CN101703466A - Borneol injection and preparation method thereof - Google Patents
Borneol injection and preparation method thereof Download PDFInfo
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- CN101703466A CN101703466A CN200910186560A CN200910186560A CN101703466A CN 101703466 A CN101703466 A CN 101703466A CN 200910186560 A CN200910186560 A CN 200910186560A CN 200910186560 A CN200910186560 A CN 200910186560A CN 101703466 A CN101703466 A CN 101703466A
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Abstract
The invention provides a borneol injection and a preparation method thereof. The method solves the technical bottle-neck of the injection caused by that borneol is not dissolved in water, greatly improves the storage stability of the borneol injection and obtains the borneol injections (aqueous injections, powder injections and transfusion injections) with proper concentration and stable storage.
Description
Technical field
The present invention relates to the formulation method of Borneolum Syntheticum injection.
Background technology
Borneolum Syntheticum roughly can be divided into natural Broneolum Syntheticum and adopt the synthetic BORNEOLUM SYNTHETICUM of chemical method.Wherein, natural Broneolum Syntheticum is the fresh branch of canella Camphor tree Cinnamomumcamphora (L.) Presl, the crystallization that leaf is processed into through extraction, the main component of natural Broneolum Syntheticum is dextro Borneolum Syntheticum (its percentage by weight is generally more than 90%), therefore, natural Broneolum Syntheticum also claims natural dextro Borneolum Syntheticum, Borneolum Syntheticum, Flos Mume brain, borneol etc.; BORNEOLUM SYNTHETICUM is a racemization mixing Borneolum Syntheticum, and many at present employing Oleum Terebinthinaes, Camphora etc. are synthetic through chemical method.
The main effect of Borneolum Syntheticum is the refreshment of having one's ideas straightened out, clearing away heat to alleviate pain, can be used for the treatment of or alleviate symptoms such as calentura coma, convulsion are fainted, apoplexy syncope due to accumulation of phlegm, infantile convulsion expectorant fan, sore throat toothache, aphtha carbuncle and ulcer, conjunctival congestion, clinically diseases such as brains pain, throat ability to speak swell and ache, chronic bronchitis, scald that are used for the treatment of more, also Chang Zuowei " priming " or " adjuvant drug " and other drug compatibility agent, the medical value height.
At present, because the reason of Borneolum Syntheticum poorly water-soluble (almost insoluble in water), be that the pharmaceutical preparation of principal agent thing composition is considerably less with the Borneolum Syntheticum.At present commercial buy have only the Borneolum Syntheticum oral solid formulation basically, and adopt oral route of administration and solid dosage forms, the absorption that causes Borneolum Syntheticum slowly and bioavailability very low.
In general, adopt the mode of drug administration by injection better than the drug effect of oral administration, bioavailability is higher.That can adopt that the injection type of drug administration by injection mode comprises that medicine is mixed with can directly inject intravital sterile solution (generally claiming infusion solution) or medicine is mixed with for the sterilized powder (injectable powder) or the concentrated solution (aqueous injection) of facing with preceding wiring solution-forming or suspension.
Yet for the relatively poor medicine of dissolubility, it is very harsh to adopt the drug administration by injection mode that the stability of the method for the selection of concrete dosage form selection, solvent and drug level, preparation, the pharmaceutical preparation that makes etc. is required, therefore, at present be that the ejection preparation of principal agent thing composition can't be succeedd always with the Borneolum Syntheticum.For example, once the someone proposed employing Borneolum Syntheticum lipidosome injection type, but technology is very complicated, and the cost height is difficult to use on industry; In addition, can satisfy the solvent of injection selects very limited, in order to save cost consideration, the general water for injection (general most solvents are water for injection during transfusion) that adopts, and Borneolum Syntheticum is almost insoluble in water, be difficult to obtain the Borneolum Syntheticum injection type that Borneolum Syntheticum concentration has reached treatment valid density (at human body), even adopt other modes to improve the concentration of Borneolum Syntheticum, but the non-constant of bin stability of the Borneolum Syntheticum injection that obtains, infusion solution or aqueous injection be long-time to be placed and has crystal and separate out, and the injectable powder period of storage is long to be caused injection to face with preceding difficulty to dissolve with water for injection easily.
To sum up, there is urgent demand this area for the Borneolum Syntheticum injection (aqueous injection, injectable powder, infusion solution) that acquisition reaches suitable concn and stable storage.
Summary of the invention
The invention provides a kind of formulation method of Borneolum Syntheticum injection, described injection is aqueous injection, injectable powder or infusion solution, and this method mainly may further comprise the steps:
1) get an amount of cosolvent dissolving Borneolum Syntheticum, obtaining Borneolum Syntheticum concentration is the concentrated wiring liquid of 0.1g/L～50g/L; Or get an amount of cosolvent dissolving Borneolum Syntheticum and make suspension, more while stirring to wherein adding water for injection gradually to forming the concentrated wiring liquid that Borneolum Syntheticum concentration is 0.1g/L～50g/L;
Described cosolvent is that propylene glycol, ethanol, glycerol, polysorbate, Polyethylene Glycol, benzyl benzoate, mass percent are not less than one or more the mixture in the aqueous solution for injection of 0.1% HP-;
2) concentrated wiring liquid that step 1) is obtained with water for injection by volume multiple be diluted to 2～3000 times;
3) to step 2) dilute solution that obtains carries out the activated carbon adsorption operation;
4) to completing steps 3) solution in add the agent of injection pH regulator, pH value is transferred to 3.5～6.5;
5) solution that step 4) is obtained leaves standstill 1h～72h 1 ℃～8 ℃ following cold preservations, again it is carried out the fine straining sterilization.
In the technique scheme, described injection is aqueous injection, injectable powder or infusion solution.What described infusion solution was meant that Borneolum Syntheticum is mixed with can directly inject intravital sterile solution; Described aqueous injection is meant Borneolum Syntheticum is mixed with for facing with the aseptic concentrated solution that before is made into injection; Described aqueous injection is meant Borneolum Syntheticum is mixed with for facing with the sterilized powder that before is made into injection.
In the technique scheme, described water for injection is the common technology term of this area, is generally distilled water or the deionization water through the distillation gained, and its preparation method is well known to those skilled in the art.
In a specific embodiments of the present invention, step 2) dilution step preferably adopts and adds water for injection while stirring, carries out volume quantitative at last.
In the technique scheme, the activated carbon adsorption of step 3) is operating as the routine operation in the injection preparation well-known to those skilled in the art, and it mainly acts on the thermal source that is to remove in the solution.In a specific embodiment of the present invention, to step 2) add an amount of needle-use activated carbon in the dilute solution that obtains, adsorbed about 20 minutes, filter decarburization afterwards.
In a specific embodiments of the present invention, the fine straining sterilization of step 5) employing aperture is that the microporous filter membrane of 0.22 μ m filters.
In the technique scheme, carry out preparation routine operations such as correspondingly fill, sterilization, lamp inspection respectively at concrete injection type again after the step 5), finally obtain product.
Preferably, if described injection is aqueous injection, step 2) in, the concentrated wiring liquid that step 1) is obtained with water for injection by volume multiple is diluted to 8～15 times.
Preferably, if described injection is injectable powder, step 2) in, the concentrated wiring liquid that step 1) is obtained with the water for injection that has dissolved the injection excipient by volume multiple is diluted to 8～15 times; Described injection excipient can be selected one or more the mixture in mannitol, lactose, gelatin hydrolysate, dextran, polyvinylpyrrolidone, glucose, the fructose; And the injection excipient is in step 2) concentration in the dilute solution that obtains is 1g/L～500g/L.If the preparation injectable powder, injectable powder preparation routine operations such as in general, the solution that also needs after the step 5) to obtain carries out fill, jumps a queue, lyophilization, gland, lamp inspection finally obtain the injectable powder product.
Preferably, if described injection is infusion solution, step 2) in, the concentrated wiring liquid that step 1) is obtained with the water for injection that has dissolved the injection osmotic pressure regulator by volume multiple is diluted to 800～2000 times; Described injection osmotic pressure regulator can selective chlorination sodium, a kind of in potassium chloride, magnesium chloride, glucose, xylitol, sorbitol or the dextran.Wherein, step 2) dilute the concentration of the ultimate density of osmotic pressure regulator in the solution that obtains for suitable injection, those skilled in the art can select as the case may be.
Preferably, the agent of described injection pH regulator can be selected one or more in hydrochloric acid, sodium hydroxide, sodium bicarbonate, sodium citrate, the citric acid.
Preferably, the dextro Borneolum Syntheticum composition is further preferred greater than 90%. in the described Borneolum Syntheticum, and described Borneolum Syntheticum is a natural Broneolum Syntheticum.
Adopt the Borneolum Syntheticum injection formulation method of technique scheme, on the one hand, the inventor has screened through a large amount of experimental studies severally can dissolve the cosolvent that disperses Borneolum Syntheticum in other words effectively and can dissolve each other with water especially effectively, after having found that the above-mentioned several specific cosolvent of first usefulness dissolves dispersion to Borneolum Syntheticum, add again and do not have solid when water for injection dilutes and separate out, adopt this mode, the Borneolum Syntheticum injection type that has obtained various suitable concns is (with the aqueous injection of Borneolum Syntheticum, injectable powder, the suitable concn of infusion solution correspondence), solved the water insoluble technical bottleneck that ejection preparation is brought of Borneolum Syntheticum dexterously; On the other hand, it also is the most key part of technical solution of the present invention, the operation that in the preparation process of injection some must be carried out, as activated carbon adsorption, meetings such as fine straining degerming damage (when especially preparing aqueous injection and injectable powder) to the stability of solution system, during operation or long-time the placement have solid and separate out, yet the inventor finds through great deal of experimental, on the basis of regulating suitable pH value, and before fine straining, Borneolum Syntheticum solution is carried out cold preservation to leave standstill processing and (leaves standstill 1h～72h) 1 ℃～8 ℃ following cold preservations, improved the bin stability of Borneolum Syntheticum injection greatly, avoided Borneolum Syntheticum aqueous injection or infusion solution to place for a long time producing that problem that solid separates out and Borneolum Syntheticum powder injection are long-time places that to cause facing timing difficult with the dissolved problem of water for injection, obtained beyond thought technique effect.
The present invention also provides the Borneolum Syntheticum injection that adopts above-mentioned formulation method to make.
The specific embodiment
Below in conjunction with specific embodiment the present invention is further specified.
Embodiment 1:
1) gets natural Broneolum Syntheticum powder 10g (wherein the quality percentage composition of dextro Borneolum Syntheticum is about 97%～99%), after adding the 5ml dissolve with ethanol, slowly (mass percent is about 3% to the water for injection saturated solution that wherein adds hydroxypropyl hydroxy propyl-Beta-ring paste, added 300ml altogether), stir while adding to solution and clarify; 2) in the solution that step obtains, slowly add water for injection more while stirring and dilute, with volume quantitative to 10000ml (be about to volume dilution to 33 times); 3) add needle-use activated carbon 5g absorption 20 minutes, filtering decarbonization; 4) be adjusted to pH5.0 with hydrochloric acid solution; 5) step 4) is obtained solution sealing after, place 2 ℃ of following cold preservations to leave standstill 12 hours, use 0.22 μ m microporous filter membrane fine straining afterwards; Logical at last nitrogen fill is sealed to the 5ml glass ampule, sterilizes 30 minutes for 115 ℃, and lamp inspection promptly gets Borneolum Syntheticum injection hydro-acupuncture preparation (injection with small volume).
Embodiment 2:
Get natural Broneolum Syntheticum powder 10g (wherein the quality percentage composition of dextro Borneolum Syntheticum is about 96%～98%), add the dissolving of 800g propylene glycol and make suspension, add the injection water to 1000ml, the stirring and dissolving clarification; Slowly join in the water for injection while stirring again, add injection and blunge dissolving, add needle-use activated carbon 5g absorption 20 minutes also quantitatively to 10000ml, filtering decarbonization, be adjusted to pH4.0 with hydrochloric acid solution, sealing, cold preservation was left standstill 12 hours, with 0.22 μ m microporous filter membrane fine straining, logical nitrogen fill is sealed to the 2ml glass ampule, sterilizes 30 minutes for 115 ℃, lamp inspection promptly gets Borneolum Syntheticum injection hydro-acupuncture preparation (injection with small volume).
Embodiment 3:
Get BORNEOLUM SYNTHETICUM powder 10g (wherein the quality percentage composition of dextro Borneolum Syntheticum is about 45%～60%), add the little heated and stirred dissolving of 500g glycerol, slowly join in the water for injection while stirring again, add injection and blunge dissolving also quantitatively to 10000ml, add needle-use activated carbon 5g absorption 20 minutes, filtering decarbonization, be adjusted to pH5.0 with citric acid solution, sealing, cold preservation was left standstill 12 hours, with 0.22 μ m microporous filter membrane fine straining, logical nitrogen fill is sealed to the 5ml glass ampule, sterilizes 30 minutes for 115 ℃, lamp inspection promptly gets Borneolum Syntheticum injection hydro-acupuncture preparation (injection with small volume).
Embodiment 4:
Get natural Broneolum Syntheticum powder 10g (wherein the quality percentage composition of dextro Borneolum Syntheticum is about 95%～98%), add the 100g tween 80, the 400g propylene glycol, add the injection water to the 1000ml stirring and dissolving, slowly join in the water for injection while stirring again, add injection and blunge dissolving also quantitatively to 10000ml, add needle-use activated carbon 5g absorption 20 minutes, filtering decarbonization is adjusted to pH5.0 with citric acid solution, sealing, cold preservation was left standstill 12 hours, and with 0.22 μ m microporous filter membrane fine straining, logical nitrogen fill is to the 2ml glass ampule, seal, sterilized 30 minutes for 115 ℃, lamp inspection promptly gets Borneolum Syntheticum injection hydro-acupuncture preparation (injection with small volume).
Embodiment 5:
Get natural Broneolum Syntheticum powder 10g (wherein the quality percentage composition of dextro Borneolum Syntheticum is about 96%～99%), adding is stuck with paste with 300g hydroxypropyl hydroxy propyl-Beta-ring and is mixed with in the saturated injection of aqueous solution, stirs to make the solution clarification; Get mannitol 250g and add the water for injection dissolving, slowly add the Borneolum Syntheticum concentrated wiring liquid while stirring, add injection and blunge dissolving also quantitatively to 10000ml, add needle-use activated carbon 10g absorption 20 minutes, filtering decarbonization is adjusted to pH5.0 with hydrochloric acid solution, sealing, cold preservation was left standstill 12 hours, with 0.22 μ m microporous filter membrane aseptic filtration, fill is to cillin bottle, and every bottled 5ml jumps a queue, lyophilization, gland, lamp inspection promptly gets the Borneolum Syntheticum injection powder injection.
Embodiment 6:
Get natural Broneolum Syntheticum powder 10g (wherein the quality percentage composition of dextro Borneolum Syntheticum is about 98%～99%), add the little heated and stirred dissolving of 500g glycerol, stir adding water for injection to 1000ml; Get lactose 250g and add the water for injection dissolving, slowly add the Borneolum Syntheticum concentrated wiring liquid while stirring, add injection and blunge dissolving also quantitatively to 10000ml, add needle-use activated carbon 10g absorption 20 minutes, filtering decarbonization is adjusted to pH4.5 with citric acid solution, sealing, cold preservation was left standstill 12 hours, with 0.22 μ m microporous filter membrane aseptic filtration, fill is to cillin bottle, and every bottled 5ml jumps a queue, lyophilization, gland, lamp inspection promptly gets the Borneolum Syntheticum injection powder injection.
Embodiment 7:
Get natural Broneolum Syntheticum powder 10g (wherein the quality percentage composition of dextro Borneolum Syntheticum is about 96%～97%), add 20g poloxamer 188, the 400g propylene glycol, add the injection water to the 1000mL stirring and dissolving, slowly join in the water for injection while stirring again, add injection and blunge dissolving also quantitatively to 10000mL, add pin with activated carbon 5g absorption 20min, filter decarburization, be adjusted to pH5.0 with citric acid solution, sealing, cold preservation was left standstill 12 hours, and with 0.22 μ m microporous filter membrane fine straining, logical nitrogen fill is to 2mL glass ampere, seal, sterilized 30 minutes for 115 ℃, lamp inspection promptly gets Borneolum Syntheticum injection hydro-acupuncture preparation (injection with small volume).
Embodiment 8:
Get natural Broneolum Syntheticum powder 10g (wherein the quality percentage composition of dextro Borneolum Syntheticum is about 96%～98%), add an amount of dissolve with ethanol after, slowly add to stick with paste and be mixed with in the saturated injection of aqueous solution with 300g hydroxypropyl hydroxy propyl-Beta-ring, stir and make the solution clarification; Heat-obtaining water for injection 500L, add sodium chloride 9000g, needle-use activated carbon 250g, stirring makes dissolving evenly and boil 30min, is cooled to 40～50 ℃, returns filter 10 minutes, take off charcoal, slowly add the Borneolum Syntheticum concentrated wiring liquid while stirring, add injection and blunge dissolving, add needle-use activated carbon 250g absorption 20 minutes also quantitatively to 1000L, filtering decarbonization, be adjusted to pH5.5 with hydrochloric acid solution, sealing, cold preservation was left standstill 12 hours, with 0.22 μ m microporous filter membrane fine straining, logical nitrogen fill is sealed to the 500ml infusion bottle, sterilizes 30 minutes for 115 ℃, lamp inspection promptly gets Borneolum Syntheticum injection infusion preparation (high-capacity injection).
Embodiment 9:
Get natural Broneolum Syntheticum powder 10g (wherein the quality percentage composition of dextro Borneolum Syntheticum is about 95%～98%), after the dissolving of adding 800g propylene glycol, add the injection water to 1000ml, the stirring and dissolving clarification; Heat-obtaining water for injection 500L, add glucose 50000g, needle-use activated carbon 250g, stirring makes dissolving evenly and boil 30min, is cooled to 40～50 ℃, returns filter 10 minutes, take off charcoal, slowly add the Borneolum Syntheticum concentrated wiring liquid while stirring, add injection and blunge dissolving, add needle-use activated carbon 250g absorption 20 minutes also quantitatively to 1000L, filtering decarbonization, be adjusted to pH6.0 with citric acid solution, sealing, cold preservation was left standstill 12 hours, with 0.22 μ m microporous filter membrane fine straining, logical nitrogen fill is sealed to the 250ml infusion bottle, sterilizes 30 minutes for 115 ℃, lamp inspection promptly gets Borneolum Syntheticum injection infusion preparation (high-capacity injection).
Embodiment 10:
Get natural Broneolum Syntheticum powder 10g (wherein the quality percentage composition of dextro Borneolum Syntheticum is about 95%～98%), add the little heated and stirred dissolving of 500g glycerol, add the injection water to 1000ml, the stirring and dissolving clarification; Heat-obtaining water for injection 500L, add glucose 25000g, sodium chloride 4500g, needle-use activated carbon 250g, stirring makes dissolving evenly and boil 30min, is cooled to 40～50 ℃, returns filter 10 minutes, take off charcoal, slowly add the Borneolum Syntheticum concentrated wiring liquid while stirring, add injection and blunge dissolving, add needle-use activated carbon 250g absorption 20 minutes also quantitatively to 1000L, filtering decarbonization, be adjusted to pH5.2 with hydrochloric acid solution, sealing, cold preservation was left standstill 12 hours, with 0.22 μ m microporous filter membrane fine straining, logical nitrogen fill is sealed to the 100ml infusion bottle, sterilizes 30 minutes for 115 ℃, lamp inspection promptly gets Borneolum Syntheticum injection infusion preparation (high-capacity injection).
Embodiment 11
The technology gained injection that adopts cold preservation to leave standstill the technology of after-filtration and do not adopt cold preservation to leave standstill is carried out following controlled trial:
The Borneolum Syntheticum injection liquid drugs injection system that reference examples 1: embodiment 2 makes;
Reference examples 2: do not adopt cold preservation to leave standstill the Borneolum Syntheticum injection of the technology of after-filtration, removed cold preservation and left standstill operation, other are with embodiment 2, and the Borneolum Syntheticum that makes is injected liquid drugs injection system;
Above-mentioned two groups of preparations are carried out accelerated test investigate stability of drug products: under 40 ℃ ± 2 ℃ condition, carry out test in 6 months.Detect the investigation index in the 0th, 1,2,3,6 sampling at the end of month of duration of test.The investigation index comprises: test sample content, clarity test, pyrogen test, sterility test, pH mensuration etc.Investigation is the result show: under the accelerated test condition, every index of reference examples 1 and reference examples 2 is all qualified, and indistinction.
Immediately two groups of preparations are carried out long term test, get three batch samples and under 25 ℃ ± 2 ℃ conditions, test, sampling time point in 1 year be the every three months end once, 1 year per 6 the end of month, once later annual end was once.Long-term test results shows that after 1 year, the natural Broneolum Syntheticum content of reference examples 2 descends (concrete numerical value sees the following form) with this storage condition placement, and visible crystals is separated out simultaneously.Except that changes of contents, all the other indexs do not have obvious difference.
From above controlled trial as can be seen, Borneolum Syntheticum solution is carried out cold preservation leave standstill processing, improved the bin stability of Borneolum Syntheticum injection greatly, avoided the Borneolum Syntheticum aqueous injection to place for a long time and produced the problem that solid is separated out.
The present invention is not limited to the foregoing description, and all equivalences of doing according to inventive concept of the present invention, spirit change or modify, and all should be encompassed in protection scope of the present invention.
Claims (7)
1. the formulation method of a Borneolum Syntheticum injection, described injection is aqueous injection, injectable powder or infusion solution, this method mainly may further comprise the steps:
1) get an amount of cosolvent dissolving Borneolum Syntheticum, obtaining Borneolum Syntheticum concentration is the concentrated wiring liquid of 0.1g/L～50g/L; Or get an amount of cosolvent dissolving Borneolum Syntheticum and make suspension, more while stirring to wherein adding water for injection gradually to forming the concentrated wiring liquid that Borneolum Syntheticum concentration is 0.1g/L～50g/L;
Described cosolvent is that propylene glycol, ethanol, glycerol, polysorbate, Polyethylene Glycol, benzyl benzoate, mass percent are not less than one or more the mixture in the aqueous solution for injection of 0.1% HP-;
2) concentrated wiring liquid that step 1) is obtained with water for injection by volume multiple be diluted to 2～3000 times;
3) to step 2) dilute solution that obtains carries out the activated carbon adsorption operation;
4) to completing steps 3) solution in add the agent of injection pH regulator, pH value is transferred to 3.5～6.5;
5) solution that step 4) is obtained leaves standstill 1h～72h 0 ℃～8 ℃ following cold preservations, again it is carried out the fine straining sterilization.
2. formulation method as claimed in claim 1 is characterized in that: if described injection is aqueous injection, step 2) in, the concentrated wiring liquid that step 1) is obtained with water for injection by volume multiple is diluted to 8～15 times.
3. formulation method as claimed in claim 1 is characterized in that: if described injection is injectable powder, step 2) in, the concentrated wiring liquid that step 1) is obtained with the water for injection that has dissolved the injection excipient by volume multiple is diluted to 8～15 times;
Described injection excipient is one or more the mixture in mannitol, lactose, gelatin hydrolysate, dextran, polyvinylpyrrolidone, glucose, the fructose; And the injection excipient is in step 2) concentration in the dilute solution that obtains is 1g/L～500g/L.
4. formulation method as claimed in claim 1 is characterized in that: if described injection is infusion solution, step 2) in, the concentrated wiring liquid that step 1) is obtained with the water for injection that has dissolved the injection osmotic pressure regulator by volume multiple is diluted to 800～2000 times;
Described injection osmotic pressure regulator is a kind of in sodium chloride, potassium chloride, magnesium chloride, glucose, xylitol, sorbitol or the dextran.
5. as any described formulation method in the claim 1～4, it is characterized in that: the agent of described injection pH regulator is one or more in hydrochloric acid, sodium hydroxide, sodium bicarbonate, sodium citrate, the citric acid.
6. as any described formulation method in the claim 1～4, it is characterized in that: the dextro Borneolum Syntheticum composition is greater than 90% in the described Borneolum Syntheticum.
7. adopt as any Borneolum Syntheticum injection that described formulation method makes in the claim 1～4.
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| CN200910186560A CN101703466A (en) | 2009-11-24 | 2009-11-24 | Borneol injection and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102188369A (en) * | 2011-04-27 | 2011-09-21 | 中国人民解放军第二军医大学 | Easily sublimating medicament injection solution and intravenous injection thereof |
| CN102309470A (en) * | 2010-07-08 | 2012-01-11 | 谭友标 | Cold oil and preparation process thereof |
| CN102526112A (en) * | 2012-02-20 | 2012-07-04 | 苏州工业园区天龙制药有限公司 | Sustained-release pearl clear-sighted eye drops and preparation method thereof |
-
2009
- 2009-11-24 CN CN200910186560A patent/CN101703466A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102309470A (en) * | 2010-07-08 | 2012-01-11 | 谭友标 | Cold oil and preparation process thereof |
| CN102188369A (en) * | 2011-04-27 | 2011-09-21 | 中国人民解放军第二军医大学 | Easily sublimating medicament injection solution and intravenous injection thereof |
| CN102526112A (en) * | 2012-02-20 | 2012-07-04 | 苏州工业园区天龙制药有限公司 | Sustained-release pearl clear-sighted eye drops and preparation method thereof |
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Application publication date: 20100512 |