CN1144089A - Water-soluble gossypol preparation and its preparing method - Google Patents
Water-soluble gossypol preparation and its preparing method Download PDFInfo
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Abstract
The present invention relates to a water-soluble gossypol preparation and its preparation method. Said preparation is composed of (wt%) 0.01-99.99% of gossypol as active component and 99.99-0.01% of medicinal carrier. The invented gossypol preparation has good water solubility, is easy to be absorbed by human body, and can reduce side effect of stomach and intestinal tract, raise medicine effect and reduce dosage, and can be made into oral liquor, injection, powder, tablet and capsule, etc..
Description
The invention belongs to gossypol preparation and preparation method thereof technical field.
Gossypol (Gossypol) is present in the Malvaceae plant cotton (GossypiumHerbaceum L.)." Chinese medicine voluminous dictionary " pointed out once that gossypol has antitussive action and antibiotic and antivirus action, also had antitumaous effect; In addition, gossypol was also once tested is used as men's spermicide antifertility drug.In the last few years, antitumaous effect for gossypol has had further research, clinical when being used for the treatment of cancer, gossypol not only can be killed cancerous cell specificity, under the doses condition: can also regulate immune status, the leukocyte increasing number improves Normocellular metabolism, has strengthening vital QI to eliminate pathogenic factors, constitutional effect.Thereby, being suitable for especially because of various reasons can not be by the cancer drug that presses down of the alternative chemotherapy of chemotherapy or operation back, for example be used for diseases such as pulmonary carcinoma, esophageal carcinoma, gastric cancer, intestinal cancer, hepatocarcinoma, leukemia, simultaneously, because medicine can be broken through multiple blood medicine barrier in the body, therefore also be applicable to diseases such as the brain cancer, carcinoma of prostate, choriocarcinoma, also applicable hysteromyoma, head benign tumor etc.
But, because gossypol is fat-soluble, being subjected to the restriction of dosage form in the preparation, is to make oral capsule at first, makes gastric soluble tablet or enteric coatel tablets after improve. and also there are some shortcomings in this class dosage form, influenced the performance of drug effect, for example: 1. the time of staying is long in gastrointestinal tract, is not easy dissolving, is difficult for being absorbed by body, be difficult for the performance drug effect, cause dosage to increase; 2. because local excessive concentration during medicine dissolution, easily the stimulating gastrointestinal road and produce side reaction such as xerostomia, slow slow-witted, feel sick, vomiting, abdominal distention and diarrhoea etc.
Purpose of the present invention is the shortcoming that overcomes existing gossypol preparation, develops a kind of water-soluble gossypol preparation of high-efficiency low-toxicity.
The invention provides a kind of water-soluble gossypol preparation (trade name " Gu Kang "), said preparation is that active ingredient and pharmaceutical carrier are formed with the gossypol.
In the water-soluble gossypol preparation of the present invention, the content proportioning of gossypol and pharmaceutical carrier is that the gossypol that contains 0.01-99.99% is made 100% composition with the pharmaceutical carrier that contains 99.99-0.01% with arbitrary proportion.
Water-soluble gossypol preparation of the present invention, active ingredient gossypol wherein (medicinal specification) can commercially availablely obtain, and pharmaceutical carrier has balanced electrolyte solution, buffer agent, PH regulator, binding agent, lubricant, disintegrating agent, cosolvent, correctives etc.Wherein said pharmaceutical carrier balanced electrolyte solution can be a sodium chloride, compound NaCl (is sodium chloride-containing 0.82～0.90 gram among every 100ml, potassium chloride 0.025～0.035 gram, crystallization of calcium chloride 0.03～0.36 gram), sodium bicarbonate--normal saline (being that every 100ml solution contains 1.3 gram sodium bicarbonate), sodium lactate--normal saline (being to contain 1.87 gram sodium lactates in every 100ml solution), the rectal dialysis solution (is sodium chloride-containing 0.6 gram in every 100ml solution, sodium bicarbonate 0.2 gram, potassium chloride 0.048 gram, magnesium sulfate 0.031 gram, calcium lactate 0.077 gram, glucose 1.5 grams or Krebs-Henseleit solution (are sodium chloride-containing 0.692 gram in per 1 00 ml solns, potassium chloride 0.035 gram, calcium chloride 0.028 gram, potassium dihydrogen phosphate 0.016 gram, magnesium sulfate 7H
2O 0.029 gram, sodium bicarbonate 0.21 gram, glucose 0.21 gram) etc.; Buffer agent is glycine or other each seed amino acid except that basic amino acid; The PH regulator is a hydrochloric acid; Binding agent is edible cellulose or starch etc.; Lubricant is magnesium stearate or Pulvis Talci etc.; Disintegrating agent is dried starch and modified form starch, alginic acid and glue, kaolin etc.; Cosolvent is Polyethylene Glycol, Tween 80, propylene glycol or glycerol etc.; Correctives is a sucrose etc.
Water-soluble gossypol preparation of the present invention can be oral liquid, powder, hard capsule, soft capsule, tablet or injection.
Water-soluble gossypol preparation warp of the present invention and the comparative efficacy test and the toxicological test that have fat-soluble gossypol tablet work now, show its superiority, as follows the row result of the test: one, the comparative efficacy test of water-soluble gossypol preparation (Gu Kang) and fat-soluble gossypol preparation (gossypol sheet): the 1. anticarcinogenic effect of more ancient health and gossypol suspension (representing the gossypol sheet).
| Cancerous cell half lethal dose LD 50 | ||||
| In vitro tests | The intraperitoneal injection in vivo test | |||
| Medicine | Human leukemia K562 cell strain | Mouse cervical cancer PU5 cell strain | Mice Ehrlich ehrlich ascites carcinoma | Mice Ehrlich ehrlich ascites carcinoma |
| Gu Kang | 13μg/ml | ?10.5μg/ml | ?19μg/ml | ?6.4mg/Kg |
| The gossypol sheet | 331μg/ml | ?105μg/ml | ?142μg/ml | ?16.3mg/Kg |
2. more ancient health and gossypol suspension (representing the gossypol sheet) are to the biological effect of rat.
To gossypol biological effect or clinical studies, all paid attention to its spermicide antifertility action, representative animal model is a rat in the past.In order to estimate the biological effect of the ancient health of new dosage form,, can do one with the gossypol sheet and intuitively compare so still select spermicide effect to rat.See the following form.
Gu Kang and gossypol suspension are to the comparison of the influence of rat sperm biological effect
| Medicament categories | The gossypol sheet | Gu Kang | Contrast | ||||||
| Drug level (mg/Kg body weight) | ?6 | ?12 | ?18 | ?30 | ?6 | ?12 | ?18 | ?30 | |
| Sperm mortality rate % | ?0 | ?0 | ?50 | ?100 | ?37 | ?53 | ?58 | ?100 | ?0 |
Find out from experimental result, (represent the gossypol sheet to gavage) in the gossypol sheet group with the gossypol suspension, under the situation of low dosage, be that every Mus is irritated stomach 6mg/Kg and 12mg/Kg once a day, around the continuous irrigation, under this dosage condition, the sperm in the rat deferent duct is all survived, and does not reach the onset dosage that gossypol is killed sperm as yet; But ancient health just can be killed the approximately sperm (37%, 53%) of half under this kind dosage condition, is about as much as the effect of killing sperm (50%) of gossypol group when once irritating stomach 18mg/Kg.When once irritating the stomach amount when reaching 30mg/Kg, no matter be that Gu Kang or gossypol sheet all can 100% be killed sperm, this is two kinds of common antifertility dosage of dosage form.Illustrate that ancient health has lower biological effect onset concentration than the gossypol sheet, but antifertility concentration the two is identical.Illustrate that ancient health absorbs better in vivo.
3. the research of ancient health and gossypol sheet combination rate in the white mice liver.
Purpose be comparison under oral route, the speed that Gu Kang and gossypol sheet absorb in the white mice the intestines and stomach, and after medicine enters liver, the relatively difference of free state and combined state quantity.
1. the comparison on gossypol content and absorption peak in the liver.
Take medicine (being divided into mensuration 7 times) in back 16 hours, Gu Kang enters the amount (measuring summation for 7 groups) of liver and compares comparatively with the gossypol suspending agent: 88.16 ± 2.69 (Gu Kang)＞67.2 ± 1.00 (gossypol sheet), (P=0.0018＜0.01), it is extremely remarkable that numerical value differs.Therefore it is not good enough to infer that the gossypol sheet may dissolve in intestinal, understands some amount and is drained in stool and waste.Peak in after gavaging 12 hours of content peak value 8 hours after gavaging in the liver of Gu Kang, gossypol sheet, the peak value of gossypol sheet was postponed 4 hours, showed dissolving when Gu Kang need not flower in the intestines and stomach, thereby to absorb than gossypol be fast.
2. the comparison of combination rate in the liver.
The ratio (combined state/free state) of the combined state of gossypol and free state content in liver, when gavaging with the gossypol sheet, the meansigma methods of 7 mensuration is 1.78 ± 0.09; Gavage with Gu Kangshi, meansigma methods is 1.24 ± 0.04, and both are all greater than 1, and promptly gossypol mainly exists with the form of combined state in animal body.± 0.04 (Gu Kang)＜1.78 ± 0.09 1.24 (gossypol sheet), (P=0.0051＜0.01) represents the two because the dosage form difference, enter liver after, the combined state of Gu Kang is less than gossypol sheet group, i.e. the Cf height of ancient health.In the Gu Kang group, when absorbing peak value (gavaging back 8 hours), test bit shows free value greater than associated value simultaneously, combined state/free state=0.79 ± 0.02, and gossypol sheet group does not then have this kind phenomenon.Promptly because the quick good absorption of a large amount of gossypols of ancient health group, gossypol in liver with the restriction that is subjected to space-time that combines of tissue, thereby emerge more free gossypol, behind blood circulation, the concentration that reaches target cell is also high, is beneficial to the performance of biological effect.3. conclusion:
White mice is after gavaging gossypol, and in preceding 16 hours, gossypol absorbs the amount that enters liver, and Gu Kang is greater than the gossypol sheet, and promptly ancient Kang Rongyi is absorbed less wastage; After entering liver, the combination rate of gossypol sheet is greater than ancient health.Therefore, in a single day Gu Kang is absorbed, and has more free gossypol and flows to blood, enters target.This shows that Gu Kang is better than the gossypol tablet at the intravital biological effect of machine.Two, the toxicological test of water-soluble gossypol preparation (Gu Kang): 1, animal acute toxicity test
The gossypol sheet is to the existing clear and definite conclusion of the half lethal dose of white mice: Shanghai Institute of Pharmaceutical Industry in 1973 and gradually river people health test institute to mice by intraperitoneal injection gossypol, LD
50Value is 26mg/Kg.Therefore in order to understand the acute toxicity size of ancient health, be laboratory animal with the white mice still, do the comparison of lumbar injection.The result shows the white mice half lethal dose LD of ancient health
50=118.5mg/Kg is about 5 times of gossypol sheet, and promptly toxicity is significantly less than the gossypol sheet.2, long-term toxicity test for animals
With the rat is animal model, studies the long term toxicity of oral ancient health.The result is presented under 2 times of ancient health spermicide onset dosage (6mg/Kg) conditions with 5 multiple doses, and during gavaging in six months and withdraw a back middle of the month, the growth of rat all is better than the blank group, is quick on the draw, and body constitution is strong.Under the dosage condition of 10 times of onset dosage, rat first trimester body weight gain is higher than matched group, and the trimestral growth in back obviously descends, and body weight is not as matched group.Do the inspection of sperm survival rate after the drug withdrawal, 100% survival of matched group sperm, 0% survival of medicine group.Show long-term oral ancient health, stimulating growth is arranged than low dosage, constitutional effect, and can not influence the biological effect of medicine.Higher dosage is unfavorable for the growth of body.The ancient health of suggestion clinical practice is to be advisable than low dosage.Above-mentioned result of the test shows that water-soluble gossypol preparation of the present invention (Gu Kang) has following advantage:
1, water-soluble gossypol preparation of the present invention (Gu Kang) enters intestines and stomach and can not produce the intestines and stomach irritant reaction, this is because it is to exist with the aqueous solution form, and concentration is very low, can further be diluted with water to weak solution when taking, body is rapid and abundant to the absorption of medicine, so drug diffusion is even.Aqueous solution also has the advantage of relative tablet uniqueness simultaneously, and this is to control the dosage of oral drugs as required arbitrarily, thereby avoids under medication or excessive by unnecessary dose and the infringement to body that cause.
2, water-soluble gossypol preparation of the present invention (Gu Kang) is that than the gossypol sheet is easier body absorbs.Show that from the result of the test of " to the comparison of the influence of rat biological effect " it has lower onset biology dosage than the gossypol sheet, thereby oral dose also can reduce, side reaction also reduces thereupon.From the just soluble above-mentioned phenomenon of the result of the test of " research of the combination rate the white mice liver ": gossypol sheet relatively, the gossypol of Gu Kangzhong can be absorbed fast well by body, and enter behind the liver combination rate with tissue less than the gossypol sheet, thereby Cf is higher.This be because the gossypol in a large amount of ancient health by fast Absorption, gossypol in liver with tissue combine the restriction that is subjected to space-time, enter blood circulation thereby emerge more free gossypol, the concentration that reaches target cell is also high, is beneficial to giving full play to of biological effect.Graft Versus Tumor with gossypol is an example, and clinical dosage in the past is 30～60mg/ day, and is existing with ancient health antitumor, and clinical amount oral on probation to child is 6mg/ day, two kinds of 12mg/ days and to adult's 12mg/ day, 24mg/ day, 36mg/ day three kinds of dosage.Because the tonic effect of low dosage, the effect of enhance immunity function causes and can doublely control various pathological symptoms: as pain relieving, the ascites pleural fluid that stops blooding, disappears, strengthen sleep and appetite, increase normal blood cell and hematoblastic amount, the body temperature of reduction fever patient etc.
3, the result of the test of inside and outside shows that water-soluble gossypol preparation of the present invention kills the ability of cancerous cell raising is arranged.The cell in vitro culture experiment, because its dissolving in water improves greatly, drug effect increases by 10 to 20 times; Test for the intravital cancer that presses down of animal, show that also medicine makes the half lethal dose LD of half cancer cell death
50, Gu Kang is about 1/3 of gossypol sheet, and promptly drug effect improves three times.Help reaching the purpose of treatment with less medicine.Simultaneously, because the toxic and side effects of the old relatively dosage form of novel form is littler, drug effect is higher, therefore to improving original all therapeutic efficiencies of gossypol, and as antibiotic, cough-relieving, treatment metrorrhagia, scald, and men's spermicide antifertility etc., all can play a role.
Another object of the present invention provides the preparation method of water-soluble gossypol preparation.The preparation method of water-soluble gossypol preparation of the present invention is to get the water of total amount 9/10 volume, boil the balanced electrolyte solution of back adding 135～150mM amount and 10% cosolvent, stirring is cooled to 60 ℃～80 ℃, the gossypol and the 24mM amount glycine that add 0.4～0.8mM amount then, stirred 1～2 hour, and be cooled to 40 ℃, regulate PH to 6.0～7.0 with hydrochloric acid, be diluted to total amount with water at last, behind cooling, filtration and sterilising filtration, make dosage form.
In the preparation of water-soluble gossypol preparation of the present invention, gossypol can commercially availablely obtain, and described water can be deionized water, triply distilled water or water for injection; Described cosolvent is Polyethylene Glycol, Tween 80, propylene glycol or glycerol etc.; Described balanced electrolyte solution can be the ion concentration balanced electrolyte solution such as the Krebs-Henseleit solution of sodium chloride solution, ringer's solution (sodium chloride-containing, potassium chloride, calcium chloride), sodium bicarbonate--normal saline, sodium lactate--normal saline, the rectal dialysis solution (sodium chloride-containing, sodium bicarbonate, potassium chloride, magnesium sulfate, calcium lactate, glucose) or imitative serum; Described buffer agent is glycine or other each seed amino acid except that basic amino acid.
Can prepare aqueous solution gossypol day clothes liquid, injection, powder, hard capsule, soft capsule, tablet etc. with method of the present invention.
Aqueous solution gossypol preparation preparation method of the present invention is easy, is suitable for the scale suitability for industrialized production.
Example 1, preparation water-soluble gossypol oral liquid
In two neck flasks, add 900 milliliters of deionized waters (or triply distilled water), boil.Dissolve in 9 gram sodium chloride (or other balanced electrolyte solution of a great deal of), add 100 gram Polyethylene Glycol again
2000, constantly agitating solution is slightly waited and is chilled to 80 ℃, adds 0.62 gram gossypol and 1.8 gram glycine, and 80 ℃ of holding temperatures are two hours in constantly stirring, and all dissolve to gossypol.Wait to be chilled to 40 ℃, transfer pH to 6.0～6.5, add deionized water slowly to 1000 milliliters of cumulative volumes with 1N hydrochloric acid.Cooling, buchner funnel filters, and filtrate reuse antibacterial funnel filters.The filtrate bottling, 100 ℃ of water-baths sterilization in 20 minutes.After quality testing.Example 2, preparation water-soluble gossypol oral liquid
Press the preparation of example one same procedure.Difference is to be that sodium chloride-containing 0.6 gram in per 100 milliliters, sodium bicarbonate 0.2 gram, potassium chloride 0.048 gram, magnesium sulfate 0.031 gram, calcium lactate 0.077 gram, glucose 1.5 grams substitute sodium chloride solution with the rectal dialysis solution.Example 3, preparation water-soluble gossypol oral liquid
Press the preparation of example one same procedure.Difference is to be sodium chloride-containing 0.692 gram in per 100 ml solns, potassium chloride 0.035 gram, calcium chloride 0.028 gram, potassium dihydrogen phosphate 0.016 gram, magnesium sulfate 7H with Krebs-Henseleit solution
2O0.029 gram, sodium bicarbonate 0.21 gram, glucose 0.21 gram substitute sodium chloride solution.Example 4, preparation water-soluble gossypol injection
Except that following 3, prepare by example one same procedure: (1) water is previously prepared water for injection.(2) in the above-mentioned oral liquid gossypol feed intake be 0.62 the gram, injection change into 0.12 the gram.The concentration that makes gossypol is 0.1mg/ml.(3) filtrate bottling ampere bottle.Example 5, preparation water-soluble gossypol injection
Press the preparation of example four same procedure.Difference is with compound sodium chloride injection, and sodium chloride-containing 0.82～0.9 gram, potassium chloride 0.025～0.035 gram, crystallization of calcium chloride 0.03～0.36 gram substitute sodium chloride solution among promptly every 100ml.Example 6, preparation water-soluble gossypol injection
Press example four same procedure preparations, difference is to be to contain 1.3 gram sodium bicarbonate in per 100 ml solns to substitute sodium chloride solution with sodium bicarbonate-normal saline.Example 7, preparation water-soluble gossypol injection
Press example four same procedure preparations, difference is to be to contain 1.87 gram sodium lactates in per 100 ml solns to substitute sodium chloride solution with sodium lactate-normal saline.Example 8, preparation water-soluble gossypol powder
In two neck flasks, add 900 milliliters of deionized waters (or triply distilled water), boil.Dissolve in 9 gram sodium chloride (or other balanced electrolyte solution of a great deal of), add 100 gram Polyethylene Glycol again
2000, constantly agitating solution slightly waits to be chilled to 80 ℃, adds 1.23 gram gossypols and 1.8 gram glycine, and 80 ℃ of holding temperatures are two hours in constantly stirring, and all dissolve to gossypol.Wait to be chilled to 40 ℃, transfer pH to 6.0～6.5, add deionized water slowly to 1000 milliliters of cumulative volumes with 1N hydrochloric acid.Cooling, buchner funnel filters, and filtrate reuse antibacterial funnel filters.The filtrate bottling.With following prescription (sodium chloride 0.30 gram, potassium citrate 0.69 gram (or potassium chloride 0.15 gram), sodium bicarbonate 0.25 gram, anhydrous glucose 20 grams) mixing, pulverize and cross 80 mesh sieves.In the mixing powder, add 10 milliliters of above-mentioned filtrates, mixing.Dry in freezer dryer, in pack into aluminium foil plastic bag or the bottle, the sealing bottleneck.Example 9, preparation water-soluble gossypol hard capsule
In two neck flasks, add 900 milliliters of deionized waters (or triply distilled water), boil.Dissolve in 9 gram sodium chloride (or other balanced electrolyte solution of a great deal of), add 100 gram Macrogol 2000, constantly agitating solutions again, slightly wait to be chilled to 80 ℃, add 2.45 gram gossypols and 1.8 gram glycine, 80 ℃ of holding temperatures are two hours in constantly stirring, and all dissolve to gossypol.Wait to be chilled to 40 ℃, transfer pH to 6.0～6.5, add deionized water slowly to 1000 milliliters of cumulative volumes with 1N hydrochloric acid.Cooling, buchner funnel filters, and filtrate reuse antibacterial funnel filters.The filtrate bottling.In 1000 milliliters of filtrates, dissolve in glycine 20～100 grams slowly, add edible cellulose 50～200 grams again, make into the thixotropic fluid medicine, be fed in the gelatin capsule for medicine of having prepared, become the lyophilization capsule with the freezer dryer lyophilization then.Example 10, preparation water-soluble gossypol soft capsule
Make commensurability thixotropic fluid medicine to wherein adding 10～100 gram glycerol or propylene glycol by example nine same procedure, mixing can prevent the induration of soft capsule.In full-automatic or automanual molding press, the mixing medicinal liquid is placed the soft gelatin film of having prepared, in steel mould, carry out pelleting, after surface clean, drying and check, can be packaged as finished product.Example 11, preparation water-soluble gossypol tablet
In two neck flasks, add 900 milliliters of deionized waters (or triply distilled water), boil.Dissolve in 9 gram sodium chloride (or other balanced electrolyte solution of a great deal of), add 100 gram Polyethylene Glycol again
2000, constantly agitating solution is slightly waited and is chilled to 80 ℃, adds 2.45 gram gossypols and 1.8 gram glycine, and 80 ℃ of holding temperatures are two hours in constantly stirring, and all dissolve to gossypol.Wait to be chilled to 40 ℃, transfer pH to 6.0～6.5, add deionized water slowly to 1 000 milliliters of cumulative volumes with 1N hydrochloric acid. cooling, buchner funnel filters, and filtrate reuse antibacterial funnel filters.The filtrate bottling.Prepare burden by following prescription:
| Supplementary material | Every consumption | Per 100,000 consumptions |
| Water-soluble gossypol | 12mg (filtrate 1.25ml) | (1.2Kg filtrate 125L) |
| Starch | 50mg | 5.0Kg |
| Starch slurry (10%) | About 38-48mg | About 3.8-4.8Kg |
| Magnesium stearate | 0.83mg | 0.08?3Kg |
| Pulvis Talci | 35mg | 3.5Kg |
| Sucrose | 35mg | 3.5Kg |
| Cellulose Acetate Phthalate | 3mg | 0.3Kg |
Above material is stirred, make soft material, granulate and granulate by 14 mesh sieves, wet granular should be evenly solid, goes into the freezer dryer drying, with the dark radian punch die of φ 6m/m tabletting.Wrap up with outer coatings through screening qualified tablet.Coating material is more suitable with the mode of semi-film coating.Promptly press earlier the sugarcoating layer mode, wrap sealing coat, sub-coat, reduce the level of sugar coating then, 2～3 layers get final product, and wrap 2～3 layers in thin film dress material again, and the clothing layer is firm like this, and protective value is good.The various methyl of the optional usefulness of thin film dress material, ethyl, propyl cellulose all can., after quality examination is qualified, carries out mmic package with aluminum-plastic composite membrane or metal foil film and be advisable through the tablet of outer coatings parcel, can be hedged off from the outer world once more.Every contains water solublity gossypol 12mg.
Claims (4)
1. water-soluble gossypol preparation, it is characterized in that this water-soluble gossypol preparation is made up of as active component and pharmaceutical carrier gossypol, wherein the content proportioning of gossypol and pharmaceutical carrier is to contain 0.01～99.99% gossypol and 99.99～0.01% pharmaceutical carrier is made 100% composition with arbitrary proportion.
2. the preparation method of a water-soluble gossypol preparation as claimed in claim 1, it is characterized in that this preparation method is to get the water of total amount 9/10 volume, boil the balanced electrolyte solution of back adding 135～150mM amount and 10% cosolvent, stirring is cooled to 60 ℃～80 ℃, add the gossypol of 0.4～0.8mM amount and the amount glycine of 24mM then, stirred 1～2 hour, be cooled to 40 ℃, regulate pH to 6.0～7.0 with hydrochloric acid, be diluted to total amount with water at last, behind cooling, filtration and sterilising filtration, make dosage form.
3. according to claim 1 and 2 described water-soluble gossypol preparations, it is characterized in that wherein said pharmaceutical carrier is balanced electrolyte solution, buffer agent, PH regulator, binding agent, lubricant, disintegrating agent, cosolvent, correctives.
4. according to claim 1,2 and 3 described water-soluble gossypol preparations is characterized in that wherein said pharmaceutical carrier balanced electrolyte solution can be a sodium chloride, compound NaCl (is sodium chloride-containing 0.82～0.90 gram among every 100ml, potassium chloride 0.025～0.035 gram, crystallization of calcium chloride 0.03～0.36 gram), sodium bicarbonate-normal saline (being that every 100ml solution contains 1.3 gram sodium bicarbonate), sodium lactate-normal saline (being to contain 1.87 gram sodium lactates in every 100ml solution), the rectal dialysis solution (is sodium chloride-containing 0.6 gram in every 100ml solution, sodium bicarbonate 0.2 gram, potassium chloride 0.048 gram, magnesium sulfate 0.031 gram, calcium lactate 0.077 gram, glucose 1.5 grams or KREBS-HENSELEIT solution (are sodium chloride-containing 0.692 gram in per 100 ml solns, potassium chloride 0.035 gram, calcium chloride 0.028 gram, potassium dihydrogen phosphate 0.016 gram, magnesium sulfate 7H
2O 0.029 gram, sodium bicarbonate 0.21 gram, glucose 0.21 gram); Buffer agent is glycine or other each seed amino acid except that basic amino acid; The PH regulator is a hydrochloric acid; Binding agent is edible cellulose or starch; Lubricant is magnesium stearate or Pulvis Talci; Disintegrating agent is dried starch and modified form starch, alginic acid and glue, kaolin; Cosolvent is Polyethylene Glycol, Tween 80, propylene glycol or glycerol; Correctives is a sucrose.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN95111745A CN1067549C (en) | 1995-09-01 | 1995-09-01 | Water-soluble gossypol preparation and its preparing method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN95111745A CN1067549C (en) | 1995-09-01 | 1995-09-01 | Water-soluble gossypol preparation and its preparing method |
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| CN1144089A true CN1144089A (en) | 1997-03-05 |
| CN1067549C CN1067549C (en) | 2001-06-27 |
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| CN95111745A Expired - Fee Related CN1067549C (en) | 1995-09-01 | 1995-09-01 | Water-soluble gossypol preparation and its preparing method |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100413493C (en) * | 2003-06-11 | 2008-08-27 | 中国科学院动物研究所 | Use of gossypol and its derivative in preparation of drug for leukemia / bone marrow cancer |
| CN113143853A (en) * | 2021-03-30 | 2021-07-23 | 赜誉(上海)生物科技有限公司 | Preparation method of efficient cotton polyphenol traditional Chinese medicine extract aqueous solution preparation |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4297341A (en) * | 1980-05-09 | 1981-10-27 | University Of Illinois Foundation | Spermicidal composition |
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1995
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100413493C (en) * | 2003-06-11 | 2008-08-27 | 中国科学院动物研究所 | Use of gossypol and its derivative in preparation of drug for leukemia / bone marrow cancer |
| CN113143853A (en) * | 2021-03-30 | 2021-07-23 | 赜誉(上海)生物科技有限公司 | Preparation method of efficient cotton polyphenol traditional Chinese medicine extract aqueous solution preparation |
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| Publication number | Publication date |
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| CN1067549C (en) | 2001-06-27 |
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