CN100515465C - Gamboge preparation for treating various malignant tumors - Google Patents

Abstract

The present invention relates to Chinese medicine preparation, and is especially a kind of gamboge preparation for treating malignant tumors and its preparation process. The gamboge preparation is prepared with gamboge 25-35 weight portions, bletilla tuber 15-25 weight portions, natural indigo 40-60 weight portions, cape jasmine 20-30 weight portions, and blood clam shell 30-40 weight portions. The gamboge preparation has obvious curative effect on malignant tumors, less toxic side effect and no inhibition on blood picture.

Description

Treat the Gamboge preparation of multiple malignant tumor

Technical field

The present invention relates to a kind of Chinese medicine preparation, specifically, is a kind of Gamboge preparation for the treatment of multiple malignant tumor.

Background technology

Resina garciniae is a Chinese medicine simply, motherland's medical book record, and Resina garciniae has counteracting toxic substances, phagedenoma, and removing blood stasis eliminating stagnation etc. is attacked effect,

External treatment carbuncle, scrofula, stubborn dermatitis, malignant boil, overdose have saying of envelope larynx.The inquiry data at home and abroad is not seen the treatment report that is useful on cancer etc.

Summary of the invention

The object of the present invention is to provide a kind of Gamboge preparation of the multiple malignant tumor of treatment based on Resina garciniae.

For achieving the above object, the present invention adopts following technical scheme: it is made by the raw material of following composition by weight: Resina garciniae 25-35, Pseudobulbus Bletillae (Rhizoma Bletillae) 15-25, Indigo Naturalis 40-60, Fructus Gardeniae 20-30, Concha Arcae 30-40.

Its preparation technology is as follows:

A, Resina garciniae raw alcohol concentration contract extractum;

B, get Resina garciniae extractum, Rhizoma Bletillae powder, Indigo Naturalis powder, Fructus Gardeniae powder, Concha Arcae powder, add starch routinely method for preparing tablet thereof mix, the damping material, the oven dry of system granule, granulate adds 0.5% magnesium stearate, tabletting gets final product.

The inventor is from June, 1973, and, antiinflammatory anticancer to Resina garciniae carried out a series of research, and the scientific research through hardships decades has confirmed that the main anticancer effective component in the Resina garciniae is gamlogic acid, allogambogic acid, neogambogic acid.The inventor has not only broken through traditional usage that Resina garciniae cannot be taken orally to the research of Resina garciniae, and has received the special result of treatment cancer.Resina garciniae treatment cancer, its toxic and side effects is little than chemotherapeutics such as the 5-Fu of clinical use, camptothecine, cyclophosphamide, no hemogram inhibitory action.

Efficacy experiment

1, Resina garciniae antitumor action

Experiments such as nineteen eighty-two Lei Qiumo show that Resina garciniae is to mouse hydroperitoneum type hepatocarcinoma ECA, ARS, S ₁₈₀, S ₃₇, MA ₇₃₇, U ₁₄, ARA ₄, W ₂₅₆Inhibitory action is arranged, and suppression ratio is 35.6%～80.0%, the lethal effect that the human liver cancer cell BEL-7402 and the strain of HeLa cervical cancer cell of In vitro culture also had varying degree; The SMMC-7721 hepatoma cell strain is also had tangible lethal effect, and this lethal effect and cyclophosphamide are approximate, greater than 5-fluorouracil, less than amycin.The Cao Ji people in 1980 etc. once had obvious suppression and lethal effect to In vitro culture hepatoma cell strain SMMC-7721.Contrast experiment for index observes from cultured cell morphology damage, and Resina garciniae is eager to excel than the inhibitory action of amine salt, pretazettine in camptothecine, the lycorine.Liu Ruoyong etc. merge radiotherapy to Resina garciniae to be had potentiation, can improve mouse tumor MA ₇₃₇Radiocurable effect.Cheng Tingkai etc. can cause S by the electron microscopic observation Resina garciniae ₁₈₀Cell surface microvilli reduces, even disappears; Rough endoplasmic reticulum obviously reduces, and mitochondrion swells, gauffer, even breaks, and can make mice reticulum cell sarcoma ARA ₄Ascites cells mitosis and amitosis index significantly reduce.Radiocolloid ¹⁹⁸Gold does not have obvious enhancing or inhibition to the animal body immunologic function; It is synthetic that the isotope autoradiography points out this medicine to suppress ARS oncocyte DNA, influences the number of chemical composition of oncocyte, similar with alkylating agent, belongs to the cell cycle nonspecific drug.1984, usefulness flow cytometry (FCM) such as mound Xiang Huan in 1986 and precociously assemble the influence that the research of chromosome (PCC) method was divided a word with a hyphen at the end of a line to HeLa cell, Murine Ascitic Hepatoma Cells cycle also proves G ₂It is the main mechanism that suppresses that → M delays.

2, gamlogic acid antitumor action

Use flow cytometry (FCM) and precocious dyeing (PCC) method of assembling is observed the influence that gamlogic acid was divided a word with a hyphen at the end of a line to HeLa cell and Murine Ascitic Hepatoma Cells cycle, found that 1.8 μ g/ml pair cells have obviously kills and wounds, and cell death is more than 20%.Mouse hydroperitoneum type hepatocarcinoma is had same inhibitory action during with 15mg/kg dosage, effect suppress for gamlogic acid can cause the Hela cell cycle each the time phase cell number change, G phase, S phase and the minimizing of M phase cell.And G ₂The phase cell increases, and illustrates that medicine can suppress G ₂The phase cell was divided a word with a hyphen at the end of a line to the M phase; Dong became the gamlogic acid effect 24hr with 5 μ g/ml in 1988, can effectively kill hepatoma carcinoma cell, and its antitumaous effect and drug level and action time are proportionate; Yellow Yongchang is reported the gamlogic acid lumbar injection S ₁₈₀Ascitic type has the obvious suppression effect; But for avoiding the individual variation of tumor, select the not good mice transplantability net cell plastid sarcoma of energy for growth to carry out inhibition test, suppression ratio is respectively 32.9%, 38.1% and 40.1%, proves to have tumor-inhibiting action equally.During with H500 type scanning electron microscopic observation gamlogic acid intraperitoneal administration, the microvillus of ehrlich ascites cell is seen obvious minimizing or disappearance, mitochondrial swelling, and ultrastructure such as break; And ARA ₄Cell mitogen and amitosis index significantly reduce, thereby point out this medicine may belong to a kind of cytotoxic drug.

3, neogambogic acid antitumor action

Experiment shows that neogambogic acid has that anticancer spectrum is wide, the low characteristics of toxicity.With the gamlogic acid contrast, neogambogic acid is to mouse leukemia L ₁₂₁₀Inhibitory action more excellent, prolongs the highest life cycle and can reach 292%, and the highest of gamlogic acid reaches 119%.Research to the ehrlich carcinoma curative effect has also shown effectively strong dependency of new Resina garciniae, the increase that (ip) its trophophase prolongs with dosage in dosage 3.6mg/kg～7.0mg/kg scope increases, simultaneously administering mode with the next day, every 4 days or once heavy dose of administration ehrlich carcinoma all there is obvious curative effects, and than administration every day is excellent, for clinical application provides foundation.Neogambogic acid is to S simultaneously ₁₈₀, Lewis lung cancer, Las ₇₉₅Solid carcinomaes such as adenocarcinoma of lung all have better inhibitory action, and the effect of certain selectivity metastasis is arranged.Use micro ectrophotometry and scan method and studied neogambogic acid L ₁₂₁₀The influence in leukaemia's cycle, the result shows that neogambogic acid (10mg/kg) can make S phase cell reduce G ₁The phase cytosis new cell peak occurs at low passage place.The appearance of these low DNA content cells has illustrated that neogambogic acid can suppress G ₁The carrying out of～S phase cell; Also may be because this medicine has destroyed S phase cell.In addition, neogambogic acid (10mg/kg) is to L ₁₂₁₀The rna content of cell also has obvious attenuating effect.

4, other

Zhu in 1984 weeps to weigh to wait and once used 30% Resina garciniae tincture concentration at l0 ^-7During g/ml to SM ₄₄-RK ₇Growth inhibitory action is arranged, think that tentatively Resina garciniae has direct inhibitory action to herpesvirus I type.Nanchang City Medical House microbe research chamber is measured the Resina garciniae antibacterial effect and is thought that gram-positive bacterium is had antibacterial action, and the antibacterial action to bacillus is stronger especially.

5, staining cell morphological observation

Mouse inoculation cancerous cell (ECA, S ₁₈₀The ascitic type cell) after, with the treatment of gamlogic acid 5mg/kg amount, puts to death animal after continuous 7 days respectively, get the peritoneal exudate smear, establish normal control and cyclophosphamide (15mg/kg) positive control simultaneously.The matched group growth of cancer cells is vigorous, and RNA is abundant, and green one the Lip river uniform particles of first distributes, and cell is round bright-coloured, visible blue dark nuclear and thick red kernel, and division mostly is side plate shape, flower type mutually, divides the normal pseudopodium sample of phase endochylema projection also visible latter stage.Cyclophosphamide-a control group cancerous cell is similar to the normal control group, weakens but the cavity basophilia often appears in cancerous cell.The gamlogic acid experimental group does not find cancerous cell, sees a large amount of leukocyte.Mouse inoculation ECA cell, pneumoretroperitoneum administration in 6 days, morphocytology did not have much variations in 1,2 day, and after the administration in 3,4 days, cavity appears in visible cell, and the nuclear that has blurs, disappears or dissolving, and visible a large amount of leukocyte.

6, toxicity test

The ip in mice acute toxicity test, Resina garciniae LD ₅₀Be 33mg/kg (fiducial limit 26-40); Gamlogic acid LD ₅₀Be 6.2 ± 0.5mg/kg; Neogambogic acid LD ₅₀Be 22.0 ± 2mg/kg.If it is heavy dose of medication can cause rabbit, rat, white mice organ disease, obvious with liver, kidney, lung especially; Low dose of accumulation medication, though dosage with last identical, pathological changes is significantly slight, limit to.Effective dose acts on Canis familiaris L., and the heart, liver, renal function do not have significant change, and only when adding 10 times of usual amounts, the electrocardiogram of rabbit has of short duration T ripple to shorten and the T ripple is little falls, so point out Resina garciniae to be used safely in clinical by the grasp dosage range.

7, internal metabolism

³The gamlogic acid of H labelling was still kept high concentration in 24 hours in the tumor body, and excretion is low, to organs and tissues selective gather in the acting body distribute higher with liver spleen content.Other is S ₁₈₀The solid tumor autoradiography observation shows, is full of labeled drug at 5 ~ 7 hours in the hepatocellular endochylema, takes second place in the white pulp of spleen; A small amount of radioactive grain appears in the proximal convoluted tubule of 9 hours cardiac muscle fiber film places, kidney, and few in the lung; Radioactive grain after 24 hours in each organs and tissues does not increase.

8, clinical use

The Gamboge preparation that uses comprises injection, tablet, ointment, paste and tincture.1 month is a course of treatment, and each patient can be with 1 to a plurality of courses of treatment.Effectively generally about 2 weeks, after the most of patients medication, ordinary circumstance is improved, and shows as appetite and promotes case onset time, and abdominal distention alleviates, pain relief or disappearance, and the tumor body dwindles in various degree or metastasis is controlled; To some than lose late period surgical engine can the patient diminish by stages after, also obtained possibility of excision, prolonged band cancer life cycle and improved quality of life.Different sick kind of treatment selected different dosage form for use, as the solid tumor multiselect with injection and/or tablet, ointment; Can select tincture, ointment, injection for use to body surface cancer ulcer; Cervical erosion and all types of dermatosis can be selected paste or tincture for use; This medication effect and histological type, the focus form has certain association, such as preferable to the rodent ulcer short-term effect, ulcer type skin carcinoma curative effect is better than enclosed mass type skin carcinoma again, but can not prevent recurrence fully, and the case of recurrence once more medication also take effect this medicine and radiotherapy or chemotherapy and with sensitization in addition; Therapeutic Method contrasts such as its curative effect of paste treatment cervical erosion and electricity iron, burning hot, freezing, FUYANLING, silver nitrate, butyric acid anhydride, effective percentage is higher, and cure rate is placed in the middle, does not need special installation, on average adds medicine to and can cure for 3～7 times.Reports such as nineteen eighty-two Lei Qiumo are treated skin carcinoma, breast carcinoma, malignant lymphoma, soft tissue sarcoma, head and neck cancer etc. with Resina garciniae extract and are obtained short term effect preferably, and 125 routine total effective rates are 69.69%, and obvious effective rate is 21.6%; Also useful Gamboge paste part is coated with treatment cervical erosion 478 examples, and effective percentage is 95.82%, and average medication is promptly healed for 6～7 times; 1986 again in succession report with 5% Gamboge soft paste cooperate injection and or tablet in treatment 41 routine skin carcinomas, total effective rate is 71%, obvious effective rate is 41% (this medicine is once used in foreign-aid medical team by famous department of dermatologry expert Huang Chaoping professor, has obtained the curative effect of satisfaction); Lei Qiumo in 1986 etc. cooperate operation Comprehensive Treatment breast carcinoma 77 examples with Resina garciniae, total effective rate is 76.6%, obvious effective rate 19.5%, wherein the person maybe may strive for treating before operator is as art to there being the surgical condition, and tumor is dwindled, and diminishes by stages, for condition has been created in operation, present the necrosis in different degree change under the cutting-out specimen mirror, the carcinoma periphery is also seen obvious lymphocyte, plasma cell and monocyte infiltration, and the prompting Resina garciniae has certain inhibition and lethal effect to breast carcinoma.The clinical list of the Pan De of Shangrao tumour hospital is obtained better effects with Resina garciniae injection for treating malignant tumor; 1988 again to the case follow-up study more than the Resina garciniae treatment produce effects, find malignant tumor late 7 years not relapse and metastasis 4 examples are arranged, more than 10 years not relapse and metastasis 3 examples are arranged, have the treatment of minority recidivist reuse Resina garciniae still effective; 184 Dong of hospital of PLA become with the gamlogic acid injection directly to inject hepatocarcinoma lump place in addition, have obtained that cancer obviously dwindles, the curative effect of necrocytosis.Former director Li Zhizhu of the military region, Jiangxi Province medical clinic portion suffers from not differentiated squamous-cell carcinomas of root of the tongue portion, advises excision, and the cervical region cleaning is not accepted and only adds the Resina garciniae treatment one course of treatment through radiotherapy, does not recur in year surplus in the of 20 so far; Nanchang The Third Hospital's oncology and Hunan Province tumour hospital had once also obtained the effect that tumor is obviously dwindled with Resina garciniae injection action arteries and veins interventional therapy.Lei Qiumo etc. have carried out pathomorphism school work observation to the pathological biopsy and the specimens from pri of 43 routine malignant tumor, see that the different regression necrosis of degree appears in some cases cancer after the Resina garciniae treatment; The case cancerous cell complete obiteration of curing, and visible newborn tissue.In addition, observe immunologic function lymphocyte between 31 routine mammary gland cancerous protuberance peripheries and normal structure, plasma cell reaction, find to be height, each 9 example of moderate reaction, mild reaction 12 examples, reactionless 1 example.In addition, imitate special good with ointment or tincture treatment innominate toxic swelling, scytitis, ulcer skin ulcer pustule on the face.

Aspect the toxicity observation, to 108 routine patient's hemogram paired observations, have 30 examples to do the platelet inspection not have significant change, show that this medicine does not have obvious inhibition to bone marrow.Also have 41 examples to make routine urinalysis before and after treatment, 35 examples have been made hepatic and renal function, and 25 examples have been done the Electrocardioscopy contrast, and all Non Apparent Abnormality changes.There are 4 examples in 2～5 years, to be interrupted or use 3～5 year course of treatment of Resina garciniae continuously, harmless to function aspects such as nervous system and the heart, liver, kidneys, do not suppress bone marrow and damage function of immune system lymphocyte, plasma cell again, thus think a kind of relatively safety, and the cancer therapy drug that can link up for a long time and use.Main side reaction is intravenous injection consumption when excessive, and to the body constitution extreme difference, phenomenons such as a giddy of crossing property, perspiration, xerostomia, erythra can appear in the advanced carcinoma patient that nutrition is not good enough.But generally can both die away, indivedual reaction weight persons all have improvement after anti symptom treatment.Tablets has a few patients to produce slight abdominal pain diarrhea, but the carrying out of unlikely influence treatment.The intravenous injection overflow of drug fluid, instillation is overrun, and concentration is high slightly or the time is longer, can cause local swelling and pain; Even cause superficial phlebitis, its incidence rate is 9.6%, after take first transfusion, confirm to add the Resina garciniae fluid drip again outside the ne-leakage blood vessel, drip and give a small amount of Glucose Liquid flushing after finishing, the disease feelings can obviously alleviate and take a turn for the better.

The present invention becomes the Resina garciniae sheet with other Chinese herbal and crude drugs preparationses of Resina garciniae compatibility, is used for the multiple malignant tumor of clinical treatment, and clinical effectiveness is obvious and toxic and side effects is little, to hemogram unrestraint effect, is the Chinese medicine rarity of motherland simply that is worthy to be popularized.

The specific embodiment

Embodiment 1: it comprises the composition of following composition by weight: Resina garciniae 25, Pseudobulbus Bletillae (Rhizoma Bletillae) 15, Indigo Naturalis 40, Fructus Gardeniae 30, Concha Arcae 40.

Its preparation technology is as follows:

A, Resina garciniae raw alcohol concentration contract extractum;

B, get Resina garciniae extractum, Rhizoma Bletillae powder, Indigo Naturalis powder, Fructus Gardeniae powder, Concha Arcae powder, add starch and press method for preparing tablet thereof and mix, the damping material, the system granule is dried, and granulate adds 0.5% magnesium stearate, and tabletting gets final product.

Embodiment 2: it comprises the composition of following composition by weight: Resina garciniae 35, Pseudobulbus Bletillae (Rhizoma Bletillae) 25, Indigo Naturalis 60, Fructus Gardeniae 20, Concha Arcae 30.

Its preparation technology is as follows:

A, Resina garciniae raw alcohol concentration contract extractum;

B, get Resina garciniae extractum, Rhizoma Bletillae powder, Indigo Naturalis powder, Fructus Gardeniae powder, Concha Arcae powder, add starch and press method for preparing tablet thereof and mix, the damping material, the system granule is dried, and granulate adds 0.5% magnesium stearate, and tabletting gets final product.

Embodiment 3: it comprises the composition of following composition by weight: Resina garciniae 30, Pseudobulbus Bletillae (Rhizoma Bletillae) 20, Indigo Naturalis 50, Fructus Gardeniae 25, Concha Arcae 35.

Its preparation technology is as follows:

A, Resina garciniae raw alcohol concentration contract extractum;

B, get Resina garciniae extractum, Rhizoma Bletillae powder, Indigo Naturalis powder, Fructus Gardeniae powder, Concha Arcae powder, add starch and press method for preparing tablet thereof and mix, the damping material, the system granule is dried, and granulate adds 0.5% magnesium stearate, and tabletting gets final product.

Embodiment 4: it is made up of the composition of following composition by weight: Resina garciniae 27, Pseudobulbus Bletillae (Rhizoma Bletillae) 18, Indigo Naturalis 46, Fructus Gardeniae 28, Concha Arcae 32.

Its preparation technology is as follows:

A, Resina garciniae raw alcohol concentration contract extractum;

B, get Resina garciniae extractum, Rhizoma Bletillae powder, Indigo Naturalis powder, Fructus Gardeniae powder, Concha Arcae powder, add starch and press method for preparing tablet thereof and mix, the damping material, the system granule is dried, and granulate adds 0.5% magnesium stearate, and tabletting gets final product.

Embodiment 5: it comprises the composition of following composition by weight: Resina garciniae 33, Pseudobulbus Bletillae (Rhizoma Bletillae) 23, Indigo Naturalis 56, Fructus Gardeniae 23, Concha Arcae 36.

Its preparation technology is as follows:

A, Resina garciniae raw alcohol concentration contract extractum;

B, get Resina garciniae extractum, Rhizoma Bletillae powder, Indigo Naturalis powder, Fructus Gardeniae powder, Concha Arcae powder, add starch and press method for preparing tablet thereof and mix, the damping material, the system granule is dried, and granulate adds 0.5% magnesium stearate, and tabletting gets final product.

Claims (1)

1, a kind of Gamboge preparation for the treatment of multiple malignant tumor, it is made by the raw material of following parts by weight: Resina garciniae 25-35, Pseudobulbus Bletillae (Rhizoma Bletillae) 15-25, Indigo Naturalis 40-60, Fructus Gardeniae 20-30, Concha Arcae 30-40;

Its preparation technology is as follows:

A, Resina garciniae raw alcohol concentration contract extractum;

B, get Resina garciniae extractum, Rhizoma Bletillae powder, Indigo Naturalis powder, Fructus Gardeniae powder, Concha Arcae powder, add starch and press method for preparing tablet thereof and mix, the damping material, the system granule is dried, and granulate adds 0.5% magnesium stearate, and tabletting gets final product.