CN105727260A - Long-acting preparation of follicle-stimulating hormone - Google Patents
Long-acting preparation of follicle-stimulating hormone Download PDFInfo
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- CN105727260A CN105727260A CN201610075671.3A CN201610075671A CN105727260A CN 105727260 A CN105727260 A CN 105727260A CN 201610075671 A CN201610075671 A CN 201610075671A CN 105727260 A CN105727260 A CN 105727260A
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- stimulating hormone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/24—Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- 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
-
- 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
- A61K9/08—Solutions
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
Abstract
The invention provides a long-acting preparation of follicle-stimulating hormone.The preparation is prepared from follicle-stimulating hormone, a sodium citrate-citrate buffer solution, heparin and hyaluronic acid.The follicle-stimulating hormone is hypophysis follicle-stimulating hormone or genetic recombination follicle-stimulating hormone.The preparation is injection or a freeze-dried powder needle.In the preparation, the ratio of heparin to hyaluronic acid is 2:1 to 1:5.When the preparation is injection, 100-1000 IU of follicle-stimulating hormone, 10-50 mg of sodium citrate, 0.1-1.0 mg of citric acid, 1-10 mg of heparin and 5-50 mg of hyaluronic acid are added to every 1 ml of normal saline or water for injection.The preparation can be applied to superovulation and estrus induction of the animal husbandry.
Description
[technical field]
The present invention relates to the durative action preparation of a kind of follicule-stimulating hormone (FSH), belong to materia medica, molecular medicine and disease
Prevention and control field.
[background technology]
Follicule-stimulating hormone (FSH) (Follicle-stimulating hormone, FSH) be a kind of by animal brain hypophysis before
The glycoprotein promoting sexual gland hormone of leaf secretion.There is the effects such as the regulation growth of body, sexual maturity and breeding.
FSH can promote endometrial growth jenny, ovulate, stimulates many follicular developments etc..Target
The specific receptor of FSH is there is on cell, after FSH follicle-stimulating hormone receptor on cell membrane is combined,
By G-protein coupling mechanism activated adenyl cyclase, make intracellular cAMP increase or cause calcium from
Stream in son, thus the metabolism or functional activity on cell produces impact.FSH produces two after being combined with receptor
Plant effect.On the one hand activation aromatase, on the other hand induction LH receptor is formed.Endo cell is at LH
Effect under to provide 19 carbon substrates-androstenedione or these substrates of testosterone to enter granule by basement membrane thin
Born of the same parents, the aromatase of activation is changed into 17-β estradiol (E2) them, and theca interna itself can only
Produce minimal amount of estrogen.Estrogen is worked in coordination with FSH and is made granular cell hypertrophy, and endo cell breaks up, ovum
Bubble liquid forms follicular antrum and expands, so that ovarian follicular growth and growth.
Breeding is the key factor affecting animal husbandry overall efficiency.How to improve animal reproduction rate always
It it is all an emphasis of herding field tackling key problem.In modern agriculture, the artificial insemination of breeding stock is the most general
Time, particularly milch cow (the 75% of all fertilization types) and pig (the 85% of all fertilization types)
On application.Embryo transfer technology is the most great revolution in livestock reproduction field, and it can improve excellent
The breeding potential of elegant breeding stock, makes full use of high-quality gene, to breeding, the conservation of domestic animal, introduces a fine variety and warp
The raising of Ji benefit all has very important significance.But, carry out domestic animal expanding propagation by various means
Precondition is in good time oestrusing and a large amount of high-quality ovums source of animal.The animal appropriate to breeding stock injection swashs
Element then can meet these preconditions: the most general like product has Ovagen (follicle
Stimulin comes from sheep pituitary extract, and New Zealand produces) and Folltropin-V (follicule-stimulating hormone (FSH) comes from pig
Pituitary extract, Canada produces), can be used for superovulation (i.e. increases mature follicle number, arranges every time
Ovum number is up to more than 10) and coordinate the estrus synchronization (key before artificial insemination, embryo transfer
Technology).In order to reach superovulation, Ovagen and Folltropin-V is both needed to inject eight times.
The domestic injection in recent years produced by Ningbo of Zhejiang the second hormone factory's production and Hangzhou animal drug factory is hung down
Body follicule-stimulating hormone (FSH), injects 2-5 time per course for the treatment of, can promote ovarian follicular growth grow and estrogen point
Secrete, cause animal normally to oestrus, but the most do not recommend for superovulation.Current various like products,
Being both needed to multiple injection, not only cost of labor is high, more because repeatedly alarming animal and impact effect.For many years,
The long-acting follicule-stimulating hormone (FSH) of numerous and confused research in industry, including gene recombinaton, durative action preparation, change route of administration
Deng distinct methods, it is intended to reduce frequency injection.Once had been reported that with polyvinylpyrrolidone (J Reprod Dev,
59 (2): 214-218,2013), after dissolving Folltropin-V, Thailand cattle only injects super several rows once
Ovum effect, with intramuscular injection every day 2 times, effect for three days on end is identical.Folltropin-V is dissolved
In the hyaluronic acid solution of 20mg/ml, injection 8 continuously in milk beef injection effect once, with 4 days
Secondary effect identical (Anim Reprod Sci, 129:7-13,2011).Due to hyaluronic acid concentration
Excessive, it is difficult to during injection be completely exhausted out medicinal liquid, animal curative effect individual variation is bigger.Hyaluronic acid is molten
After liquid concentration is reduced to 5mg/ml, improves administration easness, but must every other day be administered, i.e. 2
Secondary administration, its effect just with 4 days in continuously injection 8 times identical.
[summary of the invention]
The technical problem to be solved in the present invention, is to provide the durative action preparation of a kind of follicule-stimulating hormone (FSH), can answer
Superovulation and estrus induction for animal husbandry.
The present invention is achieved in that
The durative action preparation of a kind of follicule-stimulating hormone (FSH), the component of described preparation is as follows: follicule-stimulating hormone (FSH), citron
Acid sodium-citrate buffer, heparin and hyaluronic acid.
Further, described follicule-stimulating hormone (FSH) is hypophysis follicule-stimulating hormone (FSH), or gene recombinaton follicle stimulates
Element.
Further, described preparation formulation is injection or freeze-dried powder.
Further, in described preparation, the ratio of heparin and hyaluronic acid is 2:1 to 1:5.
Further, when described preparation is injection, each constituent content of preparation is as follows: every 1ml physiology
Saline or water for injection add follicle stimulating hormone 100～1000IU, sodium citrate 10～50mg, citric acid
0.1～1.0mg, heparin 1～10mg, hyaluronic acid 5～50mg.
Further, described hyaluronic acid is 2～8mg.
Further, the final concentration of 4mg/ml of described heparin, the final concentration of 5mg/ml of hyaluronic acid.
Further, in the injection prescription of freeze-drying powder of described preparation, each constituent content is as follows: every 1ml physiology salt
Water or water for injection add follicle stimulating hormone 100～1000IU, sodium citrate 10～50mg, citric acid
0.1～1.0mg, mannitol 50～500mg, heparin 4～40mg, hyaluronic acid 5～50mg.
Further, described hyaluronic acid is 2～8mg.
Present invention have the advantage that
The follicule-stimulating hormone (FSH) durative action preparation that the present invention screens and optimizes, containing having slow-releasing and controlled-releasing action in prescription
Heparin and hyaluronic acid, by adjusting heparin and hyaluronic acid ratio, can be with regulating drug rate of release.
Medicine of the present invention can be applicable to superovulation and the estrus induction of animal husbandry.
[accompanying drawing explanation]
The present invention is further illustrated the most in conjunction with the embodiments.
Fig. 1 is the In Vitro Dissolution experiment of embodiment of the present invention hypophysis follicule-stimulating hormone (FSH) long-acting injection A1-3
Result curve figure.
Fig. 2 is the In Vitro Dissolution experiment of embodiment of the present invention hypophysis follicule-stimulating hormone (FSH) long-acting injection B1-3
Result curve figure.
Fig. 3 is the In Vitro Dissolution experiment of embodiment of the present invention hypophysis follicule-stimulating hormone (FSH) long-acting injection D1-3
Result curve figure.
[detailed description of the invention]
Refer to, shown in Fig. 1～3, embodiments of the invention are described in detail.
The durative action preparation of a kind of follicule-stimulating hormone (FSH) involved in the present invention, the component of described preparation is as follows: ovum
Bubble stimulin, sodium citrate-citrate buffer, heparin and hyaluronic acid；Described follicule-stimulating hormone (FSH)
For hypophysis follicule-stimulating hormone (FSH), or recombinant staphylokinase；Described preparation formulation is injection or lyophilizing
Powder pin；In described preparation, heparin is 2:1 to 1:5 with the ratio of hyaluronic acid.
When described preparation is injection, each constituent content of preparation is as follows: every 1ml normal saline or injection
With water adds follicle stimulating hormone 100～1000IU, sodium citrate 10～50mg, citric acid 0.1～1.0mg,
Heparin 1～10mg, hyaluronic acid 5～50mg.Preferably, described hyaluronic acid is 2～8mg.More excellent
, the final concentration of 4mg/ml of described heparin, the final concentration of 5mg/ml of hyaluronic acid.
In the injection prescription of freeze-drying powder of described preparation, each constituent content is as follows: every 1ml normal saline or injection
Addition follicle stimulating hormone 100～1000IU in water, sodium citrate 10～50mg, citric acid 0.1～1.0mg,
Mannitol 50～500mg, heparin 4～40mg, hyaluronic acid 5～50mg.Preferably, described transparent
Matter acid is 2～8mg.
Embodiment 1
The preparation of recombinant staphylokinase
The Chinese hamster ovary celI of stable high expressed FSH is accessed shaking flask, progressively expands, to density 1 × 106
/ ml, is designated as cultivating the 1st day.After continuous 14 days, take cell culture fluid, for purified expression product.
By Chinese hamster ovary celI medium centrifugal, rotating speed 9000g, 4 DEG C of low-temperature centrifugation 20min, collect and cultivate
Supernatant.Using molecular cut off is 10kDa membrane ultrafiltration, collects and liquid is concentrated by ultrafiltration.With Protein A parent
And chromatographic column, to concentrated solution purification, obtaining high-purity FSH albumen, purity about 98%, specific activity is
12000IU/mg.2-8 DEG C stores for future use.
Embodiment 2
The preparation of hypophysis follicule-stimulating hormone (FSH) long-acting injection
Take hypophysis follicule-stimulating hormone (FSH) (purchased from Ningbo the second hormone factory) 100000IU, be dissolved in 200ml Chinese holly
In rafter acid sodium-citrate buffer (pH6.8-7.2).Every 1 milliliter of sodium citrate-citrate buffer
(pH6.8-7.2) 30mg Han sodium citrate, citric acid 0.6mg.Taking concentration is the low of 20mg/ml
Molecular heparin (molecular weight 5000) solution (50 or 200 or 500ml), with above-mentioned hypophysis follicle
Stimulin solution mixes.Take the hyaluronic acid solution 250ml that concentration is 20mg/ml again, hang down with above-mentioned
Body follicule-stimulating hormone (FSH) mixes with the solution of Low molecular heparin.Supplement sodium citrate-citrate buffer extremely
1000ml.All process for preparation need to be carried out in hundred grades of aseptic areas.All solution are all after aseptic filtration
Use.Under agitation, by obtained solution subpackage to cillin bottle, every bottle of 10ml, obtain hypophysis
Follicule-stimulating hormone (FSH) long-acting injection.
According to the volume of added Low molecular heparin Yu hyaluronic acid, by the obtained named hypophysis of preparation
Follicule-stimulating hormone (FSH) long-acting injection A1, A2 and A3.2-8 DEG C stores for future use.Table 1 institute specific as follows
Show:
The preparation of table 1 hypophysis follicule-stimulating hormone (FSH) long-acting injection A1-3
Embodiment 3
In Vitro Dissolution is tested
The preparation A1-3 that Example 2 obtains, puts in 10ml centrifuge tube respectively, puts 37 DEG C of constant temperature trainings
Place in supporting case, in the 6th, 12,24,36,48,72,96 hour centrifugal (3000rpm),
Taking supernatant 200 microlitre, ELISA method measures FSH concentration.After each sampling, mend in centrifuge tube
Fill 200 microlitre sodium citrate-citrate buffer (pH6.8-7.2).According to measurement result, obtain molten
Go out curve, as shown in Figure 1.As seen from Figure 1 along with the increase of heparin consumption, dissolution rate substantially slows down.
After heparin final concentration is more than 4mg/ml, dissolution rate is substantially close to zero order release rate.Illustrate permissible
By adjusting Low molecular heparin consumption, regulate dissolution rate.
Embodiment 4
The preparation of rFSH long-acting injection
Take rFSH 1,000,000 IU, be dissolved in 200ml sodium citrate-citrate buffer
(pH6.8-7.2) in.Every 1 milliliter of sodium citrate-citrate buffer (pH6.8-7.2) contains citric acid
Sodium 30mg, citric acid 0.6mg.Take the Low molecular heparin (molecular weight 5000) that concentration is 10mg/ml
Solution 400ml, mixes with above-mentioned hypophysis follicule-stimulating hormone (FSH) solution.Taking concentration again is the saturating of 20mg/ml
Bright matter acid solution 250ml, mixes with the solution of Low molecular heparin with above-mentioned hypophysis follicule-stimulating hormone (FSH).Supplement
Sodium citrate-citrate buffer to 1000,4000,10000ml.All process for preparation need to be at hundred grades
Carry out in aseptic area.All solution all use after aseptic filtration.Under agitation, by obtained solution
Subpackage in cillin bottle, every bottle of 1ml, obtain rFSH long-acting injection.
According to the volume of final solution, by obtained preparation named rFSH long-acting injection
Agent B1-3.2-8 DEG C stores for future use.Concrete as shown in table 2:
The preparation of table 2 rFSH long-acting injection
Carrying out In Vitro Dissolution experiment according to embodiment 3 method, result is shown in Fig. 2.As shown in Figure 2, liver is worked as
After element concentration is fixing with hyaluronic acid consumption, each prescription dissolution rate is basically identical.Illustrate that stripping curve takes
Certainly in heparin and hyaluronic acid consumption, and unrelated with FSH kind and final concentration.
Embodiment 5
The preparation of injection long-acting restructuring hypophysis follicule-stimulating hormone (FSH)
Prepare rFSH injection, according to B1-3 preparation prescription in prescription additionally
Add mannitol, in every preparation unit (i.e. every injection) containing mannitol 100,250,500mg.
According to conventional lyophilizing technique lyophilization, obtain freeze-dried powder C1-3.Room temperature condition preserves.
Take freeze-dried powder C1-3, be dissolved in 10ml sodium citrate-citrate buffer.According to embodiment 3
Method carries out In Vitro Dissolution experiment.Result is similar with Fig. 2 result.Illustrate stripping curve depend on heparin with
Hyaluronic acid, and unrelated with FSH dosage form.
Embodiment 6
The impact on dissolution rate of the hyaluronic acid consumption
Take rFSH 100,000 IU, be dissolved in 200ml sodium citrate-citrate buffer
(pH6.8-7.2) in.Every 1 milliliter of sodium citrate-citrate buffer (pH6.8-7.2) contains citric acid
Sodium 30mg, citric acid 0.6mg.Take the Low molecular heparin (molecular weight 5000) that concentration is 10mg/ml
Solution 400ml, mixes with above-mentioned hypophysis follicule-stimulating hormone (FSH) solution.Taking concentration again is the saturating of 20mg/ml
Bright matter acid solution (100ml, or 200ml, or 400ml) and above-mentioned hypophysis follicule-stimulating hormone (FSH) with low point
The solution mixing of sub-heparin.Supplement sodium citrate-citrate buffer to 1000ml.All process for preparation
Need to carry out in hundred grades of aseptic areas.All solution all use after aseptic filtration.Under agitation, by gained
To solution subpackage in cillin bottle, every bottle of 1ml, obtain rFSH long-acting injection.
According to the volume of final solution, by obtained preparation named rFSH long-acting injection
Agent D1-3.2-8 DEG C stores for future use.Shown in table 3 specific as follows:
The preparation of table 3 rFSH long-acting injection
Carrying out In Vitro Dissolution experiment according to embodiment 3 method, result is as it is shown on figure 3, along with hyaluronic acid
Consumption increases, and dissolution rate is gradually increased.
Embodiment 7
Intracorporeal active experiment
With reference to the Pharmacopoeia of the People's Republic of China 2010 editions two, annex " follicule-stimulating hormone (FSH) biometric
Determine method ", measure the biologic activity of prepared FSH preparation.
(1) laboratory animal: immaturity Sprague Dawley female rats, 40 ± 2g, 19-22 day
Age, often group 8；
(2) dilute solution: human chorionic gonadotropin (hCG) in dissolving with 1mg/ml BSA solution,
It is configured to 20IU/ml hCG solution, mixes standby；
(3) standard solution: test the same day, takes 190IU/ bottle FSH standard substance 1, with above
Dilute solution is configured to high, normal, basic three concentration, is respectively as follows: 10IU/ml, 5IU/ml, 2.5IU/ml；
(4) need testing solution: test same day, with dilute solution above above-mentioned solvent by indicating titer general
Test sample is configured to high, normal, basic three concentration, is respectively as follows: 30IU/ml, 15IU/ml, 7.5IU/ml；
(5) algoscopy: in the every day roughly the same time, gives the often group corresponding medicine of rat skin lower injection respectively
Thing, standard solution or need testing solution 0.5ml.Standard solution injects three days continuously, once a day.
Test sample only in test injection in first day once, injects dilute solution in latter two days.Inject in last
After 24h, put to death rat, extract ovary, peel off adhering tissue, remove fallopian tube and weigh.According to pharmacopeia
In (annex Ⅹ IV) Bioassay-statistical method, quantitative response algoscopy calculating test sample long-acting FSH biology is lived
Property.
Institute's test formulation is A2, B2, C2, D2, and result illustrates four kinds of preparations of all tests, injection
Biological acdtivity in vivo once, consistent with the standard substance of the same dose injecting 3 times continuously.This is described
Four kinds of preparations all can play FSH slow releasing function, can use as long-acting FSH.
The follicule-stimulating hormone (FSH) durative action preparation that the present invention screens and optimizes, containing having slow-releasing and controlled-releasing action in prescription
Heparin and hyaluronic acid, by adjusting heparin and hyaluronic acid ratio, can be with regulating drug rate of release.
Medicine of the present invention can be applicable to superovulation and the estrus induction of animal husbandry.
Although the foregoing describing the detailed description of the invention of the present invention, but it is familiar with the technology people of the art
Member should be appreciated that our described specific embodiment is merely exemplary rather than for this
The restriction of bright scope, those of ordinary skill in the art are in the equivalence made according to the spirit of the present invention
Modify and change, all should contain in the scope of the claimed protection of the present invention.
Claims (9)
1. the durative action preparation of a follicule-stimulating hormone (FSH), it is characterised in that: the component of described preparation is as follows:
Follicule-stimulating hormone (FSH), sodium citrate-citrate buffer, heparin and hyaluronic acid.
The durative action preparation of a kind of follicule-stimulating hormone (FSH) the most according to claim 1, it is characterised in that: institute
Stating follicule-stimulating hormone (FSH) is hypophysis follicule-stimulating hormone (FSH), or recombinant staphylokinase.
The durative action preparation of a kind of follicule-stimulating hormone (FSH) the most according to claim 1, it is characterised in that:
Described preparation formulation is injection or freeze-dried powder.
The durative action preparation of a kind of follicule-stimulating hormone (FSH) the most according to claim 3, it is characterised in that:
In described preparation, heparin is 2:1 to 1:5 with the ratio of hyaluronic acid.
The durative action preparation of a kind of follicule-stimulating hormone (FSH) the most according to claim 4, it is characterised in that:
When described preparation is injection, each constituent content of preparation is as follows: every 1ml normal saline or water for injection
Middle addition follicle stimulating hormone 100～1000IU, sodium citrate 10～50mg, citric acid 0.1～1.0mg, liver
Element 1～10mg, hyaluronic acid 5～50mg.
The durative action preparation of a kind of follicule-stimulating hormone (FSH) the most according to claim 5, it is characterised in that:
Described hyaluronic acid is 2～8mg.
The durative action preparation of a kind of follicule-stimulating hormone (FSH) the most according to claim 6, it is characterised in that:
The final concentration of 4mg/ml of described heparin, the final concentration of 5mg/ml of hyaluronic acid.
The durative action preparation of a kind of follicule-stimulating hormone (FSH) the most according to claim 4, it is characterised in that:
In the injection prescription of freeze-drying powder of described preparation, each constituent content is as follows: in every 1ml normal saline or water for injection
Add follicle stimulating hormone 100～1000IU, sodium citrate 10～50mg, citric acid 0.1～1.0mg, manna
Alcohol 50～500mg, heparin 4～40mg, hyaluronic acid 5～50mg.
The durative action preparation of a kind of follicule-stimulating hormone (FSH) the most according to claim 8, it is characterised in that:
Described hyaluronic acid is 2～8mg.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106177912A (en) * | 2016-07-18 | 2016-12-07 | 暨南大学 | The application of CTRP3 albumen |
Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001078687A1 (en) * | 2000-04-18 | 2001-10-25 | Peptron Inc. | Injectable sustained release pharmaceutical composition and processes for preparing the same |
| WO2005051359A1 (en) * | 2003-11-19 | 2005-06-09 | The Board Of Trustees Of The University Of Illinois | Macromolecular drug complexes having improved stability and therapeutic use of the same |
| CN1879610A (en) * | 2006-04-03 | 2006-12-20 | 哈尔滨工业大学 | Method for preparing oral administered sustained-release peptide micro capsule |
| CN101361963A (en) * | 2008-09-16 | 2009-02-11 | 哈尔滨工业大学 | Preparation method of protein and peptide drugs slow-release microcapsules |
| CN101970010A (en) * | 2008-02-08 | 2011-02-09 | 拜奥吉耐里克斯股份公司 | Liquid formulation of fsh |
| CN102131483A (en) * | 2008-02-08 | 2011-07-20 | 昌达生物科技公司 | Non-polymeric compositions for controllable drug delivery |
| CN103006714A (en) * | 2013-01-06 | 2013-04-03 | 福建广生堂药业股份有限公司 | Red nocardia rubra cell wall skeleton (N-CWS) sustained release preparation and preparation method of same |
| CN103052398A (en) * | 2010-07-30 | 2013-04-17 | 辉凌公司 | Stabilization of fsh |
| CN103536960A (en) * | 2013-10-30 | 2014-01-29 | 无锡灵锡医疗器械科技有限公司 | Hydrogel capable of slowly releasing antibacterial peptide as well as preparation method thereof |
| CN104800834A (en) * | 2014-01-23 | 2015-07-29 | 中国农业科学院北京畜牧兽医研究所 | Cow superovulation sustained-release agent and preparation method thereof |
| CN104918631A (en) * | 2012-11-16 | 2015-09-16 | 法国诗华大药厂 | Single dose recombinant bovine FSH after follicular synchronisation |
-
2016
- 2016-02-03 CN CN201610075671.3A patent/CN105727260A/en active Pending
Patent Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001078687A1 (en) * | 2000-04-18 | 2001-10-25 | Peptron Inc. | Injectable sustained release pharmaceutical composition and processes for preparing the same |
| WO2005051359A1 (en) * | 2003-11-19 | 2005-06-09 | The Board Of Trustees Of The University Of Illinois | Macromolecular drug complexes having improved stability and therapeutic use of the same |
| CN1879610A (en) * | 2006-04-03 | 2006-12-20 | 哈尔滨工业大学 | Method for preparing oral administered sustained-release peptide micro capsule |
| CN101970010A (en) * | 2008-02-08 | 2011-02-09 | 拜奥吉耐里克斯股份公司 | Liquid formulation of fsh |
| CN102131483A (en) * | 2008-02-08 | 2011-07-20 | 昌达生物科技公司 | Non-polymeric compositions for controllable drug delivery |
| CN101361963A (en) * | 2008-09-16 | 2009-02-11 | 哈尔滨工业大学 | Preparation method of protein and peptide drugs slow-release microcapsules |
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