例:
1、高某,女,43岁,因疼痛到医院检查确诊为乳腺癌,手术后做了4次化疗,复发扩散。取雪柳叶层孔菌20克,水1000毫升,按照干燥、粉碎、浸泡、煎煮后每日服用,5个月后检查各种指标基本正常,现肿瘤指标正常,可从事轻体力劳动。
2、乔某,男,65岁,农民,腹痛经医院检查发现肠癌,手术后两年内经过十余次的放化疗,后扩散,每天取雪柳叶层孔菌20克,水1500毫升,煎熬半小时后以茶水形式饮用,10个月后肿瘤指标消失,可从事轻体力农活。
3、毕某,女,34岁,因常咳嗽去医院检查,发现肺癌晚期,约鸡蛋大小,由于位置不好,已失去手术机会,每天取雪柳叶层孔菌约15克,水1000毫升,煎熬半小时后以茶水形式饮用。约6个月后肿瘤消失,已正常生活。
4、张某,男,67岁,南京某工厂退休职工,胃癌手术后,每日取雪柳叶层孔菌25克配1000毫升水熬做茶喝,常年饮用,并以清淡易消化食物为主,后移至海边城市居住,35年无复发。
5、李某,男,42岁,由于进食困难,声音嘶哑,医院检查确诊为食道癌,经过数次放疗效果不理想,无奈选择中医。每日取雪柳叶层孔菌50克,按照干燥、粉碎、浸泡、煎煮后服用,6个月后检查发现无实体肿瘤,指标正常,可正常工作。
6、洪某,女,39岁,由于感觉到心慌、消瘦、乏力,进而出现声音嘶哑,呼吸困难等压迫症状,经医院检查确诊为甲状腺癌。每日取雪柳叶层孔菌20克,按照干燥、粉碎、浸泡、煎煮后服用,两个月后身体感觉舒爽,生活质量明显提高,8个月后肿瘤消失。
7、张某,男,32岁,肝癌,经手术后复发,又进行了7次介入治疗,肝内多发并扩散到肺,最大的肿瘤超过10cm,医院放弃治疗。每日取雪柳叶层孔菌25克,按照干燥、粉碎、浸泡、煎煮后服用,8个月后肿瘤缩至3.5cm左右,一年后张某的夫人产下3.9公斤的男孩,母子健康。张某症状有明显改 善,胸背痛止,可从事轻体力劳动。
8、宫某,女,51岁,绝经后又出现阴道出血,妇科检查时发现子宫颈表面光滑或呈糜烂状、质硬、触之易出血,确诊为宫颈癌。三次化疗后无效,每日取雪柳叶层孔菌25克,按照干燥、粉碎、浸泡、煎煮后服用,一个月后症状减轻,6个月后无实体瘤,与常人无异。
9、刘某,男,57岁,由于有血尿两个月有余到医院检查确诊为膀胱癌,放射治疗效果不明显。每日取雪柳叶层孔菌20克,按照干燥、粉碎、浸泡、煎煮后服用,另配合其他药物,配重比为:生地、山药各30克,山萸12克,茯苓、猪苓紫草各30克,芦荟6克,小蓟、蒲黄炭各12克,半枝莲、白花舌草各30克。每日1剂,水煎服。一个月后血尿逐渐减少,7个月后无实体瘤,肿瘤指标正常,可从事轻体力工作。
10、张某,女,43岁,疼痛并子宫出血,经医院检查确诊为子宫癌,手术后扩散,经四次化疗后身体虚弱,每日取雪柳叶层孔菌20克,按照干燥、粉碎、浸泡、煎煮后服用,身体逐渐好转,7个月后无实体瘤,肿瘤指标正常。
11、车某,男,52岁,腰疼,尿里带血,有乏力、体重减轻、食欲不振等症状,经医院检查确诊为肾癌,手术后复发并肝、腹膜后淋巴结转移膀胱。每日取雪柳叶层孔菌22克,按照干燥、粉碎、浸泡、煎煮后服用。清淡饮食,10个月后检查无实体瘤,肿瘤指标正常。
12、李某,男,51岁,咳嗽、胸闷、气促、肺涨,到医院检查确诊为淋巴癌,化疗5个疗程,身体出现极度的虚弱状态及严重的化疗并发症,每日取雪柳叶层孔菌20克,按照干燥、粉碎、浸泡、煎煮后服用,一年后到医院检查各种指标正常,可从事轻体力劳动。
13、张某,男,37岁,因头痛、呕吐到医院检查,确诊为脑癌,化疗三次后效果不明显,每日取雪柳叶层孔菌20克,按照干燥、粉碎、浸泡、煎煮后服用,另配合其他药物,配重比为:柿蒂10克,丁香3克,生姜5克。水煎服,每日1剂,分2次服。10个月后检查无实体瘤,肿瘤指标正常。
14、赵某,男,63岁,因排尿困难、尿潴留、疼痛、血尿到医院检查确诊为前列腺癌,放疗两次后因身体状况较差改为中医治疗,每日取雪柳叶层孔 菌27克,按照干燥、粉碎、浸泡、煎煮后服用,8个月后检查无实体瘤,肿瘤指标正常。
15、张某,女,54岁,因腹痛检查发现卵巢癌且腹水严重,后做了5次化疗,每日取雪柳叶层孔菌22克,按照干燥、粉碎、浸泡、煎煮后服用,5个月后在同家医院检查,已基本趋近正常。
16、王某,男,58岁,因眼睛模糊看不清楚物体,到医院检查后发现鼻癌晚期,连续被两家三甲医院拒收,理由为无治疗意义,后每日取雪柳叶层孔菌23克,按照干燥、粉碎、浸泡、煎煮后服用,一个月后视力恢复正常,到曾拒收医院检查,发现已无肿瘤,医生惊讶,再次进行检查,确认已无实体肿瘤,可从事体力劳动,后间断服用,身体康复。
17、郑某,女,23岁,因头痛呕吐、牙龈肿胀,身体痛到医院检查确诊为血癌,四次化疗后身体虚弱,每日取雪柳叶层孔菌25克,按照干燥、粉碎、浸泡、煎煮后服用,另配合其他药物,配重比为:黄芪30克,太子参20克,黄精15克,白术12克,茯苓10克,生地20克,麦冬20克,天冬15克,旱莲草18克,女贞子15克,白花蛇舌草30克,半枝莲30克,蒲公英30克,小蓟15克,甘草5克。水煎服,每日1剂,日服2次。8个月后身体各种指标正常,与常人无异。
18、王某,男,62岁,咳嗽多年,经检查后发现喉癌,手术后化疗一次,后感觉化疗副作用大拒绝,每天取雪柳叶层孔菌15克熬水,每餐饭后饮用三分之一,连续喝半年,后偶尔喝,身体各种指标正常,11年无复发,生活无影响。
19、高某,男,43岁,消化不良,食欲不好,体重下降并伴随着疼痛,经医院检查确诊为胰腺癌,开腹后发现无法切除,给予关腹保守治疗,后每日取雪柳叶层孔菌25克,按照干燥、粉碎、浸泡、煎煮后服用,另配合其他药物,配重比为:柴胡15克,茵陈25克,鬼箭羽15克,金钱草30克,蛴螬12克,白英20克,生川军(后下)6克,枳实12克,厚朴15克,鼠妇10克,木香15克,白叩仁15克,焦三仙各15克,虎仗20克,八月扎20克.每日一剂,加水2000-2500ml,浸泡2小时,煎至200ml,滤渣取液,早晚各服 100ml。11个月后各种指标正常,生活无影响。
20、李某,女,66岁,由于上腹部持续性疼痛到医院检查确诊为胆囊癌,手术后化疗三次后扩散,后每日取雪柳叶层孔菌25克,按照干燥、粉碎、浸泡、煎煮后服用,10个月后患者各种指标正常,可从事简单的工作。
21、郑某,男,13岁,因股骨剧烈疼痛行动不便到医院就诊确诊为骨癌,家属被告知情况严重,来日无多,如做手术的话需切除整个下肢和骨盆,再进行化疗,预后不佳,且整个治疗过程风险极大,费用难料,患者也将承受巨大的痛苦。后每日取雪柳叶层孔菌25克,按照干燥、粉碎、浸泡、煎煮后服用,另配合其他药物,配重比为:太子参20克,黄芪30克,白术10克,茯苓12克,陈皮6克,黄精12克,鸡血藤30克,白芍15克,淫羊藿10克,熟地12克,麦芽15克,白花蛇舌草15克。水煎服,每日1剂,日服2次。6个月后患者生活一切如常,可自行行走,无特殊不适,偶尔中药调理,以巩固疗效,防止复发。
22、孙某,女,49岁,农民;因右侧乳房发现一肿块2个月而就诊。自述2个月前无意中发现右侧乳房有一小肿块,无疼痛,故没有在意。近来发现肿块不断增大,乳房皮肤肿胀,前来就诊,确诊为乳腺癌。后每天取雪柳叶层孔菌20克,水1000毫升,按照干燥、粉碎、浸泡、煎煮后每日当做茶水服用,6个月后检查各种指标基本正常,肿瘤指标正常。
23、李某,女,33岁,公司职工,体检发现肿瘤指标异常,进而检查确诊为乳腺癌,由于有家族遗传的乳腺癌历史,患者情绪非常的不稳定,化疗效果不佳,后每天取雪柳叶层孔菌25克,水800毫升左右,按照干燥、粉碎、浸泡、煎煮后每日服用,5个月后检查各种指标基本正常,可正常工作。
24、吴某,女,44岁,乳腺癌术后10个月,化疗结束后3个月,一年后复查时发现复发,后每天取雪柳叶层孔菌25克,水1000毫升左右,按照干燥、粉碎、浸泡、煎煮后每日服用,8个月后检查各种指标基本正常。
25、刘某,男,57岁,因持续出现血便被医院诊断为结肠癌,术后身体恢复得很好,本以为从此远离癌症折磨,一年后,右下腹出现间断性疼痛,精神状态较以前差,医院复查后确诊为结肠癌术后肝内转移。后每天取雪柳叶层 孔菌22克,水1000毫升左右,按照干燥、粉碎、浸泡、煎煮后每日服用,6个月后检查各种指标基本正常,B超复查显示肝内正常,未发现低回声团。
26、王某,男,45岁,经医院诊断为直肠癌,手术后经半年化疗身体康复,后长期未复查,两年后突感上腹部剧痛,休息也无法缓解,经医院超检查发现一巨大病灶,最后确诊为直肠癌肝转移。后每天取雪柳叶层孔菌25克,水1000毫升左右,按照干燥、粉碎、浸泡、煎煮后每日服用,病情逐渐减轻,体力增加,一年后检查各种指标基本正常,B超复查显示无实体瘤。
27、袁某,女,77岁,经医院确诊左上肺腺癌,两肺多发转移。后每天取雪柳叶层孔菌20克,水1000毫升左右,按照干燥、粉碎、浸泡、煎煮后每日服用,约10后,咳嗽闷气等症状明显减轻。3个月后症状完全消失,体能状态恢复正常,胸部CT显示原发灶和转移灶都有明显缩小。10个月后再次复查CT,肿瘤接近完全消失。
28、张某,男,70岁,咳嗽,淋雨受凉开始打喷嚏咳嗽,半声干咳持续6个多月。后咳嗽变得更频繁,明显加重,咳出血丝痰。到医院检查时右锁骨上摸到一个2公分的淋巴结,做锁骨上淋巴结穿刺,涂片发现转移癌细胞。再申请一个锁骨上淋巴结活检,病理报告显示转移性鳞癌,免疫组化提示来源于肺。后每天取雪柳叶层孔菌25克,水1000毫升左右,按照干燥、粉碎、浸泡、煎煮后每日服用,病情逐渐减轻,10个月后无实体瘤,各种指标正常。
29、费某,男,60岁,因胸闷咳嗽经医院确诊肺癌,上腹部CT平扫:肝脏多发转移瘤伴少量腹水。胸部CT平扫:两肺上叶占位伴左上纵膈、两侧斜裂胸膜、多发胸肋骨、胸椎及右侧肩胛骨转移,两侧肺门、纵膈内多发稍大淋巴结;两侧胸膜受侵伴两侧少量积液,左上肺小细胞肺癌多发转移。后每天取雪柳叶层孔菌25克,水1000毫升左右,按照干燥、粉碎、浸泡、煎煮后每日服用,病情逐渐减轻,一年后经CT扫描无实体瘤,各种指标正常,可从事简单的劳动活动。
30、尚某,女,53岁,厌食,有时呕吐,且呕吐次数渐增,上腹部疼痛等症状持续三个月去医院检查确诊为胃癌,自上述症状开始以来,体重减轻10kg。自觉餐后腹胀、疲惫无力及精神不振。有吸烟史,20支/天,但4年前 已戒烟。有饮酒嗜好,30g/天。后每天取雪柳叶层孔菌20克,水1000毫升左右,按照干燥、粉碎、浸泡、煎煮后每日餐后服用,一月后病情逐渐减轻,半年后无实体瘤,可从事简单家务。
31、廖某,女,78岁,因厌食疼痛到医院确诊为胃癌。因年事已高,求诊中医。刻诊:面黄肌瘦,脚软乏力,喜热食,寐差,大便2~3天一行,爪甲无华,舌红苔薄,脉缓。后每天取雪柳叶层孔菌25克,水1000毫升左右,按照干燥、粉碎、浸泡、煎煮后每日茶水形式服用,一月后病情逐渐减轻,半年后无实体瘤,各种指标正常。
32、谭某,男,23岁,在一家练歌房干服务生,几乎每晚11点多到烧烤摊位吃烤肉、喝啤酒。后连续感觉上腹突然出现疼痛不适症状,且越来越消瘦,经医院检查确诊为胃癌晚期。后每天取雪柳叶层孔菌24克,水1000毫升左右,按照干燥、粉碎、浸泡、煎煮后每日茶水形式服用,一月后病情逐渐减轻,半年后无实体瘤,各种指标正常。
33、王某,男,42岁,因其吞咽困难,去当地医院诊治。之后CT检查发现其食道的下段一3×4.5cm大小结节,食管镜下取活检病理为食道癌。故行放疗30次,治疗后吞咽困难缓解,复查病灶缩小至0.5cm大小。半年后复查时发现肺转移2处,大小约3×5×2cm、2×3cm结节,同时发现仍自觉腹胀不适,后每天取雪柳叶层孔菌25克,水1000毫升左右,按照干燥、粉碎、浸泡、煎煮后每日茶水形式服用,逐渐精神食欲好转,肿瘤逐渐缩小,9个月后无实体瘤,各种指标正常。
34、吕某,男,54岁,因吞咽困难,吞咽口水胸疼。到医院做食管镜检查之后,被确诊为食管中段有2.3cm恶性肿瘤。后每天取雪柳叶层孔菌20克,水1000毫升左右,按照干燥、粉碎、浸泡、煎煮后每日茶水形式服用,病情逐渐减轻,半年后检查无实体瘤,各种指标正常,可从事轻体力劳动。
35、孟某,男,65岁。患甲状腺癌晚期,做了甲状腺全切术及颈淋巴结清扫术,术后接受放疗,手术及放疗后遗症严重,严重影响患者正常生活,后复发,声音嘶哑,气音,颈部紧束感,肿胀,局部症状严重,颈肩麻木,头晕,头痛,患者生活质量严重下降,焦虑,痛苦不堪。后每天取雪柳叶层孔菌25 克,水1000毫升左右,按照干燥、粉碎、浸泡、煎煮后每日茶水形式服用,两周后患者复诊时声音已明显好转,开口说话已感轻松。精神状态明显好转,3个月后患者症状明显减轻,生活质量明显提高,复查血检基本正常。
36、肖某,女,52岁,直到2013年12月,经医院检查发现甲状腺右叶低回声结节,大小为1.2×1.2×1.2cm;入院甲状腺结节穿刺活检,病理报告显示甲状腺癌,经医院手术后复发,后每天取雪柳叶层孔菌20克,水1000毫升左右,按照干燥、粉碎、浸泡、煎煮后每日茶水形式服用,病情逐渐好转,半年后无实体瘤,各种指标正常。
37、李某,女,47岁,因嗓音突然沙哑,治疗未果后从新检查确诊为甲状腺癌,专家手术后,预计生存期两到三个月,由于术后身体状况不佳,拒绝进一步化疗复发,后每天取雪柳叶层孔菌20克,水1000毫升左右,按照干燥、粉碎、浸泡、煎煮后每日茶水形式服用,病情逐渐好转,三个月后检查无实体瘤,半年后检查各种指标正常,可从事做饭、洗衣等家务活动。
38、赵某,男,54岁,经医院检查肝胆上有1×1.5×1.2cm大小的恶性肿瘤,且属于低分化癌,手术后诸多反应:伤口疼痛、咳嗽、腹腔积液、症状性溃疡等,术后的一年半癌细胞右肝复发转移。如果再手术的话可能会让他身体极可能承受不了。后每天取雪柳叶层孔菌25克,水1000毫升左右,按照干燥、粉碎、浸泡、煎煮后每日茶水形式服用,病情逐渐好转,半年后检查各种指标正常,无实体瘤,与常人无异。
39、龚某,男,52岁,因肝区疼痛,乏力,发热等症状到医院检查,被诊断为原发性肝癌,肿块大小8.86×9.45cm,进行手术切除,术后症状未减,反而增重。出现食欲减退,腹胀不适,饭后加剧,乏力,消瘦,右上腹疼痛,呈刺痛。三个月后复查发现复发,后每天取雪柳叶层孔菌20克,水1000毫升左右,按照干燥、粉碎、浸泡、煎煮后每日茶水形式服用,病情逐渐好转,患者肝区疼痛减轻,精神有所好转,食欲增加,体重也增加了不少,各种症状基本上已经消失,经检查肝内的肿块消失,病情稳定,精神好,皮肤红润,通过复查患者的情况基本稳定。
40、苗某,女,40岁,半年前出现阴道出血,后来出现白带增多且伴恶 臭,经医院相关检查。妇科检查显示,患者宫颈重度糜烂,向外突出,伴少量渗血,子宫正常大小,宫旁组织软,无压痛,双附件无明显异常。盆腔磁共振扫描显示,子宫癌。宫颈活检显示“低分化鳞状细胞癌”。后每天取雪柳叶层孔菌20克,水1000毫升左右,按照干燥、粉碎、浸泡、煎煮后每日茶水形式服用,病情逐渐好转,半年后各种指标正常,无实体瘤,可正常工作。
41、刘某,女,35岁,19岁结婚,怀孕4次生育1个小孩,后因同房出血,量少,色红,白带多,黄色,有异味,患者自认为无异常,后阴道不规则出血并有右侧腰痛,到院检查发现宫颈菜花状肿瘤,转移子宫旁并侵犯右侧髂腰肌、髂骨、梨状肌、臀小肌,诊断宫颈癌晚期,已失去手术机会,治疗方案只能采用放疗+化疗,且治疗效果较差。后每天取雪柳叶层孔菌20克,水1000毫升左右,按照干燥、粉碎、浸泡、煎煮后每日茶水形式服用,10个月后检查已无实体瘤,各种指标正常。
42、王某,男,56岁,因尿血、排尿困难在当地医院体检被诊断为“膀胱癌”,并在医院进行手术切除及放化疗。术后一年时间,又见血尿,并伴有腰痛症状。随即家人将送到医院进行复查,诊断为“膀胱癌术后淋巴转移、盆腔转移”。后每天取雪柳叶层孔菌20克,水1000毫升左右,按照干燥、粉碎、浸泡、煎煮后每日茶水形式服用,两个月后,王某脚部浮肿好转,大便通畅,下肢麻木好转,可以独自出门遛弯,无明显不适。再次复查,腹主动脉及下腔周围所显示部分未见明显异常肿大淋巴结,双肾未见明显异常。血清指标均在正常范围之内。
43、费某,男,61岁。半年内反复出现血尿7-8次,每次总要持续3-4天才渐渐消失,经医院检查发现:在膀胱左侧壁靠近左侧输尿管膀胱开口处旁边,有一个直径约2cm的肿块,突向膀胱腔内。作病理检查,结果报告为膀胱癌。手术后复发,后每天取雪柳叶层孔菌25克,水1000毫升左右,按照干燥、粉碎、浸泡、煎煮后每日茶水形式服用,一个月后病情逐渐缓解,半年后无实体瘤,各种指标正常。
44、杨某,女,59岁。因阴道不规则流血伴下腹部胀痛40余天,经医院切片病理确认子宫内膜癌。因身体虚弱病人拒绝了手术,后每天取雪柳叶层孔 菌20克,水1000毫升左右,按照干燥、粉碎、浸泡、煎煮后每日茶水形式服用,一个月后病情逐渐缓解,半年后无实体瘤,各种指标正常。
45、罗某,女57岁,因阴道不规则出血到医院检查确诊为子宫内膜癌,后在医院化疗5次,放射治疗一周,三个月后因再次出血而住院,并发现周围组织有转移,又化疗三次效果不明显,下腹坠胀感且跳痛。后每天取雪柳叶层孔菌20克,水1000毫升左右,按照干燥、粉碎、浸泡、煎煮后每日茶水形式服用,一个月后病情逐渐缓解,半年后无实体瘤,各种指标正常。

Claims (10)

  1. 一种雪柳叶层孔菌,该菌拉丁名为Phylloporia fontanesiae,于2016年1月27日保藏于中国微生物菌种保藏管理委员会普通微生物中心,保藏编号为:CGMCC No.11905。
  2. 根据权利要求1所述的雪柳叶层孔菌,其特征在于,所述雪柳叶层孔菌的包括18S rRNA片段,ITS1、5.8S rRNA、ITS2的全序列及28S区序列片段的rRNA基因ITS区序列为SEQ ID NO:1。
  3. 根据权利要求1所述的雪柳叶层孔菌,其特征在于,所述雪柳叶层孔菌的包括28S rRNAD1-D2序列片段的rRNA基因D1D2区序列为SEQ ID NO:2。
  4. 根据权利要求1所述的雪柳叶层孔菌,其特征在于,所述雪柳叶层孔菌为生长于雪柳树干基部的多孔菌,一年或多年生;子实体盖型,木栓质;菌盖长可达3.6cm,宽可达5.9cm,基部厚可达0.6cm,菌盖表面被绒毛,黄褐色到深褐色,具有同心环纹,边缘锐;孔口表面浅黄褐色到黄褐色,有折光效应,不育边缘明显;孔口圆形,10~12个/mm,厚壁,全缘;菌丝单系型,生殖菌丝具简单分隔,无色到黄褐色,稍厚壁到厚壁,少见分枝,疏松交织排列,宽1.9~3.7μm,孢子宽椭圆形,2.3~3.1×1.9~2.4μm,表面光滑,浅黄色,厚壁。
  5. 根据权利要求1所述的雪柳叶层孔菌,其特征在于,以重量百分比含量计,所述雪柳叶层孔菌包含:可溶性多糖39~40%、粗蛋白19~20%、粗脂肪6~7%、粗纤维10~11%、三萜1~1.5%。
  6. 一种真菌提取物,其特征在于,所述真菌提取物是以雪柳叶层孔菌为原料提取得到。
  7. 一种真菌组合物,其特征在于,所述真菌组合物含有权利要求1~5任一项所述的雪柳叶层孔菌或者权利要求6所述的真菌提取物。
  8. 权利要求1~5中任一项所述的雪柳叶层孔菌、权利要求6所述的真菌提取物或者权利要求7所述的真菌组合物在制备预防和/或治疗肿瘤或者提高免疫力的药物、保健品、食品、饮品或者茶中的用途。
  9. 根据权利要求8所述的用途,其特征在于,所述肿瘤包括男科肿瘤、妇科肿瘤、呼吸系统肿瘤、消化系统肿瘤、泌尿系统肿瘤、皮肤科肿瘤、五官科肿瘤、血液科肿瘤、骨科肿瘤、神经科肿瘤和普外科肿瘤;优选地,所述肿瘤包括乳腺癌、肠癌、肺癌、胃癌、食道癌、甲状腺癌、肝癌、宫颈癌、膀胱癌、子宫癌、肾癌、淋巴癌、脑癌、前列腺癌、卵巢癌、鼻癌、血癌、气管癌、支气管癌、喉癌、胰腺癌、胆囊癌和骨癌。
  10. 根据权利要求8~9任一项所述的用途,其特征在于,所述药物为片剂、汤剂、胶囊剂、颗粒剂、注射液或冻干粉针剂。
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