CN102784102A - Tetraodotoxin oral liquid state preparation and preparation method thereof - Google Patents
Tetraodotoxin oral liquid state preparation and preparation method thereof Download PDFInfo
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- CN102784102A CN102784102A CN2012103095343A CN201210309534A CN102784102A CN 102784102 A CN102784102 A CN 102784102A CN 2012103095343 A CN2012103095343 A CN 2012103095343A CN 201210309534 A CN201210309534 A CN 201210309534A CN 102784102 A CN102784102 A CN 102784102A
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- fugu ocellatus
- ocellatus toxin
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Abstract
The invention discloses a tetraodotoxin oral liquid state preparation and a preparation method of the tetraodotoxin oral liquid state preparation. The oral liquid state preparation contains tetraodotoxin, cosolvent, solubilizer, antioxidant, preservative, high permeable substance for opening BBB (blood brain barrier) and adjuvants. The preparation method is as follows: completely dissolving tetraodotoxin by the cosolvent and the solubilizer, adding the antioxidant, the preservative, and the high permeable substance for opening BBB, and then adding the djuvants into the mixed solution for dissolving to obtain the tetraodotoxin oral liquid state preparation. The tetraodotoxin oral liquid state preparation provided by the invention can be used to relieve pain and give out of drug dependence, and has the characteristics of taking effect quickly, and being durable in efficacy, and strong in safety etc., and the product quality control is operable.
Description
Technical field
The present invention relates to a kind of Fugu ocellatus toxin liquid-state preparation and preparation method thereof, belong to medical technical field.
Background technology
In recent years, very burning hot to the research and development of Fugu ocellatus toxin new drug both at home and abroad.But up to now, it is clinical that Shang Weijian has the Fugu ocellatus toxin new drug formally to be applied to.Trace it to its cause, maybe not have analgesic effect relevant with single Fugu ocellatus toxin.Have researcher to find abroad, single Fugu ocellatus toxin aqueous injection is used for analgesia and is difficult to take effect, and the phenomenon that the experimenter has toxic reaction or local pain in clinical trial, also often occurs.
In the prior art, relevant Fugu ocellatus toxin soft capsule prepn mainly is the patent of invention that Huang causes strong application, and name is called " method for preparing of tetrodotoxin oil phase formulation ", and the patent No. is " ZL 200410080557.7 ".
According to test, there is following weak point in prior art:
1) prior art is that Fugu ocellatus toxin is dissolved in vegeto-animal oils and fats, because Fugu ocellatus toxin is wrapped up by oils and fats, can't fully therefrom separate, thereby can't the using dosage of active substance be detected, and product quality is difficult to control.The present invention can directly carry out content detection through HPLC to active substance because Fugu ocellatus toxin is to dissolve in water miscible material, makes the quality control of product have operability.
2) prior art is to have utilized liposoluble substance to have the characteristic of quick penetration blood brain barrier (BBB), and Fugu ocellatus toxin is dissolved in oils and fats.The present invention utilizes high osmosis materials such as carbamide, glycerin, mannitol, ethanol, galactose, arabinose, fructose, glucose, lactamide can open the characteristic of blood brain barrier (BBB), can improve the penetrance of Fugu ocellatus toxin to blood brain barrier (BBB) equally.
3) though prior art has good drug effect, because Fugu ocellatus toxin receives the oils and fats parcel, in oil preparation, can only slowly discharge, cause the Fugu ocellatus toxin onset slower.There is not this problem in the present invention, so onset is very fast.
Summary of the invention
The objective of the invention is to overcome the weak point of prior art, a kind of Fugu ocellatus toxin liquid-state preparation and preparation method thereof is provided.
Fugu ocellatus toxin liquid-state preparation of the present invention, described liquid-state preparation comprise the highly osmotic substance and the adjuvant of Fugu ocellatus toxin, cosolvent, solubilizing agent, antioxidant, antiseptic, open blood brain barrier.
Described cosolvent is selected from acetic acid, phosphoric acid or citric acid and sodium salt thereof.
Described solubilizing agent is selected from one or more among polyvinylpyrrolidone (PVP), polyoxyethylene hydrogenated Oleum Ricini HEL-40, the polyoxyethylene hydrogenated Oleum Ricini HEL-20.
Described antioxidant is selected from reduced glutathion, disodiumedetate, phytic acid, ascorbic acid and sodium salt thereof or arabo-ascorbic acid and sodium salt thereof.
Described antiseptic is selected from benzoic acid and its esters, sorbic acid and its esters, dehydroactic acid and sodium salt thereof, sodium diacetate, calcium propionate, sodium lactate or biological food antiseptic.
The highly osmotic substance of described open blood brain barrier is selected from carbamide, glycerin, mannitol, ethanol, galactose, fructose, glucose, arabinose or lactamide.
Described adjuvant is the non-oil substances of edible.
The non-oil substances of described edible is selected from liquid macrogol, glycerin, glycerin gelatine, pectin, propolis, alginate jelly or agar.
Described liquid macrogol is selected from PEG-200, PEG-300, PEG-400, PEG-600.
The method for preparing of Fugu ocellatus toxin liquid-state preparation of the present invention; May further comprise the steps: Fugu ocellatus toxin is fully dissolved through cosolvent, solubilizing agent, add antioxidant, antiseptic, and the highly osmotic substance of open blood brain barrier; Dissolve in adjuvant then, process the Fugu ocellatus toxin liquid-state preparation.
Fugu ocellatus toxin liquid-state preparation of the present invention draws on the basis of following experiment:
1. Fugu ocellatus toxin do not have significant analgesic activity to mice in acidic aqueous solution.
Test 1. mice hot plates and add sufficient test: 4 groups of mices; Wherein 3 administration groups are used Fugu ocellatus toxin respectively, and content is 0.1 μ g/ml, 0.2 μ g/ml and 0.4 μ g/ml, and consumption 0.2ml/ is (ip) only; 1 matched group uses normal saline, and consumption 0.2ml/ is (ip) only.After the administration 1 hour, adopt the mice hot plate to add sufficient test method(s), observe and compare the pain threshold of mice.The result shows not have significant difference (P＞0.05) after the administration of administration group with before the administration, does not also have significant difference (P＞0.05) with matched group.
Test the test of 2. mice acetic acid twistings: 4 groups of mices; Wherein 3 administration groups are used Fugu ocellatus toxin respectively, and content is 0.1 μ g/ml, 0.2 μ g/ml and 0.4 μ g/ml, and consumption 0.2ml/ is (ip) only; 1 matched group uses normal saline, and consumption 0.2ml/ is (ip) only.After the administration 1 hour,, observe and turn round the body number of times in the mice 15 minutes with 0.6% acetum 0.2ml injection each mice (ip).The result shows that administration group and matched group do not have significant difference (P＞0.05).
Above-mentioned result of the test is consistent with people's such as Cai Zhiji result of the test.(Cai Zhiji, Huang Zhiqiang, Pan Xinfu " the pharmacological research summary of homemade Fugu ocellatus toxin " Hebei aquatic science and technology, 1983,1:1-3)
Can draw: single Fugu ocellatus toxin does not have significantly effect to the mice analgesia in acidic aqueous solution.
Above-mentioned situation shows that the Fugu ocellatus toxin aqueous solution can not the analgesic reason be that it can not penetrate blood brain barrier, has only to let it see through blood brain barrier entering brain and nervus centralis, could produce the effect of treatment nervous system disease.
Fugu ocellatus toxin analgesic effect in oil preparation is fine, but quality control is very difficult.
The patent of invention of Huang Zhiqiang, its name is called " method for preparing of tetrodotoxin oil phase formulation ", and the patent No. is " ZL 200410080557.7 ", is Fugu ocellatus toxin to be dissolved in animal and plant fat process oral tetrodotoxin formulation.Said preparation has the analgesic effect of highly significant.This patent has solved the difficult problem that Fugu ocellatus toxin penetrates blood brain barrier, for good start has been created in the extensive use of Fugu ocellatus toxin.But; According to the unusual difficulty of the Fugu ocellatus toxin oil phase formulation quality control of the method for this patent preparation; The Fugu ocellatus toxin that reason is to dissolve in the oils and fats can not reclaim fully, and the time of shelving is long more, and the yield of recovery is low more; Although the drug effect of the patented product does not reduce, the content of active substance is difficult to obtain accurate quantitative analysis in the product.
Above-mentioned situation shows that the development of Fugu ocellatus toxin soft capsule should be paid attention to its effectiveness, pays attention to the operability of Fugu ocellatus toxin content detection in the product again.
the present invention combine the effectiveness and the quality controllability of Fugu ocellatus toxin.
Document shows that after Fugu ocellatus toxin got into the interior 30min of mice body through acidic aqueous solution, distribution situation was: blood 10.2%, lung 20.2%, small intestinal 9.0%, stomach 5.0%, liver 4.0%, large intestine 3.4%, kidney 5.0%, heart 0.5%, spleen 0.2%, brain 0.09%.This shows that the distribution of Fugu ocellatus toxin in brain only accounts for 0.09% of total amount, explain that single Fugu ocellatus toxin being difficult in water preparation sees through blood brain barrier (BBB)." Fugu ocellatus toxin distributes and dynamic metabolism in the mice body " Chinese Pharmacological such as (Liu Min, Zhao circulate a notice of 2006 Apr:22-4-507-8) innovating
Discovery of the present invention; Fugu ocellatus toxin not only can penetrate blood brain barrier (BBB) in oil phase formulation; It can penetrate blood brain barrier (BBB) equally after the material that has high infiltration characteristics with carbamide, glycerin, mannitol, ethanol, galactose, arabinose, fructose, glucose, lactamide etc. dissolves altogether, and in company with this type material permeance brain blood capillary; Get into the central nervous system, the performance drug effect.
Fugu ocellatus toxin carrier used in the present invention is water-soluble substances; Therefore; Can be with comparalive ease with Fugu ocellatus toxin from wherein separating, not only guarantee the river tetrodotoxin can see through blood brain barrier (BBB), and guaranteed the controllability and the detectability of Fugu ocellatus toxin content.
Fugu ocellatus toxin oral formulations of the present invention can be used for analgesia and gives up drug dependence, have onset rapidly, lasting medicine, characteristics such as high safety, control of product quality has operability, compared with prior art, the present invention has following technique effect:
1) prior art (being ZL 200410080557.7) is that Fugu ocellatus toxin is dissolved in vegeto-animal oils and fats, and the present invention is the material that Fugu ocellatus toxin is dissolved in non-oils.The former can't fully therefrom separate, thereby can't the using dosage of active substance be detected because Fugu ocellatus toxin is wrapped up by oils and fats, and product quality is difficult to control.The latter can directly carry out content detection through HPLC to active substance because Fugu ocellatus toxin is to dissolve in water-soluble substances, makes the quality control of product have operability.
2) prior art (being ZL 200410080557.7) is to have utilized liposoluble substance to have the characteristic of quick penetration blood brain barrier (BBB), and Fugu ocellatus toxin is dissolved in oils and fats.The present invention utilizes the formed breast grain of polyoxyethylene hydrogenated Oleum Ricini P-40 (or HEL-40) enclose medicine can penetrate the characteristics of blood brain barrier (BBB); Or utilize the high osmosis of materials such as carbamide, glycerin, mannitol, ethanol, galactose, arabinose, fructose, glucose, lactamide simultaneously; Thereby can increase the ratio that Fugu ocellatus toxin gets into nervus centralis, improve the bioavailability of Fugu ocellatus toxin.
3) product of prior art (being ZL 200410080557.7) development has good drug effect, and its drug effect of product of the present invention's development is identical with prior art products.But because the Fugu ocellatus toxin in the product of the present invention does not receive greasy parcel, therefore, the product of the release ratio prior art of drug effect comes soon.
The specific embodiment
Embodiment 1 preparation content is the Fugu ocellatus toxin soft capsule prepn of 2.5 microgram/grains
1. get pure article 50 mg of Fugu ocellatus toxin, citric acid 94.5 mg, sodium citrate 155.5 mg insert in the 100ml small beaker; Add pure water 100ml, dissolving to clarification, is got polyvinylpyrrolidone (PVP) 5 grams; Dissolve in the Fugu ocellatus toxin aqueous solution, stir, to clarification, subsequent use.
2. get pure water 100ml, put in the 500ml beaker, dissolve in glucose 100 g, dissolve in glutathion 100g; Dissolve in potassium sorbate 20g, room temperature stirs down, while stirring above-mentioned Fugu ocellatus toxin aqueous solution 100ml is injected fully; The dehydrated alcohol 200ml that reinjects continues to stir, and is subsequent use.
3. taking polyethylene glycol (400) 1500ml puts in the 2000ml beaker, heating, 60 ℃ of constant temperature; Stir,, stop heating, to room temperature to diluting shape; Limit stirring, limit will contain above-mentioned Fugu ocellatus toxin, glucose and the alcoholic acid solution of containing injects fully, and it is an amount of to add Polyethylene Glycol (400), regulates total amount to 2000ml; Continue to stir, get Fugu ocellatus toxin seed preparations 2000ml, subsequent use.
4. taking polyethylene glycol (400) 2000ml divides equally, puts 5000 ml beakers, heating; 60 ℃ of constant temperature are stirred to the dilution shape, stop heating, to room temperature; While stirring above-mentioned Fugu ocellatus toxin seed preparations is injected fully, continue to stir, until getting into the soft capsule production line.
5. above-mentioned tetrodotoxin formulation 4000ml is processed 20000 of soft capsules through capsule machine, the loading amount of every capsules is 0.2ml, and the content of Fugu ocellatus toxin is 2.5 microgram/grains.
Embodiment 2 preparation content be 2.0 micrograms/the Fugu ocellatus toxin syrup preparation
1. get pure article 5 mg of Fugu ocellatus toxin, citric acid 9.45 mg, sodium citrate 15.55 mg, polyvinylpyrrolidone (PVP) 5 mg put the 5ml cillin bottle, add medicinal water 3ml, and dissolving is to clarification, subsequent use.
2. get polyoxyethylene hydrogenated Oleum Ricini HEL-40 5-10 ml, put the 100ml beaker, stirring, heating, 60 ℃ of constant temperature, stir on the limit, and the limit splashes into Fugu ocellatus toxin solution 3ml fully, stirs, and to transparent, gets TTX/P40 solution.
3. get polyoxyethylene hydrogenated Oleum Ricini HEL-20 10-30 ml, splash into fully in the above-mentioned TTX/P40 solution, 60 ℃ of constant temperature stir, and to transparent, get TTX/P40+P7 solution.
4. get pure water 200 ml, insert in the 250ml beaker, stir under the room temperature, stir on the limit, and the limit is injected TTX/P40+P7 solution fully, continues to stir, and makes its emulsifying, gets the Fugu ocellatus toxin emulsion, subsequent use.
5. get 24 kilograms of pure water, insert 30 kilograms of agitators, stir, add 2 kilograms in mannitol simultaneously, 4 kilograms of glucoses, 2 kilograms of galactose, stir on the limit, and ascorbic acid and sodium salt 20 grams thereof are dissolved in the limit, dissolve in potassium sorbate 20g, process dextrose syrup, and are subsequent use.
6. the Fugu ocellatus toxin emulsion is injected the above-mentioned dextrose syrup that is stirring fully, continue to stir, it is fully mixed, simultaneously, add pure water, make its total amount reach 25 kilograms.
7. above-mentioned Fugu ocellatus toxin dextrose syrup is carried out packing for 25 kilograms, be filled into the special-purpose bottle of oral liquid, every bottled amount 10 ml make 2500 of Fugu ocellatus toxin oral syrups, the content of Fugu ocellatus toxin be 2.0 micrograms/.
Embodiment 3 preparation content are the Fugu ocellatus toxin soft capsule prepn of 2.0 microgram/grains
1. get pure article 40 mg of Fugu ocellatus toxin, citric acid 75.6 mg, sodium citrate 124.4 mg insert in the 10ml weighing botle, add pure water 5ml, and dissolving to clarification, gets the Fugu ocellatus toxin aqueous solution, and is subsequent use.
2. get vinylpyrrolidone (PVP) 15g, put in the 100ml beaker, add pure water 75ml, stirring at normal temperature; Dissolve to complete, stir on the limit, and the limit splashes into the Fugu ocellatus toxin aqueous solution in the above-mentioned weighing botle fully; Add ascorbic acid 10g again, potassium sorbate 10g, food coloring is an amount of; Continue to stir, dissolve to complete, subsequent use.
3. get glycerin 250ml, insert in the 500ml beaker, be heated to 55 ℃, constant temperature, stir on the limit, and the limit is injected above-mentioned TTX aqueous solution fully, continues to stir, and gets Fugu ocellatus toxin glycerin solution, and is subsequent use.
4. get glucose 2000 grams, put the 5000ml beaker, add pure water 1500ml, dissolve to complete; Stir, be heated to 55 ℃, constant temperature adds glycerin 2000ml; Stir, above-mentioned Fugu ocellatus toxin glycerin solution is injected fully, add glycerin while stirring; Make its total amount reach 4000ml, continue to stir, until getting into capsule machine.
5. above-mentioned tetrodotoxin formulation 4000ml is processed 20000 of soft capsules through capsule machine, the loading amount of every capsules is 0.2ml, and the content of Fugu ocellatus toxin is 2.0 microgram/grains.
Embodiment 4 preparation content are the Fugu ocellatus toxin soft capsule prepn of 1.0 microgram/grains
1. get pure article 20 mg of Fugu ocellatus toxin, citric acid 37.8mg, sodium citrate 62.2mg inserts in the 10ml weighing botle, adds pure water 5ml, and dissolving to clarification, gets the Fugu ocellatus toxin aqueous solution, and is subsequent use.
2. get vinylpyrrolidone (PVP) 15g, put in the 100ml beaker, add pure water 75ml, stirring at normal temperature; Dissolve to complete, stir on the limit, and the limit splashes into the Fugu ocellatus toxin aqueous solution in the above-mentioned weighing botle fully; Add ascorbic acid 10g again, potassium sorbate 10g, food coloring is an amount of; Continue to stir, dissolve to complete, subsequent use.
3. get dehydrated alcohol 150ml, put in the 1000ml beaker, stir under the room temperature, while stirring above-mentioned Fugu ocellatus toxin solution is injected fully, stir, stir on the limit, and the limit adds Polyethylene Glycol (400), makes its total amount reach 1000ml, gets the Fugu ocellatus toxin seed solution, subsequent use.
4. taking polyethylene glycol (400) 1000ml puts the 2000ml beaker, is heated to 55 ℃, and constant temperature stirs, and while stirring above-mentioned Fugu ocellatus toxin seed solution is injected fully, gets tetrodotoxin formulation 2000ml, and is subsequent use.
5. above-mentioned tetrodotoxin formulation 4000ml is processed 20000 of soft capsules through capsule machine, the loading amount of every capsules is 0.2ml, and the content of Fugu ocellatus toxin is 1.0 microgram/grains.
The medicinal effects of embodiment 5 Fugu ocellatus toxin liquid-state preparations detects
Will be edible to the volunteer with the tetrodotoxin formulation of embodiment 1-3 preparation, the result is following:
1) Xu certain, the man, 59 years old, pulmonary carcinoma late period, pain can't bear, and injects 3-5 dolantin every day and still can not ease pain fully.Take product of the present invention (content is the Fugu ocellatus toxin soft capsule of 2.0 microgram/grains), originally 3 days, every day 3 times; Each 3, reduced gradually afterwards, simultaneously; The access times of dolantin reduce thereupon, after 10 days, obey capsule every day and change into 2 times; Take 1 at every turn, inject dolantin every day and reduce to 2 times.After continuing to take medicine 30 days, dolantin is stopped using, and pain is controlled.
2) Wang, the woman, 61 years old, rheumatoid arthritis, the finger-joint enlargement, both hands respectively have 3 clinodactylys, and morning, pain was more serious, took prednisone throughout the year, and pain still can not be controlled.Take product of the present invention (content is the Fugu ocellatus toxin soft capsule of 1.0 microgram/grains), continue 30 days, sooner or later respectively obey 1 every day, and the consumption of prednisone is obeyed 3 from every day and is reduced to and obeys 1 every day, and pain has obtained control fully.
3) certain tumour hospital's in-patient department has patient with advanced cancer 17 people, wherein has volunteer 11 people to be ready to take product of the present invention.Lung cancer metastasis 4 people wherein, hepatoma Metastasis 2 people, esophageal carcinoma name stomach cancer metastasis 3 people, osteocarcinoma 1 people, lymphatic cancer 1 people.Among the volunteer, pain is not stopped person 5 people, and severe pain is not stopped person 6 people; Use morphine injection 4 people, use dolantin injection 5 people, take morphine 2 people.Take product of the present invention (Fugu ocellatus toxin content is the soft capsule of 2.5 microgram/grains) for 11 volunteers, also continue simultaneously to use original analgesia method, and replace original morphine and the dolantin that uses with product of the present invention gradually.After 30 days, have 2 people painless and whole, have 1 people to continue to use dolantin, reduce to 1 time for 6 times from every day, all the other 8 people continue to take product of the present invention, do not re-use morphine and dolantin injection.
4) temperature certain, the man, 43 years old, history of drug abuse 10 years was used one type of drugs of heroin more, was interrupted injection amphetamine drugs, it is invalid repeatedly to quit drug abuse.Afterwards; When using buprenorphine (shared) drug rehabilitation, take product of the present invention (content is the Fugu ocellatus toxin soft capsule of 2.5 microgram/grains) simultaneously, after the week with micro-Fugu ocellatus toxin; Stop to inject buprenorphine; Continue to take product of the present invention, drug addiction is not seen recurrence so far, intolerable withdrawal symptom do not occur yet.
5) leaf, the man, 35 years old, sucked heroin 5 years, use the buprenorphine drug rehabilitation repeatedly in narcotic house, form the buprenorphine dependency, produced and guarded against and inhale the consequence of having inhaled and having guarded against.Afterwards, when using the buprenorphine drug rehabilitation, take product of the present invention (Fugu ocellatus toxin content is the soft capsule of 1 microgram/grain), and took giving up continued, and through the one-year age observation, do not occur rebound phenomenon so far, heart addiction disappears equally.
6) Cao, the woman, 48 years old, rheumatic arthritis, ache all over the body, extremity are especially serious, take 3 of prednisones every day, and pain still can't be alleviated.Afterwards, give clothes product Fugu ocellatus toxin syrup of the present invention (content be 2.0 micrograms /), after 3 days, prednisone is reduced to 1 of every day, pain relief, and whole body is light, and after 30 days, pain is eliminated fully, still takes product of the present invention so far.
Claims (10)
1. a Fugu ocellatus toxin liquid-state preparation is characterized in that, described liquid-state preparation comprises the highly osmotic substance and the adjuvant of Fugu ocellatus toxin, cosolvent, solubilizing agent, antioxidant, antiseptic, open blood brain barrier.
2. Fugu ocellatus toxin liquid-state preparation according to claim 1 is characterized in that described cosolvent is selected from acetic acid, phosphoric acid or citric acid and sodium salt thereof.
3. Fugu ocellatus toxin liquid-state preparation according to claim 1 is characterized in that, described solubilizing agent is selected from one or more among polyvinylpyrrolidone, polyoxyethylene hydrogenated Oleum Ricini HEL-40, the polyoxyethylene hydrogenated Oleum Ricini HEL-20.
4. Fugu ocellatus toxin liquid-state preparation according to claim 1 is characterized in that, described antioxidant is selected from reduced glutathion, disodiumedetate, phytic acid, ascorbic acid and sodium salt thereof or arabo-ascorbic acid and sodium salt thereof.
5. Fugu ocellatus toxin liquid-state preparation according to claim 1; It is characterized in that described antiseptic is selected from benzoic acid and its esters, sorbic acid and its esters, dehydroactic acid and sodium salt thereof, sodium diacetate, calcium propionate, sodium lactate or biological food antiseptic.
6. Fugu ocellatus toxin liquid-state preparation according to claim 1 is characterized in that the highly osmotic substance of described open blood brain barrier is selected from carbamide, glycerin, mannitol, ethanol, galactose, fructose, glucose, arabinose or lactamide.
7. Fugu ocellatus toxin liquid-state preparation according to claim 1 is characterized in that, described adjuvant is the non-oil substances of edible.
8. Fugu ocellatus toxin liquid-state preparation according to claim 1 is characterized in that, the non-oil substances of described edible is selected from liquid macrogol, glycerin, glycerin gelatine, pectin, propolis, alginate jelly or agar.
9. Fugu ocellatus toxin liquid-state preparation according to claim 1 is characterized in that described liquid macrogol is selected from PEG-200, PEG-300, PEG-400 or PEG-600.
10. according to the method for preparing of any described Fugu ocellatus toxin liquid-state preparation among the claim 1-9; It is characterized in that; May further comprise the steps: Fugu ocellatus toxin is fully dissolved through cosolvent, solubilizing agent, add antioxidant, antiseptic, and the highly osmotic substance of open blood brain barrier; Dissolve in adjuvant then, process the Fugu ocellatus toxin liquid-state preparation.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103876243A (en) * | 2012-12-21 | 2014-06-25 | 贵州天刺力食品科技有限责任公司 | Compound antioxidant |
| CN104352499A (en) * | 2014-09-18 | 2015-02-18 | 赵继红 | Drug combination for analgesia, anesthesia or drug rehabilitation |
| CN107668723A (en) * | 2017-10-19 | 2018-02-09 | 重庆师范大学 | A kind of plastic bottle L arabinose oral liquids easy to break and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1178469A (en) * | 1995-01-20 | 1998-04-08 | 埃斯基尔·埃尔默 | Treatment of cerebral ischemia and cerebral damage with neuroprotective agent |
| CN102327274A (en) * | 2011-09-02 | 2012-01-25 | 江苏京甲药业有限公司 | Adrenal cortical hormone compound preparation |
-
2012
- 2012-08-28 CN CN2012103095343A patent/CN102784102A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1178469A (en) * | 1995-01-20 | 1998-04-08 | 埃斯基尔·埃尔默 | Treatment of cerebral ischemia and cerebral damage with neuroprotective agent |
| CN102327274A (en) * | 2011-09-02 | 2012-01-25 | 江苏京甲药业有限公司 | Adrenal cortical hormone compound preparation |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103876243A (en) * | 2012-12-21 | 2014-06-25 | 贵州天刺力食品科技有限责任公司 | Compound antioxidant |
| CN103876243B (en) * | 2012-12-21 | 2015-11-11 | 贵州天刺力食品科技有限责任公司 | Compound antioxidant |
| CN104352499A (en) * | 2014-09-18 | 2015-02-18 | 赵继红 | Drug combination for analgesia, anesthesia or drug rehabilitation |
| CN107668723A (en) * | 2017-10-19 | 2018-02-09 | 重庆师范大学 | A kind of plastic bottle L arabinose oral liquids easy to break and preparation method thereof |
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Application publication date: 20121121 |