CN1316279A - X-ray magnetic therapy machine for PDT therapy of cancer by combining radiatherapy with chemicotherapy and its medicine - Google Patents

X-ray magnetic therapy machine for PDT therapy of cancer by combining radiatherapy with chemicotherapy and its medicine Download PDF

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CN1316279A
CN1316279A CN 00117845 CN00117845A CN1316279A CN 1316279 A CN1316279 A CN 1316279A CN 00117845 CN00117845 CN 00117845 CN 00117845 A CN00117845 A CN 00117845A CN 1316279 A CN1316279 A CN 1316279A
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radix
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chemicotherapy
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董森
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Abstract

An X-ray magnetic therapeutic machine for the PDT of cancers features that it can output the mixed electromagneitc wave beams of X ray and laser to improve the curative effect of chemicotherapy and radiotherapy to shrink the size of tumor to less than 3 sq.cm, which can fully play the role of PDT (up to 90% or higher). A series of medicines to be used in conjuction with said machine is also disclosed.

Description

Merge chemicotherapy and dwindle the tumor body to carry out used X-ray magnetic therapy machine of PDT and medicine thereof
The present invention relates to a kind of treatment greater than 3cm 2Above tumor merges chemicotherapy and dwindles the tumor body to carry out optical dynamic therapy (PDT) used X-ray magnetic therapy machine and medicine thereof.
At present, the routine treatment of treatment cancer mainly is operation, chemicotherapy.Operation can only be applicable to the case that meets the indication of performing the operation, and has limitation.Chemicotherapy only can play most of cancer patient and dwindle lump, prolongs the effect of life, and the case that can reach recent healing seldom.And chemicotherapy also exists toxic and side effects big, drawbacks such as prognostic difference.Both made the tumor photodynamic therapy (PDT) of in the treatment and prevention of tumour science, having shown up prominently, also exist photosensitizer draw back at tumor tissues and normal surrounding tissue Chinese medicine concentration difference end greatly different distance and laser irradiation less than the position, defective and deficiency that can't the deactivation cancerous cell.
The purpose of this invention is to provide a kind ofly, can play, improve, the potentiation chemicotherapy supports that chemicotherapy dwindles the tumor body to 3cm 2Below, so that carry out photodynamic tumor treatment (PDT), a series of chemicotherapy drug combinations that make the cancer patient can reach the X-ray magnetic therapy machine of recent healing (CR) and match.
X-ray magnetic therapy machine of the present invention is mainly by (1) X-ray apparatus (180KV, 10mA, 0.5mmCU) six parts such as (2) ruby laser apparatus (available cuprous bromide copper laser replace) (3) charged particle accelerator device (4) pulsation Magnetotherapeutic apparatus (5) thermostat (6) specialty optical fiber are formed.
For the tumor body is contracted to below the 3cm2, make tumor photodynamic therapy can bring into play its curative effect, just must can be achieved in conjunction with the X-ray magnetic therapy machine in order to following chemicotherapy drug combination.Because tumor photodynamic therapy (PDT) is only applicable to esophagus, stomach, lung, liver, mammary gland, nasopharynx, rectum colon, bladder, uterus, these ten kinds of cancers of skin portion are so the anti-compound recipe complex capsule in osmanthus has designed the concrete prescription at these ten kinds of cancers.
One, the anti-compound recipe complex capsule in osmanthus
Basis side is Ramulus Cinnamomi, Poria, Cortex Moutan, Semen Persicae, each 9g of Radix Paeoniae 1..(directly making granule)
2. Herba Agrimoniae 100g, Herba Solani Lyrati 30g, Herba Solani Nigri 2 5g, Semen Arecae 15g, Rhizoma Pinelliae Preparata 10g, Radix Glycyrrhizae 5g.(system enteric-coated microcapsule granule)
1. esophageal carcinoma prescription (anti-relapse due to improper diet side, osmanthus complex capsule) Herba Agrimoniae 100g, Herba Solani Lyrati 30g, Herba Solani Nigri 25g, Semen Arecae 15g, Rhizoma Pinelliae Preparata 10g, Radix Glycyrrhizae 5g, Semen Impatientis 30g, Ramulus Cinnamomi, Poria, Cortex Moutan, Semen Persicae, each 9g of Radix Paeoniae.
2. gastric cancer prescription (osmanthus anti-stomach compound recipe complex capsule) Herba Agrimoniae 100g, Herba Solani Lyrati 30g, Herba Solani Nigri 25g, Semen Arecae 15g, Rhizoma Pinelliae Preparata 10g, Radix Glycyrrhizae 5g, Radix Codonopsis 15g, Rhizoma Atractylodis Macrocephalae 10g, Poria 15g, Ramulus Cinnamomi, Cortex Moutan, Semen Persicae, each 9g of Radix Paeoniae.
3. pulmonary carcinoma prescription (osmanthus anti-lung compound recipe complex capsule) Herba Agrimoniae 100g, Herba Solani Lyrati 30g, Herba Solani Nigri 25g, Semen Arecae 15g, Rhizoma Pinelliae Preparata 10g, Radix Glycyrrhizae 5g, Rhizoma Imperatae 30g, Radix Astragali 25g, Fructus Trichosanthis 20g, Ramulus Cinnamomi, Poria, Cortex Moutan, Semen Persicae, each 9g of Radix Paeoniae.
4. hepatocarcinoma prescription (osmanthus anti-liver compound recipe complex capsule) Herba Agrimoniae 100g, Herba Solani Lyrati 30g, Herba Solani Nigri 25g, Semen Arecae 15g, Rhizoma Pinelliae Preparata 10g, Radix Glycyrrhizae 5g, Rhizoma Curcumae, each 15g of rhizoma sparganic, Ramulus Cinnamomi, Poria, Cortex Moutan, Semen Persicae, each 9g of Radix Paeoniae.
5. breast carcinoma prescription (osmanthus resists newborn compound recipe complex capsule) Herba Agrimoniae 100g, Herba Solani Lyrati 30g, Herba Solani Nigri 25g, Semen Arecae 15g, Rhizoma Pinelliae Preparata 10g, Radix Glycyrrhizae 5g, Herba Taraxaci, each 30g of Herba Violae, Ramulus Cinnamomi, Poria, Cortex Moutan, Semen Persicae, each 9g of Radix Paeoniae.
6. nasopharyngeal carcinoma prescription (osmanthus anti-nose compound recipe complex capsule) Herba Agrimoniae 100g, Herba Solani Lyrati 30g, Herba Solani Nigri 25g, Semen Arecae 15g, Rhizoma Pinelliae Preparata 10g, Radix Glycyrrhizae 5g, Flos Lonicerae 30g, Herba Asari 10g, 5 pieces in Fructus Jujubae, Ramulus Cinnamomi, Poria, Cortex Moutan, Semen Persicae, each 9g of Radix Paeoniae.
7. rectum, colon cancer prescription (osmanthus anti-intestinal compound recipe complex capsule) Herba Agrimoniae 100g, Herba Solani Lyrati 30g, Herba Solani Nigri 25g, Semen Arecae 15g, Rhizoma Pinelliae Preparata 10g, Radix Glycyrrhizae 5g, Spina Gleditsiae 25g, Radix Sanguisorbae 30g, JIUHUANGLING 10g, Ramulus Cinnamomi, Poria, Cortex Moutan, Semen Persicae, each 9g of Radix Paeoniae.
8. bladder cancer prescription (osmanthus anti-wing compound recipe complex capsule) Herba Agrimoniae 100g, Herba Solani Lyrati 30g, Herba Solani Nigri 25g, Semen Arecae 15g, Rhizoma Pinelliae Preparata 10g, Radix Glycyrrhizae 5g, Folium Pyrrosiae 30g, Herba Hedyotidis Diffusae 15g, Rhizoma Imperatae 30g, Ramulus Cinnamomi, Poria, Cortex Moutan, Semen Persicae, each 9g of Radix Paeoniae.
9. uterus carcinoma prescription (anti-palace, osmanthus compound recipe complex capsule) Herba Agrimoniae 100g, Herba Solani Lyrati 30g, Herba Solani Nigri 25g, Semen Arecae 15g, Rhizoma Pinelliae Preparata 10g, Radix Glycyrrhizae 5g, Herba Solani Lyrati 30g, Cacumen Platycladi 30g, Ramulus Cinnamomi, Poria, Cortex Moutan, Semen Persicae, each 9g of Radix Paeoniae.
10. skin carcinoma prescription (osmanthus anti-skin compound recipe complex capsule) Herba Agrimoniae 100g, Herba Solani Lyrati 30g, Herba Solani Nigri 25g, Semen Arecae 15g, Rhizoma Pinelliae Preparata 10g, Radix Glycyrrhizae 5g, Cortex Dictamni 30g, Rhizoma Smilacis Glabrae, Radix Sophorae Tonkinensis, each 15g of Flos Lonicerae, Ramulus Cinnamomi, Poria, Cortex Moutan, Semen Persicae, each 9g of Radix Paeoniae.
Because the anti-capsular preparation methoies in above ten kinds of osmanthus are identical, thus be example with the pulmonary carcinoma prescription, the preparation method of the anti-compound recipe complex capsule in narration osmanthus.
Prescription: Ramulus Cinnamomi, Poria, Cortex Moutan, Semen Persicae, each 9g of Radix Paeoniae (directly making granule).
Method for making: the above five tastes, Ramulus Cinnamomi, Cortex Moutan, Semen Persicae extract volatile oil, and the aqueous solution after distillation device is in addition collected, medicinal residues and Poria, Radix Paeoniae two flavors decoct with water secondary, each 2h, collecting decoction, filter, the aqueous solution after filtrate and the distillation merges, and is concentrated into 1/2 of original volume, add 3 times of amount 95% ethanol, the limit edged stirs, and 24h is placed in cold preservation, filter, disgorging reclaims ethanol, put and be chilled to room temperature, filter, cleaner liquid is condensed into thick paste, adds starch and ethanol and makes granule in right amount, dry, granulate is crossed 40 mesh sieves, and granule sprays volatile oil such as adding Ramulus Cinnamomi again, mixing, promptly.
Add the flavor prescription: Herba Agrimoniae, 100g, Herba Solani Lyrati 30g, Herba Solani Nigri 25g, Semen Arecae 15g, Rhizoma Pinelliae Preparata 10g, Radix Glycyrrhizae 5g, Rhizoma Imperatae 30g, Radix Astragali 25g, Fructus Trichosanthis 20g.(system enteric-coated microcapsule granule)
Method for making:
(1) extract above nine flavors, Herba Agrimoniae is fried in shallow oil in addition, and all the other medicines decoct with water 2 times together, each 2h.Merge all decocting liquids, be concentrated to 1/2 of original volume, add 3 times of amount 95% ethanol, the limit edged stirs, and 24h is placed in cold preservation, filters, and disgorging reclaims ethanol, puts and is chilled to room temperature, filters, and filtrate is concentrated into fluid extract.
(2) parcel is transferred to above-mentioned fluid extract in the gelatin solution of 3%-5%, fully stir, it is an amount of under agitation to add water then, put in the water-bath and to keep 50 ℃, continue to stir, add 10% acetum, regulate pH value 3.5~3.6, at test under microscope, must proof produce cohesion, and see complete spheroidal microcapsule.
(3) being solidificated in above-mentioned microcapsule forms in the liquid, the formalin of adding 37%, continue to stir and further cooling, and it is an amount of to add cold distilled water, adds the frozen water cooling at reactor, makes microcapsule form liquid and reduces to 3~5 ℃, continuous stirring, behind about 1h, reuse 20% sodium hydroxide solution is adjusted pH value 8~9, and the network structure hole of gel is dwindled.
(4) after dispersion continues to stir 0.5h, add 10% living starch slurry suspension starch is fully scattered, formation one sealing coat is kept below 10 ℃ restir 1~2h between microcapsule.
(5) dry with the above-mentioned microcapsule of making, suction strainer separates, and washing eliminates moisture as far as possible, and with 40 mesh sieve system granules, the starch that progressively adds dry (60 ℃ of dry 3h) in the system granule is an amount of, makes loose particles, after one time 40 mesh sieve, and 60 ℃ of dry 2h.
(6) enteric coated Cellulose Acetate Phthalate (CAP) is made into 6% anhydrous propanone solution, get its 6 parts with 20% Lac, 1 part of mixing of ethanol solution, evenly, promptly make enteric coating solution, use air suspension coating machine that above-mentioned microcapsule granule is enteric coated then, promptly.
Osmanthus anti-lung compound recipe complex capsule
Method for making: will write out a prescription the 1. granule and the 2. enteric-coated microcapsule granule mixing of writing out a prescription, in the empty hard softgel shell of the certain specification of packing into, promptly.
Skin carcinoma ointment for promoting muscle growth prescription, method for making
Write out a prescription 1.: the Radix Angelicae Dahuricae, Radix Arnebiae (Radix Lithospermi), Radix Angelicae Sinensis, Rhizoma Arisaematis, Rhizoma Pinelliae, Semen Hyoscyami, Olibanum, Myrrha, Cortex Phellodendri, Radix Scutellariae, Rhizoma Coptidis, Indigo Naturalis, Radix Aconiti, Radix Aconiti Kusnezoffii, Radix Glycyrrhizae, a little tea, Semen phaseoli radiati powder, each equivalent of Calamina.
Method for making: above 18 flavors of pharmacy oil, except that Semen phaseoli radiati powder was standby, 17 flavor coarse pulverizations such as all the other Radixs Angelicae Dahuricae, Radix Arnebiae (Radix Lithospermi) were put in purified Oleum Gossypii semen or the Oleum Sesami and were soaked 24 hours, endured to medicine is withered with slow fire and floated for degree, filtered clean medicinal residues, promptly got medicine oil.Use pharmaceutical grade activated carbon decolorizing element then.
Write out a prescription 2.: above-mentioned medicine oil 192g, Semen phaseoli radiati powder 57.6g, Borneolum Syntheticum 6g, Cera Chinensis 7.2g, anhydrous lanolin 2.4g, Cera Flava 7.2g, jasmin essence 0.18g, white vaseline 12g.
Method for making: above eight flavors, Semen phaseoli radiati powder system micropowder is crossed 120 mesh sieves, the Borneolum Syntheticum porphyrize, above-mentioned depigmentation agents oil is heated to more than 100 ℃, and fine straining is put in the container, and insulation is placed, Cera Flava, Cera Chinensis are heated to 100 ℃, add white vaseline and anhydrous lanolin, after the fusing, filter, make substrate, get substrate 30g heating and melting, add above-mentioned depigmentation agents oil and stir evenly, put and be chilled to 70 ℃, add above-mentioned Semen phaseoli radiati powder, stirring and evenly mixing is cooled to 50 ℃, add Borneolum Syntheticum and jasmin essence, stir evenly, promptly.
Esophageal carcinoma blocks alleviates containing sugar-tablet
Prescription: Pseudobulbus Cremastrae Seu Pleiones, Galla Chinensis 60g, Semen Euphorbiae 30g, Moschus, each 9g of Realgar, Sal Ammoniacus, each 7g of Calculus Bovis, Knoxia valerianoides 45g, an amount of Oleum sesami, syrup.
Preparation method: Sal Ammoniacus is put into porcelain pulverization (keeping away metal), adds water boil, filters extracting juice, with vinegar (500g juice adds 500g vinegar), fries in shallow oil again, until boiling dry, gets the lark crystalline powder.
More than eight flavors, the Sal Ammoniacus crystallization is ground, Calculus Bovis, Realgar water fly; Moschus powder is broken into impalpable powder (above-mentioned medicated powder is crossed 100 mesh sieves), and four flavors such as all the other Pseudobulbus Cremastrae Seu Pleioness decoct with water 2 times, each 2h; merge and boil liquid, filter, filtrate is condensed into thick paste; it is an amount of to add Calculus Bovis, Sal Ammoniacus, Realgar, Moschus powder and concentration and be 50%~70% syrup; the system granule, drying, mixing; spray adds that correctives---slow fire burns to 8 sophisticated Oleum sesami, is pressed into and sucks sugar-tablet then.
Three plerosis side's complex capsules
Write out a prescription 1.: Radix Ginseng, each 8g of Cortex Cinnamomi, Rhizoma Chuanxiong 5g, Radix Rehmanniae Preparata 15g, Poria 8g, Rhizoma Atractylodis Macrocephalae preparata 10g, Radix Glycyrrhizae Preparata 5g, Radix Astragali 15g, Radix Angelicae Sinensis 10g, Radix Paeoniae Alba 8g.(directly making granule)
Method for making: above ten flavors, Cortex Cinnamomi, Rhizoma Chuanxiong, Radix Angelicae Sinensis extract volatile oil, and the aqueous solution after distillation device is in addition collected, medicinal residues and all the other seven flavors decoct with water secondary, each 2h, collecting decoction, filter, the aqueous solution after filtrate and the distillation merges, and is concentrated into 1/2 of original volume, add 3 times of amount 95% ethanol, the limit edged stirs, and 24h is placed in cold preservation, remove by filter precipitate, reclaim ethanol, add alcohol equally and handle, repeat 1 time, cleaner liquid is condensed into thick paste, add starch and ethanol and make granule, drying, granulate in right amount, cross 40 mesh sieves, granule sprays volatile oil such as adding Cortex Cinnamomi again, mixing, promptly.
Write out a prescription 2.: maljoe, Seem Lablab Album phytohemagglutinin (PHA) 50mg, saikoside D and each 40mg of Radix Bupleuri polysaccharide, polyporusum bellatus 40mg.
1. the extracting method of maljoe, Seem Lablab Album phytohemagglutinin (PHA)
Semen Canavaliae peeling, the porphyrize powder, with ethanol and ether defatting, drying, porphyrize powder again after adding 5 times of amount 0.2% sodium hydroxide and stirring, adds dilute hydrochloric acid and transfers PH to 6.8, and refrigerator (4 ℃) standing over night is centrifugal, the reject precipitation, the leaching supernatant is with the G200 gel chromatography.The upper column quantity stock solution of supernatant is 0.5%~1% (V/V) flow velocity 5ml/30 minute of gel column volume, at room temperature carries out, and collects with the segmentation automatic collector, and every pipe 5ml detects with the hemagglutination method, and its PHA is among 20~40 pipes.Merge the solution of 20~40 pipes, drain, promptly get pure product PHA with frozen vacuum dryer.The conjugate of this strain protein and polysaccharide, i.e. glycoprotein.
2. the extracting method of polyporusum bellatus
1. extract: go earth to make fragment the 50kg Polyporus, add the hot pressing of 5 times of amount distilled water and extract 3 times for 115.5 ℃, each time was respectively 1.5,1,0.5 hours, merged 3 times filtrate, removed insoluble impurities, got extracting solution.
2. concentrate, precipitate: said extracted liquid is evaporated to 5L, under agitation adds ethanol, makes pure content reach 80%, leaves standstill 12 hours, filters the collecting precipitation cold drying.Again dry thing is dissolved in the 3L distilled water, after the heated and boiled, filtering insoluble matter while hot, filtrate under agitation adds ethanol and reaches 80% concentration, leaves standstill 24 hours, filter, collecting precipitation, with washing with alcohol 3 times, cold drying, semifinished product, yield about 0.65%.
3. foreigh protein removing, decolouring, precipitation:
Crude product is dissolved in the 3L distilled water, accurately measure 30ml, under agitation drip 1% tannic acid (medicinal specification) solution, the limit edged heats up, and boils the centrifugal precipitation that discards in back, add 1 haze-free ending of tannic acid liquid to getting supernatant, converse crude product liquid and need add the amount of tannic acid liquid,, under agitation add 1% tannic acid liquid lentamente earlier with crude product liquid heated and boiled, after question response is complete, continued to boil 15 minutes, the active carbon of adding 2% stirred 10 minutes, filtered with buchner funnel, filtrate adds concentration of alcohol and reaches 70%, after leaving standstill 24 hours, filter, precipitate with 70% ethanol cyclic washing, till not having tannic acid to washing liquid, the wet product of precipitate.
4. absorption, eluting, precipitation, drying:
The product of wetting are dissolved in 2L, in 20% the hot ethanol, by placing the 2kg neutral alumina layer of buchner funnel, decompression is slightly slowly flowed out, and continues the hot distilled water eluting of adding 60%, collect the effluent concentrating under reduced pressure and become 2.5L, add concentration and reach 70% ethanol, place and promptly separate out white flocculent deposit, filter, collect, precipitation, low temperature or lyophilization promptly get the pure product of polyporusum bellatus.
3. the extraction therapy of saikoside D and Radix Bupleuri polysaccharide
The Radix Bupleuri coarse pulverization with methanol room temperature lixiviate 3 days, is reclaimed methanol, and residue is dissolved in weak ammonia, chloroform extraction, and the residue behind the recovery chloroform is dissolved in 90% methanol, with defat with petroleum ether, reclaims methanol and gets Radix Bupleuri soap D.
Radix Bupleuri medicinal residues after the methanol lixiviate extract the Radix Bupleuri polysaccharide according to the extraction step of above-mentioned polyporusum bellatus.
The 2. particulate preparation method of enteric-coated microcapsule of writing out a prescription
Method for making:
(1) dissolving is with 50mg, and maljoe phytohemagglutinin (PHA) and saikoside D and each 40mg of Radix Bupleuri polysaccharide and polyporusum bellatus 40mg are dissolved in an amount of 0.9%Nacl solution, stir evenly, and make concentrated solution.
(2) parcel moves to above-mentioned lysate in 3%~5% the gelatin solution, fully stir, it is an amount of under agitation to add water then, put in the water-bath and to keep 50 ℃, continue to stir, add 10% acetum, regulate PH3.5~3.6, at test under microscope, must proof produce agglutination, and see complete spheroidal microcapsule.
(3) being solidificated in above-mentioned microcapsule forms in the liquid, the formalin of adding 37%, continue to stir and further cooling, and it is an amount of to add cold distilled water, adds the frozen water cooling at reactor, makes microcapsule form liquid and reduces to 3~5 ℃, continuous stirring, behind about 1h, reuse 20% sodium hydroxide solution is adjusted PH8~9, and the network structure hole of gel is dwindled.
(4) after dispersion continues to stir 0.5h, add 10% and give birth to the starch slurry suspension, starch is fully scattered, formation one sealing coat is kept below 10 ℃ restir 1~2h between microcapsule.
(5) dry with the above-mentioned microcapsule of making, suction strainer separates, washing, eliminates moisture content as far as possible, and with 40 mesh sieve system granules, the starch that progressively adds dry (60 ℃ of dry 3h) in the granule is an amount of, makes loose particles, after one time 40 mesh sieve, and 60 ℃ of dry 2h.
(6) enteric coated Cellulose Acetate Phthalate (CAP) is made into 6% anhydrous propanone solution, get its 6 parts with 20% Lac, 1 part of mixing of ethanol solution, evenly, promptly make enteric coating solution, use air suspension coating machine that above-mentioned microcapsule granule is enteric coated then, promptly.
The preparation of three plerosis side's complex capsules
Method for making: will write out a prescription the 1. granule and the 2. enteric-coated microcapsule granule mixing of writing out a prescription, in the empty hard softgel shell of the certain specification of packing into, promptly.
XIAOLIU PIAN
Prescription 1: Rhizoma Bolbostematis, each 20g of Pseudobulbus Cremastrae Seu Pleiones, Semen Euphorbiae 15g, Fructus Aurantii 30g, Resina Toxicodendri (stir-fry) 6g, Oletum Trogopterori 15g, Radix Curcumae 18g, Alumen 18g, Herba Agrimoniae 18g, Sal Nitri 18g, Semen Strychni (processed) 12g.
The write out a prescription method for making of 1 extract
More than ten simply, Alumen, Sal Nitri levigation, Resina Toxicodendri, Oletum Trogopterori are pulverized.Seven flavors such as all the other Rhizoma Bolbostematiss decoct with water secondary, every 2h, and merging filtrate is condensed into thick paste.Add Resina Toxicodendri, Oletum Trogopterori fine powder and 2 the appropriate amount of starch of writing out a prescription, fully suction, and then Alumen, Sal Nitri powder added mixing, make granule, drying.
Prescription 2: 1 extract 1750g, starch 250g, magnesium stearate 100g write out a prescription.
The method for making of prescription 2
Take by weighing above-mentioned prescription 1 granule 1750g, add remaining starch, be ground into 14 order granules, add the magnesium stearate mixing, tabletting is used the Indigo Naturalis coating, every heavy 0.2g.
Town's cancer pain rubber plaster
The preparation of Chinese medicine condensed cream
Prescription: Bufo siccus (doing all), Semen Strychni 20g, a Flos Carthami 30g, Rhizoma Curcumae Longae, Cinnabaris, each 15g of Olibanum, Moschus 2g, Mentholum 30g, Herba Aristolochiae 30g, Radix Ilicis Pubescentis, each 15g of Sanguis Draxonis.
Method for making: above ten simply, and Cinnabaris, Moschus, Mentholum grind impalpable powder, Olibanum, Sanguis Draxonis coarse pulverization, and Flos Carthami, Rhizoma Curcumae Longae, Radix Ilicis Pubescentis are extracted volatile oil, and the aqueous solution after distillation device is in addition collected, and medicinal residues and Semen Strychni, Herba Aristolochiae decoct with water secondary, each 1h.The Bufo siccus coarse pulverization, other fries in shallow oil, and decocts secondary, each 2h.Aqueous solution after merging all decocting liquids and distilling is when heating is concentrated into 2/3 volume, with the Olibanum of coarse pulverization, Sanguis Draxonis adds, and continues to be concentrated into 1/3 volume, filtered while hot, be chilled to room temperature, add 95% ethanol then in filtrate, the limit edged stirs, in solution, contain amount of alcohol and reach about 65%, left standstill 24 hours, get cleaner liquid, precipitation adds 65% ethanol, extracts once again, merges, cleaner liquid reclaims ethanol.Be the thick paste shape 60~70 ℃ of evaporation and concentration to filtrates,, add mixing, promptly volatile oil such as Cinnabaris, Moschus, Mentholum fine powder and Flos Carthami, Rhizoma Curcumae Longaes.
Town's cancer pain rubber plaster preparation
1. raw material pre-treatment: get raw rubber and clean, 50~60 ℃ of heat dryings or dry are cut into bulk with bale splitter, and Colophonium is removed impurity, pulverizes.
2. system rubber plaster
With niggerhead in machinery repeatedly roll compacting reticulate thin slice, be spread out in put on the wire gauze cold, make and eliminate static 18~24h, airtight being dipped in an amount of gasoline treats to stir evenly in the dislocation adhesive supplier after the swelling, gradation adds vaseline, lanoline, liquid paraffin, zinc oxide and Colophonium etc., and add an amount of above-mentioned Chinese medicine condensed cream, and stirring 9h, the cream that makes slurry moves into the creme filter, utilize the spiral loader that heavy-gravity creme was pressed 80 order copper wire screen clothes, elimination impurity.Creme is put on " plaster coating machine " and is coated with cream, cutting, and lid serves as a contrast, and is cut into the fritter of 8cm*8cm, in the plastic bag of packing into, promptly.
Hydroxyl, demethyl speckle insect destructive of the roots of seedlings amine sheet
1. the preparation of Cantharidin
(1) technology path
(acidify, extraction) (2) technical process 1, cantharidin preparation: by the cantharis coarse powder: concentrated hydrochloric acid: the charge ratio of acetone=1: 0.025: 5.5 feeds intake.Get dry coarse powder and add 0.025 times of concentrated hydrochloric acid, use the acetone extraction 48 hours of 3 times of amounts of coarse powder then, leaching acetone, 2.5 times of acetone extraction of residual pool reuse 48 hours filter, merge acetone extract, residual pool is washed 1 time with proper amount of acetone, merges, and concentrates to reclaim acetone, get dark concentrated grease, promptly have mass crystallization to separate out.Filter, the crystallization petroleum ether is removed pigment and Animal fat, and the washing with alcohol of reuse 95% gets the cantharidin crude product, fusing point 213 for several times---216 ℃, promptly get cantharidin with the acetone recrystallize.
The preparation of 2 hydroxyls, demethyl cantharidimide (1) technology path
Figure A0011784500112
(2) technical process hydroxyl, the preparation of demethyl cantharidimide
1. cantharidin adds rare HNO 3Oxidant is heated to 150-160 ℃, is forced into the 10-15 atmospheric pressure and carries out oxidation reaction, makes the methyl (CH on the side chain 3) be oxidized to carboxyl (CooH).
2. add soda lime NaoH-CaO, heat is carried out decarboxylic reaction altogether, sloughs the carboxyl (CooH) on the side chain, promptly gets cantharidin.
3. feed ammonia (NH 3), pressurization, heating (200 ℃) utilizes the Gabriel synthetic method, synthetic pure primary amine (NH), product has water (H 2O) generate.
4. feed chlorine (Cl 2), irradiation carries out chlorination reaction, and with the H on the Cl atom replacement primary amine groups (NH), product has Hcl to generate.
5. add the NaoH aqueous solution, be hydrolyzed, promptly get hydroxyl demethyl cantharidimide.
3, hydroxyl, the preparation of removing basic cantharidimide tablet
By 100,000 calculating of preparation, need with hydroxyl, demethyl cantharidimide 25g-30g, starch 2kg, Pseudobulbus Bletillae (Rhizoma Bletillae) powder 5kg, magnesium trisilicate 1kg, aluminium hydroxide 2kg, 35% ethanol 9-10kg, magnesium stearate 0.1kg.
Get hydroxyl, demethyl speckle insect destructive of the roots of seedlings amine and starch and place ball mill, ground 24 hours, cross 100 mesh sieves, add Pseudobulbus Bletillae (Rhizoma Bletillae) powder, aluminium hydroxide and magnesium trisilicate, mix, by 40 mesh sieves, mix homogeneously, add 35% ethanol and stir the moistening soft material of making, cross 14 mesh sieves and granulate drying.Again dried granule is added magnesium stearate, after mixing a little, cross 14 order ferrum sieve granulate, abundant again mix homogeneously is stored in the metal bucket that is lined with cloth bag, the chemical examination of weighing, qualified back tabletting.Every hydroxyl, demethyl speckle insect destructive of the roots of seedlings amine 0.25g~0.3g, the heavy 0.101g of sheet.
The helexin sheet
1. the preparation of oleanolic acid
With little SHELIAN, the fruit of the Fructus Ligustri Lucidi of Oleaceae extracted 24 hours with 95% ethanol room temperature, tell filtrate, again with 95% fresh alcohol reflux 2 times (each 6 hours), merge extractive liquid,, concentrating under reduced pressure gets solid residue, be dissolved in the ethanol, transfer PH to 1, separate out crystallization, washing promptly gets the higher oleanolic acid of purity.
2. the preparation of anethole
The coarse pulverization gamin seed is packed in the enamel reactor, add 95% ethanol of Fructus Foeniculi powder weight 1~2 times (weight/volume), added extraction heat 2~3 hours, 75~80 ℃ of heating-up temperatures.Extraction finishes, and filters out filtrate, and filtering residue is pressed extraction procedures extraction 2~3 times again.Merging filtrate, and filtrate is drawn in the alembic, adding thermal distillation, vapo(u)rizing temperature is controlled between 80~85 ℃, reclaims ethanol, under this temperature conditions, till no longer including distillation.Residual fraction after the distillation is the mixture of Oleum Anisi Stellati and water.Through oil-water separation, discard water, promptly get and concentrate Oleum Anisi Stellati.
Get concentrated Oleum Anisi Stellati and add 95% ethanol of 3 times of amounts and 20% medicinal carbon, heating in water bath refluxed 30 minutes, filtered while hot, filtrate cooling, move to stirred crystallization in the ice bath again, drain,, drain again with the small amount of ethanol washing, place 50~60 ℃, drying promptly gets anethole.
3. the preparation of helexin
The dry Caulis Hederae Sinensis stem and leaf and the fruit of coarse pulverization are used methanol room temperature lixiviate 3 days, reclaim methanol, residue is dissolved in weak ammonia, chloroform extraction, and the residue behind the recovery chloroform is dissolved in 90% methanol, with the oil defat, reclaims methanol, promptly gets helexin.
4. ginsenoside's preparation
Extracting method is identical with the preparation method of helexin.Raw material adopts the raw hide Radix Ginseng.
Preparation: by 10,000 calculating of preparation, need with helexin 25g, oleanolic acid 500g, ginsenoside 1000g, anethole 3000g, starch 0.5kg, tapioca starch 2kg, stearic acid sodium sulfonate 0.35kg, magnesium carbonate 0.6kg, magnesium stearate 0.1kg, every contains helexin 2.5mg, and heavy every of theoretical sheet is 0.8g.
Get anethole and magnesium carbonate places ball mill, grind, make the abundant oil suction of magnesium carbonate.Other gets helexin, ginsenoside, oleanolic acid, starch and packs in the ball mill, grinds 24 hours.Two parts of grounds travel are mixed, and cross 100 mesh sieves, add tapioca starch, and the stearic acid sodium sulfonate mixes, and by 40 mesh sieves, mix homogeneously adds 35% ethanol and stirs the moistening soft material of making, and crosses 14 mesh sieves and granulates drying.Again dried granule is added magnesium stearate, after mixing a little, cross 14 order ferrum sieve granulate, abundant again mix homogeneously.Through weighing, chemical examination, qualified after, tabletting.
The photosensitizer part
One, the preparation of magnetic blood quinoline methyl ether (HMME) intravenous fluid
1.3, the preparation of 8--two (1-bromoethyl) deuteroporphyrin IX (DBD)
Removing the fibrosis Sanguis sus domestica by fresh anticoagulant is basic material through the chlorhematin that the digestion of the saturated acetic acid of Nacl makes, under the room temperature in acetic acid with dry HBr low pressure addition de-iron after, promptly make 3,8--two (1-bromoethyl) deuteroporphyrin IX (DBD).
2. the preparation of blood quinoline methyl ether (HMME)
200ml 3,8--two (1-bromoethyl) deuteroporphyrin IX two hydrobromate glacial acetic acid saturated solutions stir following to the mixed liquid of 360mml methanol and 1440ml water, stirring reaction 2~3h, reactant liquor adds acetic acid then and regulates PH to 4~5 with 10mol/L NaoH hydrolysis, the precipitate that the filter collection is separated out, wash 3 times, blot, drying under reduced pressure gets the aubergine solid, and the latter carries out silica gel column chromatography with chloroform cHcl 3--methanol cH 3OH--formic acid HcooH (10: 1: 0.1) eluting,--(1-methoxy ethyl)--8 (or 3)--(1-ethoxy) deuteroporphyrin IX is hematoporphyrin monomethyl ether (HMME) 590mg to get 3 (or 8).
3. prepare the lysate of blood quinoline methyl ether (HMME)
Be adjusted to PH=7 with in 0.5ml, 0.1N, NaoH, stirring 1h solution under the 10mgHMME room temperature with hydrochloric acid, stir evenly, promptly get the lysate of blood quinoline methyl ether (HMME).
4. the preparation of magnetic HMME microcapsule
In 15 parts of benzole solns that contains 10% polystyrene, add 3 parts of magnetic colloid solution (such as iron dextran colloid solution).
To make mean particle dia after the mulser emulsifying is the emulsion first time below the 0.5um; under constantly stirring; emulsion for the first time joined 70 parts the gelatin that contains; polyvinyl alcohol and surfactant are (as nonionic surfactant; Tween 80 and sorbester p17 share); make it in the aqueous solution of protecting colloid material to disperse; produce emulsion for the second time; while stirring temperature is brought up to 35~40 ℃; be incubated a few hours, decompression, drying; remove the semipermeable membrane that solvent forms polymer, promptly make the aqueous solution that contains semi-finished product magnetic microcapsule.
A small amount of blood quinoline methyl ether (HMME) lysate (this amount is determined accurate dosage by later test data) joined 30 parts the gelatin that contains; polyvinyl alcohol and surfactant; Tween 80 and sorbester p17 share; in the aqueous solution of protecting colloid material; abundant mixing; then above-mentioned half-finished magnetic microcapsule aqueous solution is added; while stirring temperature is brought up to 35~40 ℃; be incubated a few hours; drying under reduced pressure; remove semi-transparent film and impurity that solvent forms polymer, promptly make the aqueous solution that contains the HMME microcapsule that is magnetic.Require particle diameter below 1um, also there is a small amount of pore structure on magnetic HMME microcapsule surface, still possesses the physical absorption function, and above-mentioned preparation water uses water for injection.
5. the preparation of magnetic blood quinoline methyl ether (HMME) intravenous fluid
Under the lucifuge condition, with aseptic, under purified blood quinoline methyl ether (HMME) the 10mg room temperature in 0.5ml, 0.1N, stir 1h among the NaoH, solution is adjusted to PH7 with hydrochloric acid, and add an amount of water for injection, to contain the 0.1mg that has an appointment (this amount is determined accurate dosage by later test data) sterilization then, pure magnetic HMME microcapsule aqueous solution adds, be incubated 37 ℃, fully stir, and add an amount of fabaceous lecithin emulsifying agent, transfer PH to 7.4 with 10% natrium carbonicum calcinatum then, and add Nacl and regulate in right amount etc. and to ooze, add adding to the full amount of water for injection, fine straining, embedding is pressure sterilizing in the lucifuge ampoule, promptly gets used for intravenous injection magnetic HMME Emulsion.
Two, the preparation of monoclonal antibody blood quinoline methyl ether (HMME) intravenous fluid
1, blood quinoline methyl ether (HMME) and human serum albumin's (HSA) fusion
(1) human serum albumin's (HSA) dissolving
Lyophilizing human serum albumin (HSA) joined in an amount of 0.9% the sodium chloride normal saline, stir evenly, promptly get human serum albumin's lysate.
(2) dissolving of blood quinoline methyl ether (HMME) will be stirred 1h under the 10mg HMME room temperature in 0.5ml, 0.1N, NaOH, and solution is adjusted to PH=7 with hydrochloric acid, stirs evenly, and promptly gets the lysate of blood quinoline methyl ether (HMME).
(3) fusion of HMME and HSA
A little human serum albumin (HSA) lysate (determining accurate dosage by later test data) is joined in blood quinoline methyl ether (HMME) lysate, be incubated 37 ℃, stir, leave standstill, filter, promptly get the natural fusion liquid of HMME and HSA.
2, conjugate monoclonal antibody-HMME-HSA's is synthetic
Hydroxyl on the terminal leucine of the epsilon-amino of lysine side-chain in the monoclonal antibody molecule and succinyl tetrapeptide is generated amido link to link to each other, again with the other end and the HMME-HSA coupling of succinyl tetrapeptide arm, form conjugate, coupling reaction occurs in the free amine group of lysine on the HMME-HSA complex albumin and the carboxyl of succinic acid forms amido link (See Figure)
Figure A0011784500141
3, the preparation of monoclonal antibody HMME--HSA intravenous fluid
With aseptic purified monoclonal antibody HMME-HSA conjugate solution, transfer PH to 7.4 with 10% natrium carbonicum calcinatum, and add Nacl and regulate in right amount etc. and to ooze, add and add to the full amount of water for injection, use sintered glass filter aseptic filtration, under aseptic technique, embedding in the lucifuge ampoule promptly.
Three, the preparation of ferritin blood quinoline methyl ether (HMME) intravenous fluid
1. the preparation of hemoglobin
1. extract erythrocyte and collect healthy people's blood or Placenta Hominis, puerperal 10 liters of blood or directly utilize the preparation serum gamma globulin of human placenta--the dipping extraction process, the erythrocyte of reject under agitation adds its volume 10% concentration and is 2.5% sodium citrate solution anticoagulant, stir, leave standstill, make the erythrocyte natural subsidence, remove the most of blood plasma in upper strata, centrifugal again all the other blood plasma that eliminate of subnatant, the sodium chloride that adds 3 times of amounts 0.9% again, washed twice, the centrifugal overstocked erythrocyte (about 4 liters) of collecting.
2. cell breakage
The erythrocyte that extracts is refrigerated to subzero 15 ℃~20 ℃, makes it to solidify, dissolving lentamente then, so repeatable operation is all broken until erythrocyte.
3. extract hemoglobin
0.4 kilogram of refining sodium chloride (Nacl) joined fully dissolve in 10 liters the distilled water and join then in the broken red blood cell liquid that has returned to room temperature (20 ℃), stir, leave standstill, filter, collect the hemoglobin precipitation of separating out, add sodium chloride in the filtrate again, repetitive operation is repeatedly all separated out until hemoglobin.
4. hemoglobin is refining
With the hemoglobin dialysis desalting of collecting, the desalination hemoglobin adds appropriate amount of deionized water (pure water), stir evenly, and add equivalent acetone, (0-4 ℃) left standstill 4~6 hours under the low temperature, centrifugal collecting precipitation, repetitive operation once after precipitation is used the pure water washes clean, is dewatered twice with dehydrated alcohol, vacuum drying promptly gets the pure product of hemoglobin.
5. the dissolving of hemoglobin
The pure product of hemoglobin are joined in an amount of 0.9% the sodium chloride normal saline, stir evenly, promptly get hemoglobin solutions.
2. hemoglobin and blood quinoline methyl ether (HMME) merge under physiological condition
Under the lucifuge condition, a little hemoglobin lysate (determining accurate dosage by later test data) is joined in the blood quinoline methyl ether solution (aforementioned), be incubated 37 ℃, stir 1h, leave standstill, filter, promptly get the fusion liquid of hemoglobin (ferritin) and blood quinoline methyl ether.
3. the preparation of ferritin blood quinoline methyl ether (HMME) intravenous fluid
Under the lucifuge condition, aseptic, purified above-mentioned ferritin and HMME are merged liquid, add an amount of water for injection, transfer PH to 7.4 with 10% natrium carbonicum calcinatum then, and add Nacl and regulate in right amount etc. and to ooze, add adding to the full amount of water for injection, use sintered glass filter, under the aseptic filtration operating condition, embedding is in the lucifuge ampoule, promptly.
Biochemical medicine part
Cancer cachexia is alleviated the preparation of quiet dropping liquid
1. tryptic preparation
With the Pancreas caprae seu ovis is the extraction method of raw material
(1) technology path
(extraction) (segmentation is saltoutd)
H 2SO 4(NH 4) 2SO 4→ precipitate spends the night Pancreas caprae seu ovis--→ extracting solution----
Figure A0011784500161
(2) technical process
1. extract: the fresh or bright Pancreas caprae seu ovis that freezes, peel off fat and connective tissue, rub, every 10kg pancreas slurry adds 0.1mol/L sulfuric acid solution (the 116ml commercial sulphuric acid adds water to 20kg) 20kg, stirs after 1~2 hour, and placement is spent the night.Adding 3.52kg industrial sulphuric acid ammonium gradually next day under constantly stirring, concentration reaches 0.3 saturation, adds in about 1 hour, and all dissolving was placed 3~5 hours again, filter extracting solution.In case of necessity, filtering residue can be used 10L, and the 0.1mol/L sulfuric acid solution extracts 1 time again.
2. segmentation is saltoutd: every 10L extracting solution adds industrial sulphuric acid ammonium 2.73kg under constantly stirring, and adds in 1~2 hour, reaches 0.7 saturation, and placement is spent the night.Inhale next day and go the supernatant (can supply to extract ribonuclease), filter, get the 430g filter cake.Filter cake calculates the ammonium sulfate (CP) that adds 176g/L by lysate and reaches 0.7 saturation with 4 times of amount volume dissolved in distilled water, and placement is spent the night.Next day, decompressing and extracting is collected filter cake.Every 10kg pancreas gets the 300g filter cake approximately.
3. dialysis, crystallization: get the 300g filter cake and add 0.4mol/L, the borate buffer of PH9 (49.4g boric acid is dissolved in the distilled water, adds 80ml, 5mol/L sodium hydroxide or 16g solid sodium hydroxide, with distilled water diluting to 1L, PH9~10.When mixing with saturated magnesium sulfate, pH value can reduce, and therefore, PH needn't be transferred to 9.1 times of adding distil water dilution, be the 0.4mol/L borate buffer) 200ml dissolving, remove by filter insoluble matter, add 200ml " crystallization dialysis solution " (get the 0.4mol/L borate buffer and saturated magnesium sulfate equal-volume mixes, PH is lower than at 8 o'clock, drips gradually with saturated potassium carbonate and transfers to PH8) again, pack in the bag filter, in the time of 0~5 ℃, " crystallization dialysis solution " dialysed, changed once in per 24 hours " crystallization dialysis solution ", begin to occur crystallization after 3~4 days in the bag filter, about one all crystallizations are complete.
4. recrystallize, drying: the bag taking intercrystalline filters with buchner funnel, approximately the crystallization of 22g trypsin, the same operation recrystallize 1 time approximately 18g.Crystallization is dissolved among 0.01mol/L hydrochloric acid (the 8ml hydrochloric acid adding distil water 10L) 100ml, dialyses in 0.01mol/L hydrochloric acid and desalts, and lyophilization gets injection crystallization Pancreas caprae seu ovis protease.Yield is 0.6g/kg, enzyme activity 150 units/and more than the milligram.
2. the preparation of lysozyme
(1) technology path (absorption) (foreigh protein removing) 724 resin water, phosphate buffer--------→-→-------------→ 0~5 ℃ of PH6.5 of adsorbate Ovum Gallus domesticus album (eluting) (precipitation) (dialysis), 10% (NH 4) 2SO 440% (NH 4) 2SO 4Distilled water------------------→ eluent----------------→ crude product--------------→
Divide 4 dissolvings
(saltouing) (drying)
NaoH, Hcl, Nacl acetone dialysis solution--------------→ wet lysozyme----------→ first PH8.5~9, back PH3., 50 ℃ (chromatography)
The DEAE--C lysozyme-------→ injection lysozyme purification
(2) technical process
1. raw material is handled: fresh or freezing Ovum Gallus domesticus album 70kg, and to survey PH with reagent paper and should be about 8, the copper that thawed sieve is removed the umbilical cord in the Ovum Gallus domesticus album, eggshell fragments and other impurity.
2. absorption: temperature drops to about 5 ℃, adds the 724 resin 10kg (weight in wet base) that handle well in stirring resin all is suspended in the Ovum Gallus domesticus album, remains on 0~5 ℃, and stirring and adsorbing 5 hours moves into Ovum Gallus domesticus album 0~5 ℃ in freezer again, and is static, spends the night.
3. foreigh protein removing, eluting, precipitation: the supernatant is inclined to gradually, and the protein that lower-layer resin is adhered to the clear water flush away is washed 4 times repeatedly, notices preventing that resin runs off the part of at last the resin sucking filtration being anhydrated.Other gets PH6.5,0, and 15mol/L phosphate buffer 24L divides to add for 3 times in the resin, stir about 15 minutes, each back decompress filter branch that anhydrates that stirs.Reuse 10% ammonium sulfate 18L divides 4 times the eluting lysozyme, stirs half an hour at every turn, and filtration is drained.The merging eluent adds 32% (W/V) solid ammonium sulfate by cumulative volume and makes content reach 40% concentration, and the adularescent precipitation produces, and place and spends the night at cold place, the siphon supernatant, and precipitation and centrifugal separation or sucking filtration get crude product.
4. dialysis: crude product adding distil water 1.5kg is made it dissolving, and the bag filter of packing in the freezer, was dialysed 24~36 hours, removed most of ammonium sulfate, got dialysis solution.
5. saltout: will clarify dialysis solution, slowly drip the 1mol/L sodium hydroxide, constantly stir simultaneously, pH value rises at 8.5~9 o'clock, if any white precipitate, should centrifugally immediately remove, in stirring, add 3mol/L hydrochloric acid then, make solution PH reach 3.5, by volume slowly add 5% solid sodium chloride, be that adularescent precipitation is separated out, placed 48 hours at 0~5 ℃ of freezer, centrifugal or filter the lysozyme precipitation.
6. dry: precipitation adds 10 times of amounts and is chilled to 0 ℃ anhydrous propanone, constantly stirs, and makes the granule pine thin, and a few hours are left standstill at cold place, and with funnel elimination acetone, precipitation is used vacuum drying, till no acetone stink, promptly gets oral or external lysozyme raw material.
As without the acetone dehydration, can dialyse, its dialysis solution lyophilization gets the not lysozyme goods of sodium chloride-containing.Yield is calculated as 2.5% by Ovum Gallus domesticus album weight.
7. DEAE--C chromatography, purification: the crystallization lysozyme of sodium chloride-containing is not dissolved in the PH4.6 aqueous acetic acid, transfer the centrifugal precipitation of removing of PH8.5, clear liquid passes through 0.01mol/L, the DEAE-C post that PH8.5 phosphate buffer balance is crossed, suitably the control flow velocity is collected effluent, transfers PH5.5, lyophilizing, the response rate nearly 100%.Promptly get highly purified injection lysozyme.3. the preparation of papain (1) technology path
(squeezing) (absorption)
Sodium benzoate kaolin Fructus Chaenomelis------→ press juice-------→ adsorbate
10℃
(eluting) (saltouing sucking filtration) Na 2CO 3Or NaoH, (NH 4) 2SO 4Hcl, (NH 4) 2SO 4----------------------------------→ eluent------------------------------→
PH6.5~7 PH4.5~5
(dissolving) (stablizing)
Tap water, NaoH EDTA-2Na, SO 2, the Vc semifinished product--------------→ clear liquor-------------------------→
PH7~7.5
(absorption) (eluting)
Tannic acid Vc stabilizing solution--→ tannic acid adsorbate----→ eluent---
PH4.5 (drying is pulverized)-----→ finished product
(2) technical process
1. squeezing: Fructus Chaenomelis is extruded juice through squeezer, add 0.05% sodium benzoate by fruit juice and make antiseptic, the raw material storage low-temp storage of making a gift to someone is standby.
2. absorption, eluting: press fruit for cider and put in the stainless steel cold wall tank, constantly stir, rotating speed 40~60r/min adds 4% kaolin of juice amount, in 10 ℃ of absorption 15~20 minutes, standing over night.Inferior kaolin sedimentation in morning is good, and supernatant is removed in siphon, stays wet potter's clay, add sodium carbonate saturated solution or 6.6% hydrochlorinate sodium and regulate PH6.5~7, add ammonium sulfate or edible refined salt again, stirred 25~30 minutes by wet soil 50%, carry out eluting, promptly carry out filter pressing with pressure filter.
3. saltout sucking filtration: pressing filtering liquid adds 9% hydrochloric acid (concentrated hydrochloric acid: water=1: 3) regulate PH4.5~5, add 20~25% ammonium sulfate (or 25% refined salt) again and saltout, stir gently with wooden stick, make the sodium sulfate dissolving, the seasoning freezer in steel drum.In inferior morning, siphon goes out the upper strata metabisulfite solution, and lower floor separates out rare enzyme and sticks with paste, and centrifugalize gets thick enzyme and sticks with paste.Remove the seasoning of part of sulfuric acid ammonium liquid in-20 ℃ through the buchner funnel sucking filtration, wait to make with extra care.
4. dissolving: get the tap water that the enzyme crude product adds 8~10 times of amounts, regulate PH7~7.5, be stirred to dissolving gently with 16% sodium hydroxide.Prevent foaming, filter pressing rapidly separates and removes impurity, gets clear liquor.Use a small amount of tap water flushing pipe and pressure filter at last, washing liquid and above-mentioned clear liquor merge.
5. stable, absorption: above-mentioned clear liquor, add 0.05% EDTA-2Na by the juice amount, 0.06% sulfur dioxide, 0.02% ascorbic acid used as stabilizers adds 0.4~0.6% tannic acid according to quantity and adsorbs after the stirring, must precipitate adsorbate.
6. eluting, drying: get the tannic acid adsorbate, with PH4.5 ascorbic acid solution eluting, filtration press dry, drying under reduced pressure, injection papain purification elaboration.
4. the preparation of trypsin papain lysozyme complex
Get 2% lysozyme soln 1000ml and act on mutually with 2% Trypsin solution 500ml and 2% papain solution 500ml, at PH4.5,4 ℃ kept 24 hours, and promptly separated out lysozyme papain trypsin complex.
With the lysozyme papain trypsin complex lyophilization of separating out, and add an amount of DL--threonine used as stabilizers, behind the mixing, in the vial of band plug and the aluminium lid of packing into, put in the refrigerator and preserve, can take out when preparing quiet dropping liquid.
5. the preparation of quiet dropping liquid
(1) with an amount of NaHco 3Pure product add the injection water and are mixed with 200ml, and the solution of PH7.4 is filtered to clarification with No. 4 sintered glass funnels, (preferably fills nitrogen) at 0.5kg/cm in the infusion bottle of the 250ml that packs into then 2Sterilized 30 minutes, and a collection ofly went out 100 bottles.
(2) with an amount of Na 2Co 3With the pure product of NaoH, press Naco 3: NaoH=3: 1, add the injection water and be mixed with 2 50ml, the solution of PH12 is filtered to clarification with No. 4 sintered glass funnels, (preferably fills nitrogen) at 0.5kg/cm in the infusion bottle of the 250ml that packs into then 2Sterilized 30 minutes.A collection ofly go out 1 bottle.
6. the preparation of quiet dropping liquid
Using " cancer cachexia is alleviated quiet dropping liquid " before, at first measuring the pH value of blood samples of patients, using " disposable syringe " to extract the NaHco of PH7.4 then with accurate PH meter (a kind of instrument of measuring the solution pH value) 3Transfusion 5ml injects the lyophilized formulations bottle that lysozyme papain trypsin complex is housed, and jolting is fully dissolved complex, changes a syringe then, takes out most complex lysate, injects the NaHco of PH7.4 3In the infusion bottle.According to the blood samples of patients pH value, extract (the Naco of PH12 with syringe 3+ NaoH) transfusion, the NaHco of injection PH7.4 3In the infusion bottle, transfer PH7.5~8.5, just can give patient's intravenous drip then with the PH meter.Cancer patient's blood pH is adjusted to about healthy people's PH7.4 as far as possible, and this infuses with joining with usefulness, must not shelve more than 1 hour at room temperature, in case the trypsin inactivation.This transfusion is preferably in and puts, chemotherapy intravenous drip in preceding 12 hours, once a day.But make sure to keep in mind to use " cancer cachexia is alleviated quiet dropping liquid " in the hemorrhage phase of cancer.
The quiet dropping liquid of polyinosini--Thymosin--Radix Isatidis
The preparation of Thymosin
1. process route
(smash to pieces, extract)
Rub normal saline porcine thymus--→ thymus fragment------→ extracting solution (component 1)
(precipitation) (heating foreigh protein removing) acetone------→ supernatant (component 2)--80 ℃ of → acetone powders (component 3), 10 ℃ of 15min
(2) technical process
(1) fresh or freezing porcine thymus is removed fat and rub after, add 3 times of amount normal saline, in tissue mashing machine, make homogenate, after 14000*g is centrifugal extracting solution (component 1).
(2) heating foreigh protein removing: 80 ℃ of heating of extracting solution 15min, to the thermally labile part, the centrifugal precipitation of removing gets supernatant (component 2) with precipitation.
(3) precipitation: supernatant is cooled to 4 ℃, adds-10 ℃ of acetone of 5 times of volumes, filters collecting precipitation, gets acetone powder (component 3) after the drying.
(4) segmentation is saltoutd: acetone powder is dissolved in the PH7.0 phosphate buffered solution, and adding ammonium sulfate to saturation is 0.25, and it is 4.0 that centrifugal removal precipitation is transferred PH to thermally labile part supernatant (component 4), and adding ammonium sulfate to saturation is 0.50, the thing of must saltouing.
(5) ultrafiltration: the thing of will saltouing is dissolved in the 10mmol/L Tris-Hcl buffer of PH8.0, and ultrafiltration is got molecular weight at the ultrafiltrate below 15000.
(6) desalination, drying: ultrafiltrate is after Sephadex G-25 desalination, and lyophilization gets thymosin (component 5).
The preparation of polyinosinic acid (polyinosini Poly I:C)
Production technology
1, substrate 5 '-preparation of nucleoside diphosphate pyridiniujm
5 '-nucleoside=phosphoric acid pyridiniujm (being the CDP pyridiniujm, the IDP pyridiniujm)
2, the preparation of immobilization polynucleotide phosphorylase.
(1) preparation of enzyme: Collect enzyme the highest part alive in the 0.35mol/LNacl eluent.
(2) preparation of solid phase carrier:
Figure A0011784500205
----------------→------ethyl sulfone aniline etherificate NaNo2+Hcl diazotising----------→--→--------------------------→ solid phase carrier
(3) immobilization polynucleotide phosphorylase is gone into carrier in the ice bath with the enzyme drop of separation and purification.Obtain covalently bound immobilization polynucleotide phosphorylase.
3.PoIy I:C preparation
(1) substrate pretreatment: the CDP pyridiniujm changes into lithium salts, and IDP changes into sodium salt.
(2) enzymatic reaction: (every milliliter of reactant liquor contains u mol/L number) IDP or CDP15; Tris 150; Mgcl2 6; EDTA1; Polymerase 5 units, PH9.0,37 ℃, 3-4 hour).Transfer PH1.5~2.0 with hydrochloric acid, make PoIyI (or PoIyC) precipitation, centrifugal immediately, after this in phosphate buffer, dissolve, mix with PoIyC Deng mole PoIyI, filter, filtrate is transferred PH1.5~2.0 with hydrochloric acid, is stirred to crystallization and separates out fully, be placed on crystallization below 10 ℃ 1 hour, refilter and collect crystallization absolute ethanol washing 3 times, drain 60 ℃ of vacuum dryings, promptly get PoIy I:C finished product.
The preparation of Radix Isatidis powder injection
With the Radix Isatidis coarse pulverization, get 1.5kg, heating decocts three times, and each 30 minutes, filter, merging filtrate is concentrated into 1500ml, adds doubling dose 95% ethanol, filters, and reclaims ethanol.To remain medicinal liquid and be concentrated into 700~1000ml in water-bath, the cooling back adds ether 250ml, discards ether after leaving standstill, and adds 2% gelatin solution of 2 times of amounts of medicinal liquid again, sucking filtration.Filtrate adds 2 times of amount 95% ethanol again, leaves standstill 24 hours, filters, and reclaims ethanol, is chilled to room temperature, filters, and the filtrate spray drying is made instant injectable powder.
The preparation of the quiet dropping liquid of polyinosini--Thymosin--Radix Isatidis
With Thymosin, the polyinosinic acid crystal powder mixes by 1: 1: 0.5 with the instant injectable powder of Radix Isatidis.And add an amount of mannitol used as stabilizers, after the mixing, in the vial of pack into band plug and aluminium lid.Before facing usefulness, use 250ml, the transfusion of 0.9% sodium chloride is made into quiet dropping liquid, with joining with usefulness.
Merging chemicotherapy dwindles the tumor body and carries out the used X-ray magnetic therapy machine of optical dynamic therapy and drug system treatment thereof the concrete using method greater than the above tumor body of 3cm*3cm.
After using following medicine 1h, 43 ℃ of the constant temperature of the most handy X-ray magnetic therapy machine pulsation Magnetotherapeutic apparatus (only opening the solenoid power supply, magnetic pole malleation cancer place) constant temperature, pulsation magnetic therapy 30min.(magnetic field intensity 4000GS~6000GS).
For the tumor body greater than the cancer patient more than the 3cm*3cm, 24h before chemicotherapy, first intravenous drip " cancer cachexia is alleviated quiet dropping liquid " is at interval taken the anti-compound recipe complex capsule in osmanthus behind the 6h.Under the situation of not using the X-ray magnetic therapy machine, carry out radiotherapy behind the 5h or take chemotherapeutics, 6h clothes XIAOLIU PIAN behind the chemicotherapy, clothes three plerosis side's complex capsules behind the 5h are obeyed hydroxyl again behind the 6h at interval, demethyl speckle insect destructive of the roots of seedlings amine sheet or clothes helexin sheet.24h after chemicotherapy, the quiet dropping liquid of intravenous drip polyinosini-Thymosin is further strengthened the therapeutic effect of aforementioned medicine.
Attention: at the chemicotherapy resting stage, not take the anti-compound recipe complex capsule in osmanthus for well, in addition, and in the carcino-matous hemorrhage phase, must not be with " cancer cachexia is alleviated quiet dropping liquid.The constant temperature pulsation Magnetotherapeutic apparatus of use X-ray magnetic smelting cancer machine carries out electric heating magnetic and rules by law thoroughly when treating, and asks one behind clothes cancer therapy drug 1h, carries out, and please not want separately or use in advance, makes sure to keep in mind.
To the patient of skin carcinoma, esophageal carcinoma, preferably using the bundle group medicine of osmanthus anti-food (skin) compound capsule simultaneously--skin carcinoma ointment for promoting muscle growth and esophageal carcinoma block alleviates containing sugar-tablet.When cancer pain was violent, pain spot sticked " town cancer pain rubber plaster ", and with the constant temperature pulsation Magnetotherapeutic apparatus of X-ray magnetic therapy machine, the positive pressure pain point of magnetic pole, the magnetic therapy of pulsing 1h can be alleviated B section cancer pain rapidly.
When utilizing the treatment of said medicine, apparatus to make the tumor body narrow down to less than 3cm*3cm, intravenous injection ferritin HMME or magnetic HMME Intravenous injection solution are behind the 1h, the constant temperature Magnetotherapeutic apparatus of X-ray magnetic therapy machine is opened, magnetic pole malleation cancer place, heated at constant temperature 1h, magnetic control location 2h.After stopping 2h, the silicon fiber of X-ray magnetic therapy machine is imported in the body cavity apart from tumor surface 3cm part by endoscope.Open the constant temperature Magnetotherapeutic apparatus of X-ray magnetic therapy machine simultaneously, the cancer district of magnetic pole malleation body surface, and open the X line, laser aid and connect the power supply of two metallic plates, the light dosage of control X-ray can carry out the tumor dynamic therapy and (PDT).
If intravenous injection monoclonal antibody HMME Intravenous injection solution when then carrying out photodynamic tumor treatment (PDT), without the constant temperature Magnetotherapeutic apparatus of X-ray magnetic therapy machine, is only used the X line, laser aid and charged particle accelerator.
When clinical treatment, can carry out repeatedly PDT or anti-according to tumor body size and biopsy situation with osmanthus, three plerosis side's complex capsules, XIAOLIU PIAN is carried out prognosis, in case recurrence.
Below in conjunction with accompanying drawing X-ray magnetic therapy machine of the present invention is described:
1. two of charged particle accelerator round-meshed metallic plates must be placed in the glass tube with vacuum.The cathode metal plate is placed on outside the solenoid, and the negative pole metallic plate is placed in the solenoid, apart from solenoid centre position 3~5cm.
2. pass the X ray of plane mirror and converge into a branch of hybrid circuit structure through the laser of flat mirror reflects, this hybrid circuit structure is after the electric field of charged particle accelerator quickens, and the aperture of being deployed in the middle of solenoid by special silicon fiber is derived again.This optical fiber special feature is that the outside of glass stamen line is a raw material with Indium sesquioxide., stannum oxide earlier, adopts the deielectric-coating of " Vacuum Coating method " plating one deck blocking-up electromagnetic wave path, and then wraps up the stamen line with " covering ".
3. the thermometer of thermostat is placed on the outside of spiral piping arrangement, and armature preferably is placed on solenoidal centre position.

Claims (15)

1, the X-ray magnetic therapy machine is that a kind of X line, laser, the three-in-one light power of constant temperature pulsation magnetic therapy are controlled the cancer medical apparatus and instruments.
It is characterized in that forming by the special silicon fiber of X-ray apparatus (1) laser device (2) charged particle accelerator (3) pulsation Magnetotherapeutic apparatus (4) thermostat (5) parts such as (6).
2, the anti-compound recipe complex capsule in osmanthus is a kind of chemicotherapy drug combination, and is the drug distribution modifying agent of photosensitizer in the tumor photodynamic therapy (PDT).
It is characterized in that directly making 40 order granules by basis side (1) Ramulus Cinnamomi, Poria, Cortex Moutan, Semen Persicae, each 9g of Radix Paeoniae, basis side (2) Herba Agrimoniae 10g, Herba Solani Lyrati 30g, Herba Solani Nigri 25g, Semen Arecae 15g, Rhizoma Pinelliae Preparata 10g, Radix Glycyrrhizae 5g system 40 order enteric-coated microcapsule granules, (1) square granule and (2) square enteric-coated microcapsule granule then, mixing, pack in the hard capsule case, be prepared into capsule.
3, according to claim 2, the skin carcinoma ointment for promoting muscle growth is the binding medicine of osmanthus anti-skin compound recipe complex capsule, is a kind of skin carcinoma coating externally-applied ointment.
It is characterized in that making ointment by the substrate of prescription (1) Radix Angelicae Dahuricae, Radix Arnebiae (Radix Lithospermi), Radix Angelicae Sinensis, Rhizoma Arisaematis, Rhizoma Pinelliae, Semen Hyoscyami, Olibanum, Myrrha, Cortex Phellodendri, Radix Scutellariae, Rhizoma Coptidis, Indigo Naturalis, Radix Aconiti, Radix Glycyrrhizae, catechu, Semen phaseoli radiati powder, each equivalent pharmacy oil of Calamina and prescription (2) Cera Chinensis 7.2g, Borneolum Syntheticum 6g, anhydrous lanolin 2.4g, prescription (1) medicine oil 192g, Semen phaseoli radiati powder 57.6g, Cera Flava 7.2g, jasmin essence 0.18g, white vaseline 12g.
4, according to claim 2, it is the binding medicine of anti-relapse due to improper diet side, osmanthus complex capsule that esophageal carcinoma blocks containing of alleviation sugar-tablet, is that a kind of esophageal carcinoma blocks alleviation holding in the mouth for dissolving drug sugar-tablet.
It is characterized in that by prescription: Pseudobulbus Cremastrae Seu Pleiones, each 60g of Galla Chinensis, Knoxia valerianoides 45g, Moschus, each 9g of Realgar, Semen Euphorbiae 30g, Sal Ammoniacus, each 7g of Calculus Bovis, Oleum sesami, syrup are pressed into the holding in the mouth for dissolving drug sugar-tablet in right amount.
5, three plerosis side's complex capsules are a kind of chemicotherapy supports, improving agent.
It is characterized in that directly making 40 order granules by prescription (1) Radix Rehmanniae Preparata 15g, Poria 8g, Radix Paeoniae Alba 8g, Radix Astragali 15g, Radix Ginseng 8g, Radix Angelicae Sinensis 10g, Cortex Cinnamomi 8g, Radix Glycyrrhizae Preparata 5g, Rhizoma Chuanxiong 5g, Rhizoma Atractylodis Macrocephalae preparata 10g; prescription (2) maljoe; Seem Lablab Album phytohemagglutinin (PHA) 50mg, saikoside D and each 40mg of Radix Bupleuri polysaccharide; Grifola umbellata polysaccharide 40mg system 40 order enteric-coated microcapsule granules; prescription (1) granule and prescription (2) enteric-coated microcapsule granule mixing then; pack in the hard capsule, be prepared into capsule.
6, XIAOLIU PIAN is a kind of chemicotherapy drug combination, use simultaneously with chemicotherapy, but the potentiation chemicotherapy, and the effect that prevents eliminating side effect of radiotherapy and chemotherapy to is arranged.
It is characterized in that making condensed cream by prescription (1) Fructus Aurantii 30g, Rhizoma Bolbostematis 20g, Oletum Trogopterori 15g, Herba Agrimoniae 18g, Resina Toxicodendri (stir-fry) 6g, Pseudobulbus Cremastrae Seu Pleiones 20g, Radix Curcumae 18g, Alumen 18g, Sal Nitri 18g, Semen Strychni (processed) 12g, Semen Euphorbiae 15g, prescription (2) magnesium stearate 100g prescription (1) condensed cream 1750g, starch 250g elder brother expect tabletting, use the Indigo Naturalis coating.
7, town's cancer pain rubber plaster is that a kind of pain spot sticks and uses the chemicotherapy support, the auxilliary product for the treatment of.
It is characterized in that by prescription: Bufo siccus (doing all), a Flos Carthami 30g, Rhizoma Curcumae Longae, Cinnabaris, each 15g of Olibanum, Semen Strychni 20g, Moschus 2g, Herba Aristolochiae 30g, Mentholum 30g, Radix Ilicis Pubescentis, each 15g system condensed cream of Sanguis Draxonis add in the rubber cream, then through being coated with cream, cutting, the lid lining, pack is made.
8, hydroxyl, demethyl speckle insect destructive of the roots of seedlings amine sheet is a kind of chemicotherapy drug combination, it can not only kill and wound cancerous cell, and immunosuppressant not, is the better anticancer agent of sending an expedition against.
It is characterized in that by prescription: hydroxyl, demethyl speckle insect destructive of the roots of seedlings amine 25g-30g, starch 2kg, Pseudobulbus Bletillae (Rhizoma Bletillae) powder 5kg, magnesium trisilicate 1kg, aluminium hydroxide 2kg, 35% ethanol 9-10kg, magnesium stearate 0.1kg, batch mixing, tabletting, and get.
9, the helexin sheet is a kind of chemicotherapy drug combination, and it also has mutation-resisting functional when having obvious cytotoxicity, be the comparatively ideal anticancer agent of sending an expedition against.
It is characterized in that by prescription: helexin 25g, oleanolic acid 500g, anethole 3000g, ginsenoside 1000g, starch 0.5kg, tapioca starch 2kg, stearic acid sodium sulfonate 0.35kg, magnesium carbonate 0.6kg, magnesium stearate 0.1kg, batch mixing, tabletting, and get.
10, blood quinoline methyl ether (HMME) lysate is a kind of not as the photosensitizer of the usefulness of quiet notes.
The blood quinoline methyl ether (HMME) that it is characterized in that preparing is made crude drug through chemolysis.
11, according to claim 10, monoclonal antibody blood quinoline methyl ether (HMME) Intravenous injection solution is the targeted drug of deriving of blood quinoline methyl ether (HMME) lysate.
It is characterized in that blood quinoline methyl ether (HMME) merges with human serum albumin (HSA) earlier, synthetic with the monoclonal antibody conjugation again, prepare Intravenous injection solution then.
12, according to claim 10, ferritin blood quinoline methyl ether (HMME) Intravenous injection solution be the magnetic control guide-localization medicine of deriving of blood quinoline methyl ether (HMME) lysate.
It is characterized in that ferritin and blood quinoline methyl ether (HMME) lysate elder generation natural fusion, prepare Intravenous injection solution then.
13, according to claim 10.Magnetic blood quinoline methyl ether (HMME) Intravenous injection solution is the magnetic control guide-localization medicine of deriving of blood quinoline methyl ether (HMME) lysate.
It is characterized in that preparation magnetic HMME microcapsule (particle diameter is below 0.8um) earlier, and then prepare Intravenous injection solution with blood quinoline methyl ether (HMME) lysate.
14, to alleviate quiet dropping liquid be a kind of adjustment cancer blood samples of patients pH value to cancer cachexia, dissolving digestion tumor cancer slough, when eliminating accompanying infection, the pathogenic bacteria of generation and virus, dissolve the blood clot that hemorrhage back produces, eliminate edema, abscess is got rid of hydrops, reduce blood agglutinated degree, be beneficial to these carcinous rubbish, toxin such as cancer slough, the internal milieu improving agent that excretes as early as possible, and cancer cachexia to alleviate quiet dropping liquid still be a kind of chemicotherapy improving agent.
It is characterized in that according to cancer blood samples of patients pH value preparation lysozyme papain trypsin complex NaHCO 3Quiet dropping liquid.
15, the quiet dropping liquid of polyinosini-Thymosin-Radix Isatidis is not only the auxilliary mutually immunomodulator of a kind of attack and defense, but also is that a kind of chemicotherapy is supported synergist.
It is characterized in that the preparation polyinosinic acid-plain F5-Radix Isatidis of breast pancreas mixture earlier, and then the quiet dropping liquid of preparation Nacl.
CN 00117845 2000-05-08 2000-05-08 X-ray magnetic therapy machine for PDT therapy of cancer by combining radiatherapy with chemicotherapy and its medicine Pending CN1316279A (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101927065A (en) * 2009-01-16 2010-12-29 北卡罗来纳大学查珀尔希尔分校 The compact microbeam radiation system and method that is used for treatment of cancer and research
US10835199B2 (en) 2016-02-01 2020-11-17 The University Of North Carolina At Chapel Hill Optical geometry calibration devices, systems, and related methods for three dimensional x-ray imaging
US10980494B2 (en) 2014-10-20 2021-04-20 The University Of North Carolina At Chapel Hill Systems and related methods for stationary digital chest tomosynthesis (s-DCT) imaging

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101927065A (en) * 2009-01-16 2010-12-29 北卡罗来纳大学查珀尔希尔分校 The compact microbeam radiation system and method that is used for treatment of cancer and research
CN101927065B (en) * 2009-01-16 2014-12-17 北卡罗来纳大学查珀尔希尔分校 Compact microbeam radiation therapy systems and methods for cancer treatment and research
US10980494B2 (en) 2014-10-20 2021-04-20 The University Of North Carolina At Chapel Hill Systems and related methods for stationary digital chest tomosynthesis (s-DCT) imaging
US10835199B2 (en) 2016-02-01 2020-11-17 The University Of North Carolina At Chapel Hill Optical geometry calibration devices, systems, and related methods for three dimensional x-ray imaging

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