CN1706391A - Terramycin suspension emulsion - Google Patents
Terramycin suspension emulsion Download PDFInfo
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- CN1706391A CN1706391A CN 200510011693 CN200510011693A CN1706391A CN 1706391 A CN1706391 A CN 1706391A CN 200510011693 CN200510011693 CN 200510011693 CN 200510011693 A CN200510011693 A CN 200510011693A CN 1706391 A CN1706391 A CN 1706391A
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- Prior art keywords
- terramycin
- suspension emulsion
- oxytetracycline
- polysorbate
- oleic acid
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- 239000000839 emulsion Substances 0.000 title claims abstract description 52
- 239000000725 suspension Substances 0.000 title claims abstract description 52
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- 229940063650 terramycin Drugs 0.000 title claims abstract description 37
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims abstract description 11
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- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims abstract description 11
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- 239000005642 Oleic acid Substances 0.000 claims abstract description 11
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims abstract description 11
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- 239000003963 antioxidant agent Substances 0.000 claims abstract description 9
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 9
- 238000003756 stirring Methods 0.000 claims abstract description 8
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- IWVCMVBTMGNXQD-UHFFFAOYSA-N terramycin dehydrate Natural products C1=CC=C2C(O)(C)C3C(O)C4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-UHFFFAOYSA-N 0.000 claims description 24
- 238000002360 preparation method Methods 0.000 claims description 17
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- 229960003912 probucol Drugs 0.000 claims description 9
- 230000002421 anti-septic effect Effects 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 229960002969 oleic acid Drugs 0.000 claims description 5
- 238000007789 sealing Methods 0.000 claims description 4
- IWVCMVBTMGNXQD-PXOLEDIWSA-N oxytetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-PXOLEDIWSA-N 0.000 claims 2
- 239000003814 drug Substances 0.000 abstract description 42
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- OWFJMIVZYSDULZ-PXOLEDIWSA-N (4s,4ar,5s,5ar,6s,12ar)-4-(dimethylamino)-1,5,6,10,11,12a-hexahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O OWFJMIVZYSDULZ-PXOLEDIWSA-N 0.000 description 24
- 239000004530 micro-emulsion Substances 0.000 description 21
- 229940079593 drug Drugs 0.000 description 18
- 238000002347 injection Methods 0.000 description 16
- 239000007924 injection Substances 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 239000003921 oil Substances 0.000 description 7
- 239000004094 surface-active agent Substances 0.000 description 7
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- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 241000005139 Lycium andersonii Species 0.000 description 1
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- HALQELOKLVRWRI-VDBOFHIQSA-N doxycycline hyclate Chemical compound O.[Cl-].[Cl-].CCO.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H]([NH+](C)C)[C@@H]1[C@H]2O.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H]([NH+](C)C)[C@@H]1[C@H]2O HALQELOKLVRWRI-VDBOFHIQSA-N 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
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- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229910000474 mercury oxide Inorganic materials 0.000 description 1
- UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 description 1
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- 210000000056 organ Anatomy 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- -1 place a mixing bowl Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
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- 230000006920 protein precipitation Effects 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
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- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 239000000273 veterinary drug Substances 0.000 description 1
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention is long acting terramycin suspension emulsion. The long acting terramycin suspension emulsion includes terramycin 20 wt%, oleic acid 3-8 wt%, polysorbate 3-8 wt%, propylene glycol 30-50 wt%, antioxidant 0.5 wt% and preservative 0.0006 wt% except water. The terramycin suspension emulsion is prepared through stirring process, and is yellow or brown and ropy. The terramycin suspension emulsion has slow release of the effective medicine component, high bioavailability, enhanced medicinal effect, long effective blood medicine concentration maintaining period up to 72 hr, low cost and other advantages.
Description
Technical field
The present invention relates to a kind of oxytetracycline pharmaceutical dosage form for the treatment of livestock and poultry and preparation method thereof, particularly prescription of terramycin suspension emulsion and preparation method thereof.
Background technology
The delivery system of medicine is one of hot research field of the world of medicine always.Microemulsion is a kind of novel delivery system, it is in proper proportion by surfactant, cosurfactant, oil and water, spontaneous formation a kind of evenly, low viscosity, thermodynamically stable transparent or semitransparent dispersion, this system has high stability and to the high dispersion and the absorbability of solute.The pharmaceutical preparation of using the microemulsion development can improve the infiltration rate of bioavailability of medicament and body, promote medicine in the intravital absorption of machine, increase the dissolubility of insoluble drug, strengthen stability of drug, and medicine is concentrated in target organs, strengthen the curative effect of medicine.Because microemulsion has many advantages, thereby enjoys people to pay close attention in recent years.
The preparation technology of microemulsion is simple, and key is to select suitable prescription, after having selected suitable prescription, oil, water, surfactant and cosurfactant is mixed stirring can form microemulsion.The foundation of option table surface-active agent when hydrophile-lipophile balance value is the preparation microemulsion, the w/o type microemulsion needs with the surfactant of HLB value in the 3-6 scope, and O/W type microemulsion needs with the surfactant of HLB value in the 8-18 scope; The ionic nature of surfactant also is one of key factor of decision microemulsion formation, cationic surface active agent is suitable in the medium of pH3-7 scope, anionic surfactant is applicable to the medium that pH8 is above, and nonionic surfactant all can use at the medium of pH3-10, and in addition, the size of oil phase molecule is to the formation of microemulsion also outbalance, the oil phase molecule volume is more little in principle, dissolving power is strong more, easy more formation microemulsion, the long formation microemulsion that then is difficult for of oil phase molecule chain.
Because microemulsion has the advantage of many uniquenesses, and its preparation can be used for various route of administration, and therefore, microemulsion formulation will be extensive day by day in the application of field of medicaments.At present, the more delivery system that is used for medicine of microemulsion, and existing many preparations are used for clinically, and the research of relevant microemulsion formulation is more abroad, and existing commercially produced product, and domestic many places are in conceptual phase.As disclosing the technology of microemulsion in the following document as the carrier of medicine:
[1] The Ministry of Agriculture of the People's Republic of China, MOA. vibramycin injection [M]. " import veterinary drug quality standard ", 1993,3-4.
[2] Xu Shixin, Guo Wenlin, Zhong Feng, etc. Ursocycline injection compares [J] Chinese veterinary drug magazine at pig body giving drugs into nose for kinetics, and 1998,32 (1): 10-13.
[3] Tang Lijuan. microemulsion delivery system [J]. foreign medical science-synthetic drug, biochemical medicine, preparation fascicle, 1988,9 (5): 294-296.
[4] Wang Hongxi. the progress of microemulsion formulation [J]. foreign medical science-pharmacy fascicle, 1996,23 (4): 206-211.
[5]Neumayer?HH，Farber?L，Haller?P，et?al.Clinicalexperience?transferring?kidney?transplant?patients?fromsandimmun?to?sandimmun?neoral-resultsafter?3months[J].ClinNephrol，1995，43(Suppl?1)：S27.
Oxytetracycline is the telracycline family broad ectrum antibiotic, gram positive bacteria, gram negative bacteria, rickettsia, chlamydia, mycoplasma and spirillum etc. all there are inhibitory action, can be used for preventing and treating Bacillus pasteurii disease, brucellosis, anthrax, escherichia coli and diseases such as Salmonella infection, glanders and mycoplasmal pneumonia of swine.Oxytetracycline belongs to soda acid both sexes crystal thing, can with bronsted lowry acids and bases bronsted lowry be combined into salt, in water dissolving atomic, be soluble in diluted acid and diluted alkaline, more stable in acidic aqueous solution, easily go to pot in the alkaline aqueous solution and lost efficacy.
At present, the dosage form of oxytetracycline preparation mainly contains powder, tablet, unguentum and injection, and wherein ejection preparation comprises: 5% conventional injection 0.5%,, 10%, 20% long-acting injection, 25% oil system suspension.Because conventional injection drug level is low, duration of efficacy is short, thereby exists injected dose big, and frequency injection is many, needs shortcomings such as injection 2 times/day, and therefore, people have explored the research of high-concentration long-acting ejection preparation.The external Ursocycline injection of having succeeded in developing in the eighties, its commodity specially good effect rice by name with long-acting earlier, and import China.In recent years, the domestic high concentration Ursocycline injection that also has been developed into is to adopt different solvents such as polyvinylpyrrolidone, alpha-pyrrolidone, propylene glycol to make.
Though it is few that injection and oil system suspension have injected dose, keep the body effective blood drug concentration for a long time, advantages such as the medication number of times is few, but also there is shortcoming in various degree, as medicine cost height, poor stability, complex manufacturing, the injection that the solvent that has the is made injection shortcomings such as 2 times/day of still needing.
Summary of the invention
Primary and foremost purpose of the present invention is to provide a kind of terramycin suspension emulsion that utilizes microemulsion system as the oxytetracycline delivery system at the problems referred to above.
Another purpose of the present invention is to provide a kind of preparation method of terramycin suspension emulsion.
For realizing the object of the invention, terramycin suspension emulsion of the present invention comprises the component in weight ratio: 20 parts of oxytetracyclines, oleic acid 3-8 part, Polysorbate 3-8 part, Probucol 30-50 part, 0.5 part of antioxidant, 0.006 part of antiseptic add water to 100 parts.
The production method of terramycin suspension emulsion of the present invention comprises step: prepare component by weight: 20 parts of oxytetracyclines, oleic acid 3-8 part, Polysorbate 3-8 part, Probucol 30-50 part, 0.5 part of antioxidant, 0.006 part of antiseptic and add to 100 parts water; Measure Polysorbate, oleic acid, Probucol, place a mixing bowl mix homogeneously by prescription; Slowly add entry, and constantly stir until mixing; Add oxytetracycline, antioxidant and the antiseptic of recipe quantity, stir, filled with solution, the sealing that is obtained is the terramycin suspension emulsion finished product.
Terramycin suspension emulsion of the present invention is as the telracycline family broad ectrum antibiotic new formulation of treatment livestock and poultry, is to have utilized microemulsion to form theory and use conventional paddling process and a kind of long-acting slow-release preparation of preparing.Because it is to utilize the delivery system of microemulsion system as oxytetracycline, therefore compare institute has the following advantages with conventional oxytetracycline injection: can reduce the medication number of times, reduce drug cost, simplify production technology, increase drug targeting, improve the infiltration rate of bioavailability of medicament and body, strengthen the curative effect of medicine.In addition, the preparation of terramycin suspension emulsion of the present invention does not need special solvent, so cost is low, production technology simple, be easy to realize industrialization.
The specific embodiment
Embodiment 20% terramycin suspension emulsion
Fetch earth mycin 20g, oleic acid 5g, Polysorbate 5g, Probucol 40g, antioxidant 0.5g, antiseptic 0.006g is standby, and oxytetracycline, oleic acid, Polysorbate are carried out sterilization treatment; Get recipe quantity oleic acid, Polysorbate, Probucol, place a mixing bowl, mix homogeneously; Slowly add distilled water to 100ml, and constantly stir until mixing; Add oxytetracycline, antioxidant and the antiseptic of recipe quantity, stir; The filled with solution, the sealing that are obtained are the terramycin suspension emulsion finished product.
The quality stability test of terramycin suspension emulsion
1, physical behavior
20% terramycin suspension emulsion is yellow to yellowish-brown, heavy-gravity slightly Emulsion, has layering after leaving standstill for a long time, and supernatant be that yellow lower floor is a yellow mercury oxide to filemot liquid, the vibration back be uniform yellow to the yellowish-brown emulsion, medicinal liquid pH is 3-4.
2, medicine assay
(1) drafting of working curve
Accurately take by weighing oxytetracycline reference substance 10mg, place the 100ml volumetric flask, hydrochloric acid solution with 0.1mol/L is diluted to scale, making oxytetracycline concentration is 100 μ g/ml storing solutions, essence is got storing solution and is split in right amount in the 100mL volumetric flask again, hydrochloric acid solution with 0.1mol/L is diluted to scale, makes the titer that concentration is 2,4,6,8,10,12,15,17 μ g/ml, measures trap at 268nm wavelength place.Oxytetracycline concentration is in 4-15 μ g/ml scope as a result, and trap and concentration are good linear relationship, with absorption value A value the concentration C value is returned, and gets regression equation C=24.0904A+0.2406, r=0.9998.
(2) determination of recovery rates
Preparation concentration is respectively 190,195,200 and four kinds of terramycin suspension emulsions of 205mg/ml, divide the suspension emulsion of getting variable concentrations an amount of, hydrochloric acid solution dilution with 0.1mol/L, the concentration that makes oxytetracycline is in 4-15 μ g/ml scope, the place measures the trap of each concentration sample at the 268nm wavelength, and calculates its response rate.Its average recovery rate is 100.62% as a result, and RSD is 0.48%.
(3) medicine assay
Randomly draw 5 bottles of the terramycin suspension emulsions of 5 batches of different holding times, accurately pipette 1.0ml suspensoid sample respectively, hydrochloric acid solution with 0.1mol/L is diluted to the solution that oxytetracycline concentration is 10 μ g/ml, hydrochloric acid solution with 0.1mol/L is made blank, measure the trap of dilute sample supernatant at 268nm wavelength place, by the content of oxytetracycline in the regression equation calculation suspensoid sample.The oxytetracycline content that the result measures is respectively 99.79%, 98.46%, 100.75%, 100.82%, 99.90% of actual amount, conforms to quality requirements.
3, stability test
(1) viscosimetric analysis
The conveying end internal diameter is 1.2mm, internal diameter suitable for reading is the 1ml glass pipette of 2.7mm, draw the suspension emulsion 1ml of different batches respectively, at ambient temperature, the record microemulsion vertically drops to the 0.4ml scale from the 1ml scale, promptly flow out the needed time of 0.4ml suspension emulsion (s), the viscosity of suspension emulsion is 3-4s as a result.
(2) acceleration by light test
The terramycin suspension emulsion sample of different batches with preparation, be sub-packed in the water white vial, after the sealing, put illuminance and be in the environment about 4500LX and place 10d, and place 0,5,7,10d takes sample, observe character, the medicine flocculation situation of terramycin suspension emulsion and measure settling volume ratio, size of pharmaceutical particles, medicament contg.3 batch mixing suspension emulsion samples have the intensification slightly except that supernatant fluid color as a result, and other character there is no significant change as the pH value of suspension emulsion, settling volume than indexs such as, size of pharmaceutical particles and medicament contgs, shows that suspension emulsion has stability to light.
(3) heating and moistening test
The terramycin suspension emulsion sample of different batches with preparation, place in the water-jacket typ electro-heating standing-temperature cultivator, adjusting the incubator temperature is 30 ± 1 ℃, relative humidity is 60% ± 5%, routine observation 3 months, sampling in every month 1 time is checked physical behavior, settling volume ratio, medicine flocculation situation, the granular size of terramycin suspension emulsion sample, and is measured medicament contg.Suspension emulsion sample routine observation is 3 months as a result, and its quality index there is no significant change, and terramycin suspension emulsion having good stability to temperature, humidity is described.
(4) heavy dispersibility
In room temperature environment, behind the static placement of terramycin suspension emulsion 30d, firmly vibrate up and down for several times, check heavy dispersibility, physical behavior, the flocculability of suspension emulsion then, the result shows that terramycin suspension emulsion through 3-5 vibration, gets final product homodisperse, and the bottle end does not have precipitation, do not have grumeleuse in the suspensoid, the property of heavily loosing of suspensoid is good.
4, syringeability
After the mycin suspension emulsion that the fetches earth vibration evenly, extract the suspensoid sample with the 6-10 syringe needle respectively, measure complexity and speed that the different model syringe needle extracts suspensoid, the result is except that extracting speed than slow with No. 6 syringe needles, all the other 7-10 syringe needles all can extract suspension emulsion smoothly, and this explanation suspension emulsion has good syringeability.
5, diameter of aspirin particle is measured
Use microscopic method and measure oxytetracycline grain diameter shape, size and distribution.The mycin suspension emulsion sample that fetches earth fully shakes up with 100 times of dilutions of distilled water, gets 1 dilute sample and drips on microscope slide, observes the shape of oxytetracycline microgranule, the size and the distribution of mensuration microgranule under 400 times of visuals field.Oxytetracycline microgranule in the visible suspension emulsion of microscopy is spherical in shape, the granule of size between 2-5 μ m accounts for more than 96% of medicine sum, the crystal formation unanimity, and the size relative scale meets normal distribution, the suspensoid room temperature is placed 30d, does not see the drug particles growth, makes the transition and condenses phenomenon.The oxytetracycline microgranule of not making suspensoid is a long column shape, and the granule of size between 2-3 * 35-95 μ m accounts for more than 90% of medicine sum.
6, pharmacokinetics test
(1) experimental animal
Experimental animal is the healthy Harbin white pig of 5 body weight 30-50kg, raises in a conventional manner, does not add any medicine in the feedstuff.
(2) administrated method
A deep part muscle shot 20% terramycin suspension emulsion 0.1ml/kg body weight is promptly injected oxytetracycline 20mg/kg body weight behind the pig ear.
(3) blood specimen collection
After medication 1,2,4,8,12,24,36,48,60,72h takes blood sample 5ml respectively, injects the centrifuge tube that 1% heparin is housed, the centrifugal 15min of 3000r/min, preparation blood plasma is put-20 ℃ of refrigerators and is preserved to be measured.
(4) determination of plasma concentration
Get blood plasma 1ml, add 20% trichloroacetic acid 0.25ml, protein precipitation is put-4 ℃ of refrigerator cold-storage 15min, the centrifugal 15min of 4000r/min, it is an amount of to draw supernatant, after activatory C18 post, after waiting to flow to end, the washing of water 1-2ml cleaning mixture is neutral to effluent, dries up.With the above elution samples of eluent, collect eluent, get 20 μ l high-pressure liquid chromatographies.
With sample determination gained peak area substitution regression equation, calculate the oxytetracycline concentration in the Solid-Phase Extraction eluent, calculate blood drug level C (the μ g/ml)=X * V of different time blood sample after the injection then by following formula
2* V
4/ V
1* V
3* R.
(5) determination of plasma concentration result
Different time behind injection 20% terramycin suspension emulsion, the determination of plasma concentration of Sanguis sus domestica sample the results are shown in Table 1.
Table 1 20% terramycin suspension emulsion is at the intravital blood drug level of pig (μ g/ml)
| Time (h) | ??1 | ??2 | ??4 | ??8 | ??12 | ??24 | ??36 | ??48 | ??60 | ??72 |
| Mean concentration | ??2.14 | ??3.39 | ??3.30 | ??3.00 | ??1.53 | ??1.10 | ??0.99 | ??0.81 | ??0.60 | ??0.48 |
| ??±SD | ??0.70 | ??0.58 | ??0.54 | ??0.21 | ??0.39 | ??0.05 | ??0.58 | ??0.12 | ??0.54 | ??0.24 |
0.5 μ g/ml is a minimum effective drug concentration with blood plasma oxytetracycline concentration, and as known from Table 1, the time that 20% terramycin suspension emulsion can be kept effective blood drug concentration is 72h, therefore, by injection in per 3 days once, can reach desirable curative effect.
This shows that 20% terramycin suspension emulsion medication post-absorption is slow, but the significant prolongation curative effect, the time that a drug can be kept effective blood drug concentration is 72h, medication in per 3 days gets final product for 1 time.
Claims (3)
1. terramycin suspension emulsion comprises the component in weight ratio: 0.0006 part of 20 parts of oxytetracyclines, oleic acid 3-8 part, Polysorbate 3-8 part, Probucol 30-50 part, 0.5 part of antioxidant and antiseptic add water to 100 parts.
2. terramycin suspension emulsion as claimed in claim 1, wherein said oleic acid are 5 parts, and described Polysorbate is 5 parts, and described Probucol is 40 parts.
3. the preparation method of terramycin suspension emulsion as claimed in claim 1 or 2 is characterized in that may further comprise the steps:
(1) prepares oxytetracycline, oleic acid, Polysorbate, Probucol, antioxidant, antiseptic and water according to described proportioning;
(2) measure Polysorbate, oleic acid, Probucol by prescription and place a mixing bowl mix homogeneously;
(3) slowly add entry, and constantly stir until mixing;
(4) oxytetracycline, antioxidant and the antiseptic of adding recipe quantity stir;
(5) filled with solution, the sealing that obtains is the terramycin suspension emulsion finished product.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105353096A (en) * | 2015-10-13 | 2016-02-24 | 中国农业大学 | Apparatus for determining needle passing performance of injection |
| EP3624840A4 (en) * | 2017-05-19 | 2021-03-10 | Lunella Biotech, Inc. | Antimitoscins: targeted inhibitors of mitochondrial biogenesis for eradicating cancer stem cells |
| US11497759B2 (en) | 2017-12-01 | 2022-11-15 | Lunella Biotech, Inc. | Repurposcins: targeted inhibitors of mitochondrial biogenesis for eradicating cancer stem cells |
-
2005
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105353096A (en) * | 2015-10-13 | 2016-02-24 | 中国农业大学 | Apparatus for determining needle passing performance of injection |
| EP3624840A4 (en) * | 2017-05-19 | 2021-03-10 | Lunella Biotech, Inc. | Antimitoscins: targeted inhibitors of mitochondrial biogenesis for eradicating cancer stem cells |
| US11160821B2 (en) | 2017-05-19 | 2021-11-02 | Lunella Biotech, Inc. | Antimitoscins: targeted inhibitors of mitochondrial biogenesis for eradicating cancer stem cells |
| US11865130B2 (en) | 2017-05-19 | 2024-01-09 | Lunella Biotech, Inc. | Antimitoscins: targeted inhibitors of mitochondrial biogenesis for eradicating cancer stem cells |
| US11497759B2 (en) | 2017-12-01 | 2022-11-15 | Lunella Biotech, Inc. | Repurposcins: targeted inhibitors of mitochondrial biogenesis for eradicating cancer stem cells |
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