CN109498547A - A kind of Local injection of Bleomycin A_5 preparation and preparation method thereof - Google Patents
A kind of Local injection of Bleomycin A_5 preparation and preparation method thereof Download PDFInfo
- Publication number
- CN109498547A CN109498547A CN201811562611.XA CN201811562611A CN109498547A CN 109498547 A CN109498547 A CN 109498547A CN 201811562611 A CN201811562611 A CN 201811562611A CN 109498547 A CN109498547 A CN 109498547A
- Authority
- CN
- China
- Prior art keywords
- bleomycin
- preparation
- local injection
- phosphatide
- glyceride
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/14—Peptides containing saccharide radicals; Derivatives thereof, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
The present invention discloses a kind of Local injection of Bleomycin A_5 preparation and preparation method thereof.The Local injection of Bleomycin A_5 preparation includes the bleomycin A5 hydrochloride of 0.05-0.1g, 2-5ml ethyl alcohol, 15-25g phosphatide, 20-30g glyceride and 2-3g stabilizer；Bleomycin A5 hydrochloride, ethyl alcohol, phosphatide, glyceride and stabilizer are uniformly mixed, Local injection of Bleomycin A_5 preparation is obtained.Local injection of Bleomycin A_5 preparation of the invention is serious, located subcutaneously deeper hemangioma for treating by lesion, has the effect of long-acting slow-release, and compatibility is good in vivo, is easy to be metabolized.
Description
Technical field
The invention belongs to drug fields, and in particular to a kind of Local injection of Bleomycin A_5 preparation and preparation method thereof.
Background technique
Hemangioma (hemangioma) is formed be common in skin and soft group by angioblast hyperplasia during embryo
Interior congenital benign tumour or hemangioma are knitted, when being more common in baby due or after birth soon.Remaining embryo is thin at blood vessel
Born of the same parents, active endothelium sample plumule are invaded to adjacent tissue, form endothelium batten rope, be connected with left blood vessel through Guan Huahou and
Hemangioma is formed, blood vessel self-organizing system in tumor is not connected with peripheral vessels.Hemangioma can betide whole body everywhere, wherein mostly
Number betides facial skin, subcutaneous tissue and mucous membrane of mouth, such as tongue, lip, mouth bottom tissue, and minority betides in jawbone or deep
Tissue.
Currently, having drug therapy, operation excision, laser therapy, injection of sclerosing agent etc. to hemangioma cure common method, answer
Suitable treatment means are selected according to factors such as the type of lesion, position, the depth and the ages of patient.At present to it is located subcutaneously compared with
The hemangioma infant of deep position being in a bad way other treatment means effects in addition to operative treatment are all undesirable.If operative treatment
Since lesion locations rich blood vessel, blood volume are big, surgical procedure risk is larger, is not suitable for infant.Laser therapy is to shallow
Hemangioma cure effect is obvious, and side effect is smaller, but can not treat deep-level blood vessel tumor.Injection of sclerosing agent can make vascular tissue
Fibrosis, locking generate cicatricial contraction, reduce knurl, but after injection of sclerosing agent, lesion locations vascular tissue fibrosis, in turn
The local function of body is influenced, and is not suitable for the hemangioma for the treatment of key position and large volume.
Drug therapy hemangioma is a kind of important means, and treating angiomatous drug has Propranolol, timolol, puts down
Positive mycin etc..Bleomycin A5 (Pingyangmycin) is isolated anti-tumor from the unwrapping wire bacteria culture fluid in soil
Raw element, it is close with external bleomycin ingredient through studying, the synthesis and cutting DNA chain of cancer cell DNA can be inhibited, it is thin to influence cancer
Born of the same parents' metabolic function promotes tumor cell degeneration, necrosis.Bleomycin A5 is mainly used for treating G. cephalantha, malignant lymphoma, mammary gland
Cancer, the cancer of the esophagus and nasopharyngeal carcinoma etc. also can be used for the squamous carcinoma of its elsewhere such as lung, cervix and skin.Application No. is
200710051885.8 Chinese patent disclose it is a kind of treat angiomatous injection, by bleomycin A5, interferon, fill in rice
Pine, adrenaline, lidocaine and water for injection are made.But its half-life short, short-term large dosage use the drug, it may
The toxicity of whole body is caused, wherein pulmonary fibrosis is one of side effect the most serious.
When using class of medications, different dosage forms can be selected according to different lesion situations.Such as skin surface
Hemangioma, can be using external preparations such as cream preparation or patches；Internal lesser hemangioma, can use oral preparation；And
Serious for lesion, located subcutaneously deeper hemangioma, external preparation are difficult to achieve the effect that treatment, take orally because of topical remedy
Concentration not high be also extremely difficult to therapeutic effect.Drug injection is a kind of common pharmaceutical dosage form, effect rapidly it is reliable, not by
PH, enzyme, food etc. influence, no first pass effect, can play whole body or local positioning effect.But normal injection agent is easy to be diffused into
Whole body, can not be to diseased region long-acting treatment.
Therefore, clinic needs a kind of Local injection of Bleomycin A_5 durative action preparation, provides that a kind of lesion is serious, position for treating
It, can be with sustained release drugs after diseased region injection in the locally injecting preparation of subcutaneously deeper vascular malformation.
Summary of the invention
In response to the problems existing in the prior art, the purpose of the present invention is to provide a kind of Local injection of Bleomycin A_5 preparations, use
In treatment lesion, serious, located subcutaneously deeper hemangioma, has the effect of long-acting slow-release, and compatibility is good in vivo, holds
Easily metabolism.
To achieve the above object, the technical solution adopted by the present invention is that:
A kind of Local injection of Bleomycin A_5 preparation, bleomycin A5 hydrochloride, 2-5ml ethyl alcohol including 0.05-0.1g, 15-25g
Phosphatide, 20-30g glyceride and 2-3g stabilizer.
Further, the phosphatide includes one or both of soybean lecithin and egg yolk lecithin, preferably soybean ovum
Phosphatide.
Further, the glyceride includes one in glyceryl dioleate, olein and tristerin
Kind is a variety of, preferably glyceryl dioleate.
Further, the stabilizer is poloxamer188 or low-molecular-weight polyethylene glycol.
The present invention also provides the preparation methods of the Local injection of Bleomycin A_5 preparation: by bleomycin A5 hydrochloride, phosphatide,
Glycerolipid and stabilizer, which are uniformly mixed, obtains working fluid, finally through filtration sterilization, obtains Local injection of Bleomycin A_5 preparation.
Compared with prior art, the beneficial effects of the present invention are:
(1) carrier of the lyotropic liquid crystal material as the ejection preparation of bleomycin A5 is used, compared to common liquid injection
Preparation can discharge for a long time drug in lesion locations, and the peak valley effect drop of drug is reduced while improving diseased region curative effect
The toxic side effect of low whole body, can be used for treating that lesion is serious, located subcutaneously deeper hemangioma.
(2) select phosphatide and glyceride as lyotropic liquid crystal material, easy metabolism good with human compatibility is manufactured flat
The viscosity of positive mycin locally injecting preparation is small, convenient for injection；Chance water is transformed into liquid crystal after being injected into lesion locations, plays good
Slow releasing function, slow-release time are more than 20 days.
(3) stabilizer is added in the formulation, is conducive to the stability for improving solute liquid crystal, extends slow-release time.
Detailed description of the invention
Fig. 1 is that Local injection of Bleomycin A_5 agent in vitro is sustained accumulative release rate curve；
Fig. 2 is Local injection of Bleomycin A_5 preparation rabbit plasma concentration curve.
Specific embodiment
Below in conjunction with the embodiment of the present invention, technical solution of the present invention is clearly and completely described, it is clear that
Described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.Based on the implementation in the present invention
Example, those of ordinary skill in the art's all other embodiment obtained under the conditions of not making creative work belong to
The scope of protection of the invention.
Embodiment 1
A kind of Local injection of Bleomycin A_5 preparation, including 0.05g bleomycin A5 hydrochloride, 2ml dehydrated alcohol, 15g soybean ovum
Phosphatide, 20g glyceryl dioleate and 2g poloxamer188.The preparation method is as follows: by 0.05g bleomycin A5 hydrochloride first with 2ml
Dehydrated alcohol mixing, formed suspension, then again with 15g soybean lecithin, 20g glyceryl dioleate and 2g poloxamer188
Mixing, persistently stirs 2h, finally through filtration sterilization, obtains Local injection of Bleomycin A_5 preparation A1.
Embodiment 2
A kind of Local injection of Bleomycin A_5 preparation, including 0.08g bleomycin A5 hydrochloride, 4ml dehydrated alcohol, 20g soybean ovum
Phosphatide, 25g glyceryl dioleate and 2g polyethylene glycol 200.The preparation method is as follows: by 0.08g bleomycin A5 hydrochloride first with 4ml
Dehydrated alcohol mixing, formed suspension, then again with 20g soybean lecithin, 25g glyceryl dioleate and 2g polyethylene glycol 200
Mixing, persistently stirs 3h, finally through filtration sterilization, obtains Local injection of Bleomycin A_5 preparation A2.
Embodiment 3
A kind of Local injection of Bleomycin A_5 preparation, including 0.06g bleomycin A5 hydrochloride, 3ml dehydrated alcohol, 20g yolk ovum
Phosphatide, 30g olein and 3g poloxamer188.The preparation method is as follows: by 0.06g bleomycin A5 hydrochloride, 20g yolk
Lecithin, 30g olein and the mixing of 3g poloxamer188, persistently stir 4h, finally through filtration sterilization, obtain Pingyang
Mycin locally injecting preparation A3.
Embodiment 4
A kind of Local injection of Bleomycin A_5 preparation, including 0.1g bleomycin A5 hydrochloride, 5ml dehydrated alcohol, 25g yolk lecithin
Rouge, 20g tristerin and 2g polyethylene glycol 400.The preparation method is as follows: by 0.1g bleomycin A5 hydrochloride first with 5ml without
Water-ethanol mixing, forms suspension, then mixed with 25g egg yolk lecithin, 20g tristerin and 2g polyethylene glycol 400 again
It closes, persistently stirs 2h, finally through filtration sterilization, obtain Local injection of Bleomycin A_5 preparation A4.
Reference examples 1
A kind of Local injection of Bleomycin A_5 preparation, including it is big including 0.08g bleomycin A5 hydrochloride, 4ml dehydrated alcohol, 20g
Beans lecithin and 25g glyceryl dioleate.The preparation method is as follows: 0.08g bleomycin A5 hydrochloride is mixed with 4ml dehydrated alcohol first
It closes, forms suspension, then persistently stir 3h with 20g soybean lecithin and 25g glyceryl dioleate again, finally by filtering out
Bacterium obtains Local injection of Bleomycin A_5 preparation B1.
Reference examples 2
A kind of Local injection of Bleomycin A_5 preparation, including 0.08g bleomycin A5 hydrochloride, 4ml dehydrated alcohol, 25g yolk ovum
Phosphatide, 15g olein and 2g polyethylene glycol 200.The preparation method is as follows: by 0.08g bleomycin A5 hydrochloride first with 4ml
Dehydrated alcohol mixing, formed suspension, then again with 25g egg yolk lecithin, 15g olein and 2g polyethylene glycol 200,
4h is persistently stirred, finally through filtration sterilization, obtains Local injection of Bleomycin A_5 preparation B2.
Reference examples 3
A kind of Local injection of Bleomycin A_5 preparation, including 0.08g bleomycin A5 hydrochloride, 4ml dehydrated alcohol, 10g yolk ovum
Phosphatide, 30g olein and 2g polyethylene glycol 200.The preparation method is as follows: by 0.08g bleomycin A5 hydrochloride first with 4ml
Dehydrated alcohol mixing, formed suspension, then again with 10g egg yolk lecithin, 30g olein and 2g polyethylene glycol 200,
4h is persistently stirred, finally through filtration sterilization, obtains Local injection of Bleomycin A_5 preparation B3.
Application examples
Local injection of Bleomycin A_5 preparation anti-washout capacity and syringeability experiment:
Take respectively the Local injection of Bleomycin A_5 preparation A1-A4 prepared in 0.5ml embodiment 1-4 and comparative example 1-3,
B1-B3 is placed in 5ml centrifuge tube, and 4ml water is added, and has seen whether that diffusion phenomena, no diffusion phenomena illustrate that preparation resists dilute dissipate
It is functional.Diffusion is denoted as "-", does not spread and is denoted as "+".It takes Local injection of Bleomycin A_5 preparation A1-A4, B1-B3 respectively again, adopts
Syringeability experiment is carried out with 1ml sterilizing syringe and No. 5 syringe needles, preparation, which can be injected smoothly, shows that its syringeability is good.It is smoothly logical
Overwriting is "+", cannot pass through and be denoted as "-".Test result is as shown in table 1.
Table 1: anti-washout capacity and syringeability experiment
| Sample number | Anti-washout capacity | Syringeability |
| A1 | + | + |
| A2 | + | + |
| A3 | + | + |
| A4 | + | + |
| B1 | - | + |
| B2 | + | - |
| B3 | - | + |
The sustained release experiment of Local injection of Bleomycin A_5 agent in vitro:
Local injection of Bleomycin A_5 preparation A1-A4, B1-B3 of Example 1-4, reference examples 1-3, using Bag filter method into
The experiment of row extracorporeal releasing characteristic is investigated.Dissolution medium is water.Specific experiment step are as follows: take 1g Local injection of Bleomycin A_5 system respectively
The water of equivalent is added in agent, stands 0.5h and forms liquid crystal.Then it is added in bag filter, both ends are clamped with clip, and bag filter is put into
In the water of 300ml, it is T=37 DEG C that water-bath, which keeps temperature, and revolving speed 30r/min seals whole system, prevents from evaporating, respectively
In the 0.5th, 1,2,3,4,5,6,7,8,9,10,11,12 day sampling 1mL, 1mL water is filled into again every time.The sample of taking-up crosses 0.22 μm
Miillpore filter, HPLC measure Pinyangmycin concentration.The accumulative release rate Q at each time point is calculated, as shown in Figure 1.
From figure 1 it appears that either embodiment 1-4 has the technical effect being well sustained, and more than 10 days
Can just be sustained terminates, thus proves the technical effect that locally injecting preparation made of bleomycin A5 hydrochloride is had long-acting slow-release.
And stabilizer is not used in B1, anti-washout capacity is poor, and bleomycin A5 hydrochloride is water solubility, and the locally injecting preparation of formation is in water
Rate of release it is too fast, the general 3 days time reaches maximum release rate.The proportion of B2 and B3 glyceride and phosphatide falls in guarantor
It protects except range, although there is the presence of stabilizer, the liquid crystal stability formed is poor, causes rate of release also very fast, B2 sample
4 days release rates of product are higher than 90%, but the last release rate of B3 sample is only above 80%, and possible reason is B3 phosphatide
Content is higher, and bleomycin A5 hydrochloride is water soluble drug, poor with the intersolubility of phosphatide, and it is stagnant to will lead to part bleomycin A5 hydrochloride
It stays.But in vivo, it can be realized the complete release of bleomycin A5 hydrochloride since phosphatide can be degraded by human body.
The experiment of Local injection of Bleomycin A_5 preparation animal plasma:
The same batch sample of Example 2 carries out animal plasma experiment.Choose 1 adult healthy rabbit, weight
About 2kg.Sample 1ml is subcutaneously injected to rabbit, then respectively the 1st, 2,3,4,5,6,7,8,9,10,12,14,16,18,20
It takes blood 1ml to rabbit.The method recorded using " two middle bleomycin A5 hydrochlorides of " Chinese Pharmacopoeia " version in 2015 ", by efficient
The blood concentration of liquid chromatography for measuring bleomycin A5.Experimental result is as shown in Fig. 2, minimal detectable concentration 10ng/mL.
From figure 2 it can be seen that bleomycin A5 reached peak concentration of drug at the 5th day in the intracorporal sustained release of rabbit, about
120ng/mL；The 4-7 days blood concentrations keep relatively stable, are 100ng/mL or so.The 1-3 days blood concentrations are continuously and healthily
Increase, mainly the slow release effect due to Local injection of Bleomycin A_5 preparation；And the 8th day blood concentration is greatly reduced, mainly
Since the result with the internal consumption superposition of drug is greatly reduced in slow release speed.In addition, it is found that the compared with sustained release result in vitro
Being greatly reduced for blood concentration may be to lead since environment is destroyed Local injection of Bleomycin A_5 preparation structure in vivo within 8-9 days
Causing locally injecting preparation at the about the 7th day, almost sustained release is complete.Blood concentration persistently reduces within the 10-12 days, and be in compared with
Low concentration, terminating below detectable concentration.Dawn will also realize that by blood medicine curve, if injection application again, rabbit at the 8th or the 9th day
Blood concentration can smoothly reach certain concentration, reach preferable therapeutic effect.
It although an embodiment of the present invention has been shown and described, for the ordinary skill in the art, can be with
A variety of variations, modification, replacement can be carried out to these embodiments without departing from the principles and spirit of the present invention by understanding
And modification, the scope of the present invention is defined by the appended.
Claims (8)
1. a kind of Local injection of Bleomycin A_5 preparation, which is characterized in that bleomycin A5 hydrochloride, 2-5ml second including 0.05-0.1g
Alcohol, 15-25g phosphatide, 20-30g glyceride and 2-3g stabilizer.
2. a kind of Local injection of Bleomycin A_5 preparation according to claim 1, which is characterized in that the phosphatide includes soybean
One or both of lecithin and egg yolk lecithin.
3. a kind of Local injection of Bleomycin A_5 preparation according to claim 1, which is characterized in that the phosphatide is yolk ovum
Phosphatide.
4. a kind of Local injection of Bleomycin A_5 preparation according to claim 1, which is characterized in that the ethyl alcohol is anhydrous second
Alcohol.
5. a kind of Local injection of Bleomycin A_5 preparation according to claim 1, which is characterized in that the glyceride packet
Include one of glyceryl dioleate, olein and tristerin or a variety of.
6. a kind of Local injection of Bleomycin A_5 preparation according to claim 1, which is characterized in that the glyceride is two oil
Acid glyceride.
7. a kind of Local injection of Bleomycin A_5 preparation according to claim 1, which is characterized in that the stabilizer is pool Lip river
Husky nurse 407 or low-molecular-weight polyethylene glycol.
8. the preparation method of any one of the claim 1-7 Local injection of Bleomycin A_5 preparation, which is characterized in that put down hydrochloric acid
Positive mycin, ethyl alcohol, phosphatide, glycerolipid and stabilizer are uniformly mixed, and are obtained working fluid, finally through filtration sterilization, are obtained Pingyang
Mycin locally injecting preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811562611.XA CN109498547B (en) | 2018-12-20 | 2018-12-20 | Pingyangmycin local injection preparation and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811562611.XA CN109498547B (en) | 2018-12-20 | 2018-12-20 | Pingyangmycin local injection preparation and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109498547A true CN109498547A (en) | 2019-03-22 |
| CN109498547B CN109498547B (en) | 2022-04-12 |
Family
ID=65753834
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811562611.XA Active CN109498547B (en) | 2018-12-20 | 2018-12-20 | Pingyangmycin local injection preparation and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109498547B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109431997A (en) * | 2018-12-20 | 2019-03-08 | 武汉科福新药有限责任公司 | A kind of rapamycin locally injecting preparation and preparation method thereof |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080299220A1 (en) * | 2003-08-04 | 2008-12-04 | Dov Tamarkin | Hydrophilic, non-aqueous pharmaceutical carriers and compositions and uses |
| CN102836418A (en) * | 2012-09-18 | 2012-12-26 | 武汉大学 | Pingyangmycin polyethylene glycol (PEG)-polycaprolactone (PCL)-polyethylene glycol (PEG) temperature-sensitive slow-release gel, as well as preparation method and application of same |
| CN103040764A (en) * | 2012-12-18 | 2013-04-17 | 海南百思特医药科技有限公司 | Bleomycin hydrocloride lipidosome injection |
| CN105726484A (en) * | 2016-02-25 | 2016-07-06 | 天津中医药大学 | Tetrandrine liquid crystal nanoparticle preparation for eyes and preparation method thereof |
| CN107233312A (en) * | 2016-12-31 | 2017-10-10 | 广东药科大学 | A kind of Etoposide cubic liquid crystal and its preparation method and application |
| CN108309931A (en) * | 2018-05-08 | 2018-07-24 | 武汉百纳礼康生物制药有限公司 | A kind of preparation and preparation method thereof for treating synovitis |
| CN108379269A (en) * | 2018-04-20 | 2018-08-10 | 武汉百纳礼康生物制药有限公司 | A kind of sustained release preparation and preparation method thereof for Postoperative Analgesia After |
| US20180311163A1 (en) * | 2004-06-04 | 2018-11-01 | Camurus Ab | Lipid depot formulations |
-
2018
- 2018-12-20 CN CN201811562611.XA patent/CN109498547B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080299220A1 (en) * | 2003-08-04 | 2008-12-04 | Dov Tamarkin | Hydrophilic, non-aqueous pharmaceutical carriers and compositions and uses |
| US20180311163A1 (en) * | 2004-06-04 | 2018-11-01 | Camurus Ab | Lipid depot formulations |
| CN102836418A (en) * | 2012-09-18 | 2012-12-26 | 武汉大学 | Pingyangmycin polyethylene glycol (PEG)-polycaprolactone (PCL)-polyethylene glycol (PEG) temperature-sensitive slow-release gel, as well as preparation method and application of same |
| CN103040764A (en) * | 2012-12-18 | 2013-04-17 | 海南百思特医药科技有限公司 | Bleomycin hydrocloride lipidosome injection |
| CN105726484A (en) * | 2016-02-25 | 2016-07-06 | 天津中医药大学 | Tetrandrine liquid crystal nanoparticle preparation for eyes and preparation method thereof |
| CN107233312A (en) * | 2016-12-31 | 2017-10-10 | 广东药科大学 | A kind of Etoposide cubic liquid crystal and its preparation method and application |
| CN108379269A (en) * | 2018-04-20 | 2018-08-10 | 武汉百纳礼康生物制药有限公司 | A kind of sustained release preparation and preparation method thereof for Postoperative Analgesia After |
| CN108309931A (en) * | 2018-05-08 | 2018-07-24 | 武汉百纳礼康生物制药有限公司 | A kind of preparation and preparation method thereof for treating synovitis |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109431997A (en) * | 2018-12-20 | 2019-03-08 | 武汉科福新药有限责任公司 | A kind of rapamycin locally injecting preparation and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109498547B (en) | 2022-04-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2270003C2 (en) | Paclitaxel-base medicinal agent stabilized with albumin for treatment of solid tumor | |
| EP2952184B1 (en) | Pharmaceutical formulation for treating pancreatic cancer | |
| WO2016127847A1 (en) | Application of chlorogenic acid in preparing medicines for treating melanoma and medicines for treating melanoma | |
| CN111346081B (en) | New use of pharmaceutical composition comprising n-pentanoic acid, indolpropanic acid and sodium n-butyrate | |
| CN105983097B (en) | Anti-tumor preparation and preparation method thereof | |
| CN109498547A (en) | A kind of Local injection of Bleomycin A_5 preparation and preparation method thereof | |
| CN106389329B (en) | A kind of Dipyridamole Orally taken emulsion drug delivery system and preparation method thereof | |
| Yu et al. | Antitumor effect of intratumoral administration of fluorouracil/epinephrine injectable gel in C3H mice | |
| EA007685B1 (en) | Pharmaceutical composition containing toluene sulfonamide and method of use thereof | |
| CN103191119A (en) | Use of itraconazole in inhibiting of Akt kinase (protein kinase B) activity | |
| CN110870918A (en) | Pharmaceutical composition containing amino acid nutrients and antitumor chemotherapeutic drugs and application thereof | |
| CN100563644C (en) | A kind of carmustine sustained-release implantation agent for the treatment of entity tumor | |
| CN104042645B (en) | Compound amino acid injection | |
| CN102526714B (en) | Medicine composition for curing tumour and preparation method thereof | |
| CN101185629A (en) | Decitabine sustained-release preparation for treating solid tumor | |
| CN100563645C (en) | A kind of Beisalutin sustained-release implantation agent for the treatment of entity tumor | |
| CN101181232B (en) | Marseilledinun sustained-release implantation agent for curing entity tumour | |
| JP3429327B2 (en) | Amino acid infusion for cancer | |
| CN101219101A (en) | Fludarabine sustained-release implantation agent for treating solid tumors | |
| CN101224185A (en) | Bosutinib sustained release implant for treating solid tumors | |
| JPH02306914A (en) | Amino acid pharmaceutical for cancer | |
| CN109431997B (en) | Local rapamycin injection and preparation method thereof | |
| CN102716465B (en) | Pharmaceutical composite for treating tumor and preparation method of pharmaceutical composite | |
| CN101204369A (en) | Sorafenib sustained-release implant treating for solid tumor | |
| CN102698252B (en) | Medicine composition for treating tumor and preparation method for medicine composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |