CN103393908B - Product for treating systemic lupus erythematosus and rheumatism and preparation method thereof - Google Patents

Product for treating systemic lupus erythematosus and rheumatism and preparation method thereof Download PDF

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CN103393908B
CN103393908B CN201310263419.1A CN201310263419A CN103393908B CN 103393908 B CN103393908 B CN 103393908B CN 201310263419 A CN201310263419 A CN 201310263419A CN 103393908 B CN103393908 B CN 103393908B
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aqueous extract
radix
medicine
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彭都
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GUANGDONG SANCAI SHIQI PHARMACEUTICAL Co.,Ltd.
Sancai Shiqi Pharmaceutical Co ltd
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GUANGDONG SUCCHI SHIQI PHARMACEUTICAL Co Ltd
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Abstract

The invention provides a product for treating systemic lupus erythematosus and rheumatism and a preparation method thereof, and belongs to the field of Chinese patent medicine and pharmacy technology thereof. The invention is characterized in that the product is obtained from common submerged fermentation of a water extract of the following traditional Chinese medicines and a morel mother strain: 20-40 parts of radix clematis, 20-40 parts of Ligusticum wallichii, 20-40 parts of madder, 20-40 parts of late silkworm excrement, 20-40 parts of red adzuki beans, 20-40 parts of angelica, 20-40 parts of cinnamon and 20-40 parts of semen allii tuberosi. In some embodiments, a fetus cervi powder is added in the submerged fermentation, so that the product is rich in plant polypeptides from traditional Chinese medicines. Fungus polysaccharide of the morel, animal polysaccharide from the fetus cervi powder and coordination compounds of the three polysaccharides have substantial effects on integrally enhancing immunity of the patients. The product provided by the invention can simultaneously treat principal and subordinate symptoms, and have no toxic or side effect, and fast effectiveness.

Description

Systemic lupus erythematosus and rheumatismal goods and preparation method thereof
Technical field
The present invention relates to Chinese medicine formula and pharmaceutical technology, particularly a kind of systemic lupus erythematosus and rheumatismal goods and preparation method thereof.
Background technology
Systemic lupus erythematosus (sle) systemic lupus erythematosus; SLE, is a kind of diffusivity, general autoimmune disease, mainly involves mucocutaneous, skeletal muscle, kidney and central nervous system, can also involve multiple organs and the systems such as lung, heart, blood simultaneously, shows various clinical symptoms; In serum, multiple autoantibody and crucial immunological abnormality can be detected.
Pathogenesis
(1) disease susceptibility:
SLE is not the heredopathia of term single gene, and its morbidity is relevant to multiple genetic abnormality, is a kind of polygenic disease, as the morbidity significant correlation of HLA-DR2 and HLA-DR3 molecule and each hypotype and SLE; The C4a genetic defect of isozygotying is relevant to the risk of SLE morbidity; In addition, SLE also has certain dependency with C1q, C1r/s and C2 deficiency.
(2) immunocyte disorder: SLE patient's autoantibody produces relevant with the immunocyte system disorders such as T cell, B cell and mononuclear cell.Also can there is abnormal immunologic tolerance in T cell and B cell disorder.In SLE patient body, except anti-ds-DNA antibody titre significantly raises, nucleosome is the pathogenetic antigen that inspires of SLE disease.In addition, DNA of bacteria has characteristic nucleic acid motif, can directly stimulate TLR, has potential immune auxiliary property, can induce susceptible individual to produce anti-DNA antibody.In the pathogenic process of SLE, the cross reaction of exotic antigen inspires the immunne response of body, and autoantigen has maintained the lasting generation of ANA.
(3) risk factor
Inherited genetic factors and body fluid microenvironment provide SLE susceptible background, but the generation of SLE or state of an illness activity may be relevant with environment or other exogenous stimulations.Wherein, infection is one of important factor in order.Infection can and affect immunoloregulation function and inducing specific immunne response by molecular simulation; Stress affect immune cell function by promoting neuroendocrine to change; Diet can affect the generation of inflammatory mediator; Drugs comprise medicine, the immunogenicity of scalable cellular responsibility and autoantigen; The physical factors such as ultraviolet radiation can cause inflammation and tissue injury.There is very big-difference to the damage of Different Individual in these risk factors.
Several years before clinical symptoms occurs can there is serology abnormal change in many SLE patients, from pathogenesis, SLE is the disease of progressivity, first shows as autoantibody and produce, and under the stimulation of certain factor, occurs clinical symptoms.Posteriori risk factor can cause autoantigen release, immune complex to form and inspire cytokine and produce.
Clinical symptoms:
The morbidity of systemic lupus erythematosus (sle) can suddenly can be delayed, and clinical manifestation is varied.The atypical manifestations that the patient of early stage light disease often only has triangular web or organ to get involved, along with its clinical manifestation meeting of development of the course of disease becomes increasingly complex, can show as the clinical symptoms that multiple organs and systems are got involved.Whole body performance comprises heating, fatigue, weak and lose weight etc.
(1) clinical manifestation of common get involved tissue and organ:
1) mucocutaneous: butterfly erythema, plate-like skin lesion, photosensitivity, erythema or pimple, oral cavity, pudendum or rhinelcos, alopecia etc.
2) articular muscle: arthralgia, swollen joint, myalgia, myasthenia, ischemic osteonecrosis etc.
3) blood system: leukopenia, anemia, thrombocytopenia, lymphadenectasis, splenomegaly etc.
4) nervous system: 19 kinds of performances such as headache, peripheral neuropathy, epilepsy, tic, psychological problem.
5) cardiovascular system: pericarditis, myocarditis, endocarditis etc.
6) vascular lesion: Raynaud phenomenon, livedo reticularis, artery and vein thromboembolism and habitual abortion etc.
7) pleura and lung: pleuritis, interstitial pulmonary fibrosis, lupus pneumonia, pulmonary hypertension and adult respiratory distress syndrome etc.
8) kidney: albuminuria hematuria, cylinderuria, nephrotic syndrome and renal insufficiency etc.
9) digestive system: stomachache, diarrhoea, feel sick, vomiting, peritonitis and pancreatitis etc.
Due to the complicated clinical manifestation of systemic lupus erythematosus (sle), in treatment, emphasize the principle of early stage, individuation scheme and drug combination.Have or not organ to be involved state of an illness activity according to patient and select different therapeutic schemes.To actively medication treatment of patient with severe symptoms, after state of an illness control, maintain treatment.
At present, there is not yet the extraordinary medicine that is used for the treatment of systemic lupus erythematosus (sle) of effect, particularly for the medicine of systemic lupus erythematosus (sle) that shows as the rheumatism symptoms such as rheumatism arthralgia, swollen joint, myalgia, myasthenia, ischemic osteonecrosis.
Rheumatic arthritis and rheumatoid arthritis, be the numbness that the traditional Chinese medical science is assert, the real systemic lupus erythematosus (sle) category that belongs to, and the slightly different part in phase ridge, traditional Chinese medical science meaning numbness is ridge, cold, wet three gas are mixed extremely.Method for the treatment of is stopped nothing but the heresy of wind, cold, wet three gas, and arthromyodynia can heal, and the most difficult work of arthromyodynia, obtains it to want, and is just being not difficult also.A traditional Chinese medical science point heresy enters internal organs and opinion is controlled, Therapeutic Method or method have by numbness pellet, six gentleman plus-minuss, stomach warming disappear wet red, loose numbness soup, Radix Morindae Officinalis soup, attack that numbness is loose, JINU soup, Li Bentang, anti-osmanthus art Siberian cocklebur are loose, correction is by evil soup, adaptive soup.These medicines have certain effect for the single symptom for the treatment of lupus erythematosus, still, there is no positive effect for showing as rheumatismal lupus erythematosus.
Summary of the invention
The blank and the demand that exist according to above-mentioned field, the invention provides a kind of systemic lupus erythematosus and rheumatismal goods and preparation method thereof, can treating both the principal and secondary aspects of a disease, have no side effect, and instant effect.
One is used for the treatment of systemic lupus erythematosus (sle) and rheumatismal goods, it is characterized in that: the aqueous extract of raw material of Chinese medicine medicine and the product of the common submerged fermentation of morchella mother culture that are following components by weight percent: 20~40 parts of Radix Clematidis, 20~40 parts of Rhizoma Chuanxiongs, 20~40 parts, Radix Rubiae, 20~40 parts of late Bombyx mori L.s, 20~40 parts of Semen Phaseolis, 20~40 parts of Radix Angelicae Sinensis, 20~40 parts of Cortex Cinnamomis, 20~40 parts of Semen Allii Tuberosi.
The raw material of Chinese medicine medicine of described components by weight percent: 20 parts of Radix Clematidis, 30 parts of Rhizoma Chuanxiongs, 40 parts, Radix Rubiae, 40 parts of late Bombyx mori L.s, 30 parts of Semen Phaseolis, 40 parts of Radix Angelicae Sinensis, 20 parts of Cortex Cinnamomis, 30 parts of Semen Allii Tuberosi.
The raw material of Chinese medicine medicine of described components by weight percent: 40 parts of Radix Clematidis, 20 parts of Rhizoma Chuanxiongs, 20 parts, Radix Rubiae, 30 parts of late Bombyx mori L.s, 20 parts of Semen Phaseolis, 30 parts of Radix Angelicae Sinensis, 40 parts of Cortex Cinnamomis, 20 parts of Semen Allii Tuberosi.
The raw material of Chinese medicine medicine of described components by weight percent: 30 parts of Radix Clematidis, 40 parts of Rhizoma Chuanxiongs, 30 parts, Radix Rubiae, 20 parts of late Bombyx mori L.s, 40 parts of Semen Phaseolis, 20 parts of Radix Angelicae Sinensis, 30 parts of Cortex Cinnamomis, 40 parts of Semen Allii Tuberosi.
The raw material of Chinese medicine medicine of described components by weight percent: 30 parts of Radix Clematidis, 30 parts of Rhizoma Chuanxiongs, 30 parts, Radix Rubiae, 30 parts of late Bombyx mori L.s, 30 parts of Semen Phaseolis, 30 parts of Radix Angelicae Sinensis, 30 parts of Cortex Cinnamomis, 30 parts of Semen Allii Tuberosi.
The weight of described aqueous extract is 5~8 times of described raw material of Chinese medicine medicine gross weight.
The condition of described submerged fermentation is 25 degrees Celsius, 72~144 hours.
Described morchella mother culture refers to that test tube is female plants, and inoculum concentration is in aqueous extract, to inoculate female kind of described test tube of 5~15 pipe 18mm × 180mm specifications described in every 100kg.
When inoculation, also in the aqueous extract of described raw material of Chinese medicine medicine, add that to have Embryo cervi powder, additional proportion be 60~100g Embryo cervi powder: the aqueous extract of 100kg raw material of Chinese medicine medicine.
Described morchella mother culture refers to liquid bacteria screw kind, inoculum concentration is that the volume ratio of liquid bacteria screw kind and described aqueous extract is 10~20:100, described liquid bacteria screw kind is that female kind of Morchella esculenta (L.) Pers test tube obtains as solution culture fermentation 74 hours using the described aqueous extract that contains following adjuvant, and described adjuvant accounts for 5~8%(w/w in described fluid medium); The composition by weight of described adjuvant is: 5 parts of dipotassium hydrogen phosphates, 5 parts of potassium dihydrogen phosphates, 2 parts, zinc sulfate, 50 parts of white sugar, 10 parts, Embryo cervi powder, 20 parts of yeast extracts, 100 parts of nutrient agars.
Medicine taking above-mentioned arbitrary goods as the systemic lupus erythematosus of effective ingredient.
The preparation method of above-mentioned arbitrary goods, its step is as follows:
(1) component takes raw material of Chinese medicine medicine by weight;
(2) add the water of 5~6 times of raw material of Chinese medicine medicine total amounts, big fire is boiled, and little fire decocts, and each 0.5 hour, filters extracting juice;
(3) repeating step (2) 4~5 times, collects all filtrate and obtains the aqueous extract that weight is 5~8 times of raw material of Chinese medicine medicine total amounts; Aqueous extract described in normal temperature high voltage deactivation;
(4) to deactivation and be cooled in the aqueous extract of room temperature and inoculate morchella mother culture;
(5) submerged fermentation: condition is 25 degrees Celsius, 72~144 hours.
The invention provides the goods that a kind of effective treatment shows as rheumatismal system lupus erythematosus.Good compatibility carried out obtaining aqueous extract after water extraction for the effective crude drug of rheumatism symptom, and then inoculation morchella mother culture carries out submerged fermentation and obtains.In the raw material of Chinese medicine medicine of compatibility, Radix Clematidis, Rhizoma Chuanxiong, Radix Rubiae, late Bombyx mori L. four Chinese medicine complement each other to complement one another and are used to patient's relaxing muscles and tendons to promote blood circulation, remove the diseases such as rheumatic arthralgia; Semen Phaseoli is used for removing dampness, removing toxic substances and promoting pus discharge, and Cortex Cinnamomi, Semen Allii Tuberosi are supporing yang for cold expelling righting, promoting blood circulation, liver and kidney tonifying, three taste medicines for fundamentally removing the pathogenic immanent cause of the Patients with SLE that shows as rheumatism symptom.Morchella esculenta (L.) Pers is rich in the necessary aminoacid of multiple human body, in the metabolite that fermentation produces, is rich in granulose, stimulates human immune system to produce multiple nonspecific antibody, and enhancing body resistance, reaches effect that antiviral and anti-microbial pathogen infect.
Goods of the present invention have significant curative effect equally for simple rheumatisant.
In some embodiments of the present invention, morchella mother culture is that test tube mother plants (test tube slant is female plants), and directly test tube mother plants in the aqueous extract that is inoculated in raw material of Chinese medicine medicine and carries out submerged fermentation, each component complements each other and carries out systematic treating for the systemic lupus erythematosus (sle) disease of rheumatism symptom, various compositions are not only brought into play the function of self, and submerged fermentation makes the bacterium of vegetable polysaccharides in raw material of Chinese medicine medicine and Morchella esculenta (L.) Pers have an opportunity to stop to close the more complicated macromole heteropolysaccharide of formation more, take after these these goods, patient's immune system will be subject to vegetable polysaccharides, the active of granulose and their Suffix compound three class macromolecular substances stimulates, this makes goods of the present invention in enhancing human body immunity power, body is initiatively obtained for multiple pathogen, the resistance of virus, can eliminate lupus erythematosus deterioration and development that body causes due to infection, treating both the principal and secondary aspects of a disease on the whole.Clinical trial checking, these goods of the present invention are treated the systemic lupus erythematosus (sle) of rheumatism symptoms, have the curative effect of highly significant.
In most of embodiment in the present invention, be that the female kind of test tube (test tube slant is female plants) is inoculated in aqueous extract process at morchella mother culture, also added Embryo cervi powder to participate in submerged fermentation.Embryo cervi powder itself possesses effect of enriching yin and nourishing kidney, be rich in 17 seed amino acids and polysaccharose substance, Embryo cervi powder itself has positive left and right for patient's vital base and primordial QI consolidating, and in preparation process, submerged fermentation makes the vegetable polysaccharides in raw material of Chinese medicine medicine, in the granulose of Morchella esculenta (L.) Pers and Embryo cervi powder, the animal polysaccharide molecule Fa Sheng Suffix that has an opportunity closes the more complicated macromole heteropolysaccharide of formation, take after these goods, patient's immune system will be subject to vegetable polysaccharides, granulose, the active of animal sources polysaccharide and their Suffix compound four class macromolecular substances stimulates, this makes goods of the present invention in enhancing human body immunity power, body is initiatively obtained for multiple pathogen, the resistance of virus, effect that the lupus erythematosus that removal body causes due to infection worsens and develops is more remarkable, not only take stopgap measures but also consolidate on the whole.
In some embodiments of the present invention, morchella mother culture is liquid bacteria screw kind.Liquid bacteria screw kind is before submerged fermentation, with part aqueous extract as fluid medium, and in liquid medium within, adding the adjuvants such as dipotassium hydrogen phosphate, potassium dihydrogen phosphate, zinc sulfate, sucrose, Embryo cervi powder, yeast extract, nutrient agar to make female fluid medium of planting, inoculation Morchella esculenta (L.) Pers test tube mother plants after fermentation and obtains.In more such embodiment, successively there is twice Fa Jiao Suffix and close process in the animal polysaccharide in vegetable polysaccharides, Embryo cervi powder in Chinese medicine and the granulose of Morchella esculenta (L.) Pers, makes the more remarkable treatment effect of the goods of these embodiment gained.
The crude drug that goods of the present invention adopt is as follows:
Radix Clematidis, Radix Clematidis another name: Radix Stemonae, Tacca chantrieri Andre, ferrum fan sweeping (sao).This product is the dry root and rhizome of dicotyledon Ranunculaceae Ranunculaceae Radix Clematidis Clematis chinensis Osbeck.Cure mainly gout insensitive impediment, rheumatic arthralgia, numb limbs and tense tendons, knee joint cold type of pain, the contracture of muscle arteries and veins, joint stuffiness, beriberi, malaria, lump in the abdomen, tetanus, tonsillitis, all a fishbone or other bone caught in the throat pharynxs.
Rhizoma Chuanxiong, Rhizoma Chuanxiong calls Rhizoma Chuanxiong, and medicinal part is the rhizome of samphire Rhizoma Chuanxiong.For pain in chest and hypochondrium, rheumatic arthralgia, lump in the abdomen caking, skin infection swells and ache, fall and flutter the pain of injury, menoxenia, amenorrhea dysmenorrhea, puerperal the disease such as stasis of blood pain.
Radix Rubiae, is the dry root and rhizome of Maguireothamnus speciosus Radix Rubiae Rubia cordifolia L., has effect of cooling blood for hemostasis, blood circulation promoting and blood stasis dispelling.Cure mainly the diseases such as heat in blood spitting of blood, postpartum stagnation stomachache, traumatic injury, rheumatic arthralgia.
Late Bombyx mori L., the dry feces of Faeces Bombycis Bombycidae animal bombyx mori Bombyx mori L. larva.Dispeiling pathogenic wind and removing dampness, heat clearing and blood circulation promoting.Dispelling the wind and dampness pathogens, munbness, joint be unsuccessful, sharply vomit and diarrhoea, convulsion, and muscles and bones is unsuccessful, blood stasis, wind syndrome of head acute conjunctivitis in lumbar and pedal pain, abdomen.
Semen Phaseoli, the seed of dicotyledon pulse family Leguminosae Semen Phaseoli Phaseolus calcaratus Roxb. or Semen Phaseoli Phaseolus angularisWight.Inducing diuresis and reducing edema (jaundice, dysentery, has blood in stool, carbuncle for edema, beriberi), heat clearing away jaundice eliminating, removing toxic substances and promoting pus discharge.
Cortex Cinnamomi, the dry bark of canella Cortex Cinnamomi Cinnamomum cassia Presl, mends fire supporing yang, let the fire back to its origin, dispersing cold for relieving pain, promoting blood circulation to restore menstrual flow.Warming the spleen and stomach, removing accumulated cold, promoting blood circulation.
Semen Allii Tuberosi: Semen Allii Tuberosi is the dry mature seed of liliaceous plant Folium Allii tuberosi, Semen Allii Tuberosi another name Semen Allii Tuberosi, Folium Allii tuberosi core, Semen Allii Tuberosi has effect of liver and kidney tonifying, tonifying YANG controlling nocturnal emission with astringent drugs, Semen Allii Tuberosi has treatment impotence due to deficiency of the kidney, soreness of the waist and knees, seminal emission, frequent micturition, turbid urine, the clear rare effect of leukorrhagia, and hyperactivity of fire caused by deficiency of YIN person avoids and uses Semen Allii Tuberosi.
Embryo cervi powder: Embryo cervi powder is to make with the tire of Cervus nippon Temminck or Cervus elaphus linnaeus.In Embryo cervi, contain 17 seed amino acids, 22 kinds of inorganic constituents, multivitamin and ketone, estrange sulfate, estradiol and 6 kinds of specific liposoluble constituents, according to " compendium of Materia Medica" record: " all poison of Embryo cervi menstruation-regulating face-beautifying solution ", there is replenishing vital essence and blood, return the effect of few sun, be women nourish take good care of, the superfine product of slow down aging.Commercially available.
Morchella esculenta (L.) Pers: latin name: Morehella esculenta (L.) Pers, Morchella esculenta (L.) Pers is foremost delicious food bacterium in ascomycetes, the aminoacid that its cap part contains isoleucine, leucine, lysine, methionine, phenylalanine, threonine and 7 kinds of needed by human of valine, sweet cold nontoxic, useful the intestines and stomach, aid digestion, phlegm-eliminiating and qi-regulating, kidney invigorating and YANG supporting, supplementing the brain effect such as refresh oneself; Morchella esculenta (L.) Pers, containing the polysaccharide and antibacterial, the antiviral active component that suppress tumor, has all multiactions such as enhancing human body immunity power, resisting fatigue, antiviral, inhibition tumor.But not retrieving Morchella esculenta (L.) Pers, inventor has effectively treatment lupus erythematosus or rheumatismal report of participation.
Those skilled in the art, can content according to the present invention obtain goods of the present invention, and using these goods as effective ingredient, add pharmaceutically acceptable auxiliary element, thereby make the medicine of various dosage forms as excipient, suspending agent, slow releasing agent, flavoring agent etc.These medicines all belong to same design of the present invention, therefore also protect in this request.
The present invention also provides the preparation method of goods of the present invention.Preparation method is divided into two schemes:
One be extract Chinese medicine aqueous extract after, the female kind of direct inoculation test tube carried out submerged fermentation.During some is implemented, also add Embryo cervi powder to participate in submerged fermentation, additional proportion is 60~100g Embryo cervi powder: the aqueous extract of 100kg raw material of Chinese medicine medicine.
Another kind is, after extracting Chinese medicine aqueous extract, part aqueous extract is as the fluid medium expanding propagation morchella mother culture that is used for fermenting, wherein in fluid medium, add the adjuvant including Embryo cervi powder, expanding propagation and morchella mother culture mycelia liquid, and then (10~20:100) is inoculated in the aqueous extract of raw material of Chinese medicine medicine according to a certain volume.
Detailed description of the invention
It is in order further to understand better the present invention that following embodiment is provided; be not limited to described preferred forms; content of the present invention and protection domain are not construed as limiting; anyone under enlightenment of the present invention or by the present invention, combines with the feature of other prior aries and any and the present invention of drawing is identical or akin product, within all dropping on protection scope of the present invention.
The preparation of No. 1.1 goods of embodiment
The preparation of step 1. Chinese medicine aqueous extract
Raw material of Chinese medicine and weight portion thereof: 20 parts of Radix Clematidis, 30 parts of Rhizoma Chuanxiongs, 40 parts, Radix Rubiae, 40 parts of late Bombyx mori L.s, 30 parts of Semen Phaseolis, 40 parts of Radix Angelicae Sinensis, 20 parts of Cortex Cinnamomis, 30 parts of Semen Allii Tuberosi.
(1) take altogether 28kg by above-mentioned raw materials medicine component;
(2) add the water of 5~6 times of raw material of Chinese medicine medicine total amounts, big fire is boiled, and little fire decocts, and each 0.5 hour, filters extracting juice;
(3) repeat (2) 5 times, collect all filtrate and must amount to the about 150kg Chinese medicine of weight aqueous extract.
Step 2. is prepared the female liquid of planting of Morchella esculenta (L.) Pers. Mycelium
Material: Morchella esculenta (L.) Pers (Morehellaspp esculenta (L.) Pers) is female plants, Chinese agriculture microorganism fungus kind preservation administrative center (Agricultural Culture Collection of China english abbreviation ACCC), deposit number 51837.Specification: test tube slant kind (test tube specification 18mm × 180mm, approximately 40 milliliters), contact method 010-68918636010-68918651010-68918683Accc@caas.ac.cn.
Above-mentioned morchella mother culture, applicant's laboratory also has preservation, and is prepared into the female kind of test tube mycelia, within 20 years from the applying date, can provide for experimentation to the public.Also can be to be purchased approach to obtain for morchella mother culture of the present invention, there is no special requirement.
Material:
1. the Chinese medicine aqueous extract of step 1
2. nutrient agar; (Shanghai health and happiness culture medium factory of Chinese medicine insecticide biotechnology development corporation, Ltd.)
3. yeast extract; (Beijing bispin microbiological culture media products factory)
4. dipotassium hydrogen phosphate; (chemical plant, the western Gansu Province of Shantou, Guangdong)
5. zinc sulfate (analytical pure); (tower chemical plant, upper Haixing County)
6. Embryo cervi powder; (Wen Julu product agency, Shuangyang District)
7. potassium dihydrogen phosphate; (Guang Hui chemical plant, Qingdao City)
8. white sugar; (supermarket purchase)
9. potassium permanganate; (Tianjin Heng Xing chemicals company limited)
10. formalin; (Jinan, Shandong Province chemical reagent work)
The female test tube of planting of 11. mycelia.
Utensil:
1.500ml vial;
2. portable pressure cooker, electric coal double-purpose; (Shanghai Shen Yisan factory)
3. shaking table: D4-900; (Jiangsu Tai Lunshi experimental facilities factory)
4. superclean bench;
5. alcohol burner;
6. hook, rake, pin, cutter;
7. match;
8. sterilization Cotton Gossypii;
9.75% ethanol;
10. rubber band.
Method:
1) in the Chinese medicine aqueous extract obtaining in 15kg step 1, add respectively 50g dipotassium hydrogen phosphate, 50g potassium dihydrogen phosphate, 20g zinc sulfate, 100g Embryo cervi powder, 500g white sugar, 200g yeast extract, stir and heat to 100 DEG C, put into 1000g nutrient agar, after dissolving, add again Chinese medicine aqueous extract and make 25kg dirty solution.
2) 12.5kg dirty solution is injected in 500ml vial, every bottle of 400ml, has to obtain 12 bottles altogether, inserts the inherent 0.012MP/cm of portable pressure cooker 2, 30min, is cooled to 28 DEG C~34 DEG C after taking-up, put into superclean bench.
3) culture medium after instrument and utensil and deactivation is put into superclean bench, inserts in the vessel that fill 50% formalin 30ml with 30g potassium permanganate, and hook, rake, pin, the cutter of inoculation use are put into this vessel sterilizing 30min.Will be in vitro Morchella esculenta (L.) Pers. Mycelium is female plants, be cut into 3 parts, in the dirty solution that every part is accessed respectively 400ml/ bottle, 120min~150min rests.
4) on shaking table with 20 times/min, vibrate and within 74 hours, obtain the female liquid of planting of Morchella esculenta (L.) Pers. Mycelium.
Step 3. submerged fermentation
The Chinese medicine aqueous extract that step 1 is obtained is placed in and is entitled as fermentation tank that " cover of vaccine culturing-pot for edible and culture tank " patent No. is ZL03270560.3 as fermentation substrate.And water at atmospheric pressure steam deactivation 12 hours in the boiler that fermentation tank to be pushed to " saturated vapor pressure-less boiler " patent No. be ZL200320126611.8.When in tank, substrate is cooled to 28~34 DEG C, be called the inoculation syringe that " edible fungus liquid injection rod and the syringe that comprises this injection rod " patent No. is ZL200320126960.X by name, the female liquid of planting of the Morchella esculenta (L.) Pers. Mycelium that step 2 is prepared is injected in Chinese medicine aqueous extract; Inoculum concentration: the female volume ratio of planting liquid and Chinese medicine aqueous extract of Morchella esculenta (L.) Pers. Mycelium is 20:100, and submerged fermentation 72~144 hours, puts tank under 18~30 DEG C of environment.
Step 4. is produced medicine:
Put the submerged fermentation obtaining after tank, concentrate, dry, the powder 8kg that sieves to obtain, part retains powder state, makes capsule, and every containing 0.35g powder.
No. 2.2 goods of embodiment
The preparation of step 1. Chinese medicine aqueous extract
Raw material of Chinese medicine and weight portion thereof: the raw material of Chinese medicine medicine of described components by weight percent: 40 parts of Radix Clematidis, 20 parts of Rhizoma Chuanxiongs, 20 parts, Radix Rubiae, 30 parts of late Bombyx mori L.s, 20 parts of Semen Phaseolis, 30 parts of Radix Angelicae Sinensis, 40 parts of Cortex Cinnamomis, 20 parts of Semen Allii Tuberosi.
(1) take altogether 20kg by above-mentioned raw materials medicine component;
(2) add the water of 5~6 times of raw material of Chinese medicine medicine total amounts, big fire is boiled, and little fire decocts, and each 0.5 hour, filters extracting juice;
(3) repeat (2) 5 times, collect all filtrate and must amount to the about 150kg Chinese medicine of weight aqueous extract.
Other step is with embodiment 1.
Just the female volume ratio of planting liquid and Chinese medicine aqueous extract of Morchella esculenta (L.) Pers. Mycelium is 15:100.
No. 3.3 goods preparations of embodiment
The preparation of step 1. Chinese medicine water extract
Raw material of Chinese medicine and weight portion thereof: 30 parts of Radix Clematidis, 40 parts of Rhizoma Chuanxiongs, 30 parts, Radix Rubiae, 20 parts of late Bombyx mori L.s, 40 parts of Semen Phaseolis, 20 parts of Radix Angelicae Sinensis, 30 parts of Cortex Cinnamomis, 40 parts of Semen Allii Tuberosi.
(1) take altogether 35kg by above-mentioned raw materials medicine component;
(2) add the water of 5~6 times of raw material of Chinese medicine medicine total amounts, big fire is boiled, and little fire decocts, and each 0.5 hour, filters extracting juice;
(3) repeat (2) 5 times, collect all filtrate and must amount to the about 150kg Chinese medicine of weight aqueous extract.
The female kind of Morchella esculenta (L.) Pers test tube that step 2. is Accc51837 with the preserving number of buying carried out submerged fermentation
The Chinese medicine aqueous extract that step 1 is obtained is placed in and is entitled as fermentation tank that " cover of vaccine culturing-pot for edible and culture tank " patent No. is ZL03270560.3 as fermentation substrate.And water at atmospheric pressure steam deactivation 12 hours in the boiler that fermentation tank to be pushed to " saturated vapor pressure-less boiler " patent No. be ZL200320126611.8.When in tank, substrate is cooled to 28~34 DEG C, be called the inoculation syringe that " edible fungus liquid injection rod and the syringe that comprises this injection rod " patent No. is ZL200320126960.X by name, in every 100kg Chinese medicine aqueous extract, inoculate 5(18mm × 180mm) the female kind of Morchella esculenta (L.) Pers test tube, under 18~30 DEG C of environment, carry out submerged fermentation, after 72~144 hours, put tank.
Step 3. is produced medicine:
Put the submerged fermentation obtaining after tank, concentrate, dry, the powder 7.8kg that sieves to obtain, part retains powder state, makes capsule, and every containing 0.35g powder.
No. 4.4 goods preparations of embodiment
Be female (test tube specification 18mm × 180mm), the preserving number: Accc51837 of planting of test tube of buying from Chinese Academy of Agricultural Sciences's agricultural microorganism fungus kind preservation center for the morchella mother culture of the present embodiment.
Applicant's laboratory also has preservation, within 20 years from the applying date, can provide for experimentation to the public.
The preparation of step 1. Chinese medicine aqueous extract
Raw material of Chinese medicine and weight portion thereof: 33 parts of Rhizoma Pinelliae (processed with Rhizoma Zingiberis Recens)s, 32 parts, Poria, 28 parts of Ramulus Uncariae Cum Uncis, 26 parts of Rhizoma Acori Graminei, 24 parts of Herba Dendrobiis, 35 parts of Arisaema Cum Bile, 45 parts of Pericarpium Citri Reticulatae, 29 parts of golden bell cores, 34 parts of Radix Scrophulariae, 27 parts of the Radix Paeoniae Albas, 31 parts of Bulbus Fritillariae Cirrhosaes.
(1) take altogether 25kg by above-mentioned raw materials medicine component;
(2) add the water of 5~6 times of raw material of Chinese medicine medicine total amounts, big fire is boiled, and little fire decocts, and each 0.5 hour, filters extracting juice;
(3) repeat (2) 5 times, collect all filtrate and must amount to the about 150kg Chinese medicine of weight aqueous extract.
The female kind of Morchella esculenta (L.) Pers test tube that step 2. is Accc51837 with the preserving number of buying carried out submerged fermentation
The Chinese medicine aqueous extract that step 1 is obtained is placed in and is entitled as fermentation tank that " cover of vaccine culturing-pot for edible and culture tank " patent No. is ZL03270560.3 as fermentation substrate.And water at atmospheric pressure steam deactivation 12 hours in the boiler that fermentation tank to be pushed to " saturated vapor pressure-less boiler " patent No. be ZL200320126611.8.When in tank, substrate is cooled to 28~34 DEG C, be called the inoculation syringe that " edible fungus liquid injection rod and the syringe that comprises this injection rod " patent No. is ZL200320126960.X by name, in every 100kg Chinese medicine aqueous extract, inoculate the female kind of 15 pipes (18mm × 180mm) Morchella esculenta (L.) Pers test tube, add 150g Embryo cervi powder simultaneously, under 18~30 DEG C of environment, carry out submerged fermentation, after 144 hours, put tank.
Step 3. is produced medicine:
Put the submerged fermentation obtaining after tank, concentrate, dry, the powder 7.8kg that sieves to obtain, part retains powder state, makes capsule, and every containing 0.35g powder.
Experimental example. clinical statistics
Case 46 examples are observed in outpatient service.
Be systemic lupus erythematosus (sle) and rheumatic patient's 13 examples that show as arthralgia by Western medicine diagnose, be divided into two batches:
A collection of 6 people take No. 1 goods of the present invention, and 3 times/day, 3/time (capsule) or 10g/ time (powder), arthralgia (week) after a course for the treatment of alleviates obviously, and after fortnight, various merging symptoms are as heating, weak, the symptoms such as fatiguability obviously alleviate even disappearance.
A collection of 7 people take No. 4 goods of the present invention, 3 times/day, 3/time (capsule) or 10g/ time (powder), statistics effect arthralgia (week) after a course for the treatment of alleviates obviously, after fortnight, various merging symptoms are as heating, weak, the symptoms such as fatiguability obviously alleviate even disappearance, and effective percentage is 100%.
By Western medicine diagnose, in body, detect the rheumatism factor and be diagnosed as rheumatismal patient's 33 examples;
Be divided into 4 batches, have respectively 8,8,8,9 patients, take respectively 1~No. 4 goods of the present invention, 3 times/day, 3/time (capsule) or 10g/ time (powder).Take after medicine of the present invention, basic 2 days, patient's readme joint pain alleviated, and joint has hotness; Take continuously three weeks, joint flexibility ratio obviously improves, and pain disappears substantially.Statistics effective percentage 96%.

Claims (7)

1. one kind is used for the treatment of systemic lupus erythematosus (sle) and rheumatismal goods, it is characterized in that: the aqueous extract of raw material of Chinese medicine medicine and the product of the common submerged fermentation of morchella mother culture that are following components by weight percent: 20~40 parts of Radix Clematidis, 20~40 parts of Rhizoma Chuanxiongs, 20~40 parts, Radix Rubiae, 20~40 parts of late Bombyx mori L.s, 20~40 parts of Semen Phaseolis, 20~40 parts of Radix Angelicae Sinensis, 20~40 parts of Cortex Cinnamomis, 20~40 parts of Semen Allii Tuberosi
The weight of described aqueous extract is 5~8 times of described raw material of Chinese medicine medicine gross weight: the condition of described submerged fermentation is 25 degrees Celsius, 72~144 hours.
2. goods according to claim 1, is characterized in that: the raw material of Chinese medicine medicine composition of described components by weight percent is one of following:
20 parts of Radix Clematidis, 30 parts of Rhizoma Chuanxiongs, 40 parts, Radix Rubiae, 40 parts of late Bombyx mori L.s, 30 parts of Semen Phaseolis, 40 parts of Radix Angelicae Sinensis, 20 parts of Cortex Cinnamomis, 30 parts of Semen Allii Tuberosi;
40 parts of Radix Clematidis, 20 parts of Rhizoma Chuanxiongs, 20 parts, Radix Rubiae, 30 parts of late Bombyx mori L.s, 20 parts of Semen Phaseolis, 30 parts of Radix Angelicae Sinensis, 40 parts of Cortex Cinnamomis, 20 parts of Semen Allii Tuberosi;
30 parts of Radix Clematidis, 40 parts of Rhizoma Chuanxiongs, 30 parts, Radix Rubiae, 20 parts of late Bombyx mori L.s, 40 parts of Semen Phaseolis, 20 parts of Radix Angelicae Sinensis, 30 parts of Cortex Cinnamomis, 40 parts of Semen Allii Tuberosi; With
30 parts of Radix Clematidis, 30 parts of Rhizoma Chuanxiongs, 30 parts, Radix Rubiae, 30 parts of late Bombyx mori L.s, 30 parts of Semen Phaseolis, 30 parts of Radix Angelicae Sinensis, 30 parts of Cortex Cinnamomis, 30 parts of Semen Allii Tuberosi.
3. goods according to claim 1 and 2, is characterized in that: described morchella mother culture refers to that test tube is female plants, and inoculum concentration is in the aqueous extract of raw material of Chinese medicine medicine described in every 100kg, to inoculate female kind of described test tube of 5~15 pipe 18mm × 180mm specifications.
4. goods according to claim 1 and 2, it is characterized in that: described morchella mother culture refers to liquid bacteria screw kind, inoculum concentration is that the volume ratio of liquid bacteria screw kind and described aqueous extract is 10~20:100, described liquid bacteria screw kind is that female kind of Morchella esculenta (L.) Pers test tube obtains as solution culture fermentation 74 hours using the described aqueous extract that contains following adjuvant, and described adjuvant accounts for 5~8% (w/w) in described fluid medium; The composition by weight of described adjuvant is: 5 parts of dipotassium hydrogen phosphates, 5 parts of potassium dihydrogen phosphates, 2 parts, zinc sulfate, 50 parts of white sugar, 10 parts, Embryo cervi powder, 20 parts of yeast extracts, 100 parts of nutrient agars.
5. systemic lupus erythematosus or the rheumatismal medicine taking the arbitrary described goods of claim 1~4 as effective ingredient.
6. the preparation method of goods described in claim 1, its step is as follows:
(1) component takes raw material of Chinese medicine medicine by weight;
(2) add the water of 5~6 times of raw material of Chinese medicine medicine total amounts, big fire is boiled, and little fire decocts, and each 0.5 hour, filters extracting juice;
(3) repeating step (2) 4~5 times, collects all filtrate and obtains the aqueous extract that weight is 5~8 times of raw material of Chinese medicine medicine total amounts; Aqueous extract described in normal temperature high voltage deactivation;
(4) to deactivation and be cooled in the aqueous extract of room temperature and inoculate morchella mother culture;
(5) submerged fermentation: condition is 25 degrees Celsius, 72~144 hours.
7. preparation method according to claim 6, described morchella mother culture refers to that test tube is female plants, and inoculum concentration is in the aqueous extract of raw material of Chinese medicine medicine described in every 100kg, to inoculate female kind of described test tube of 5~15 pipe 18mm × 180mm specifications.
CN201310263419.1A 2013-06-27 2013-06-27 Product for treating systemic lupus erythematosus and rheumatism and preparation method thereof Active CN103393908B (en)

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