CN103006714A - Red nocardia rubra cell wall skeleton (N-CWS) sustained release preparation and preparation method of same - Google Patents
Red nocardia rubra cell wall skeleton (N-CWS) sustained release preparation and preparation method of same Download PDFInfo
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Abstract
The invention relates to a red nocardia rubra cell wall skeleton (N-CWS) sustained release preparation and a preparation method of the sustained release preparation, wherein a formula of a sustained release microcapsule is as follows: 400-1000Mug of N-CWS, 0.01-100mg of wetting agent, 0.01-100mg of emulsifier, 0.01-100mg of polycations, 0.01-100mg of polyanions and 0.01-200 mg of salt solution.
Description
Technical field
The present invention relates to field of medicaments, more specifically, relate to the Lyopgized Nocardia rubra-cell Wall Skeleton slow releasing preparation, slow-releasing microcapsule preparation particularly, the present invention also comprises the capsule that contains this slow-releasing microcapsule, tablet, granule and preparation method thereof.
Background technology
Lyopgized Nocardia rubra-cell Wall Skeleton (Nocardia rubra Cell Wall Skeleton, N-CWS) is that nocardia rubra 03-PO-8 makes after biofermentation, cell breakage, Protease Treatment and solvent extract.It belongs to biological response modifier, contains mucopeptide that several amino acids, amino sugar form and arabinose, galactose etc. among the N-CWS, is the polymer that their form.Have the body's immunity of adjusting, strengthen T cell, macrophage, NK cytoactive, have the former activity of mitogenesis, and can induce body to produce the effects such as NO.Studies have shown that by experiment it has antitumor action and to the anti-infectious function of antibacterial, viral infection.
On raw material sources, it is the breakable nocardia rubra of high yield that N-CWS produces strain, can fully satisfy the needs of N-CWS preparation large-scale production.N-CWS all has obvious inhibitory action and therapeutical effect to generation and the growth of tumour cell of animal transplanting tumor, and the carcinogen induced tumor is had obvious preventive effect, and neoplasm metastasis is also had obvious inhibitory action.The clinical trial of N-CWS shows: cancerous ascites pleural fluid and multiple solid tumor are all had good curative effect.
Lyopgized Nocardia rubra-cell Wall Skeleton (N-CWS) has the injection product listing in the market.Such as 1. Lyopgized Nocardia rubra-cell Wall Skeleton lyophilized injectable powder (trade name: born of the same parents must be good), in approval listing in 1998, be applied at anti-tumor aspect.2. Lyopgized Nocardia rubra-cell Wall Skeleton liniment (trade name: Na Kejia), be applied to anti-fungal infection, anti-human papilloma virus (anti-HPV) and treatment cervical erosion aspect, wherein state's invention number of patent application 200510077407.5 and 200510105533.7.Recent research finds that Lyopgized Nocardia rubra-cell Wall Skeleton (N-CWS) oral administration is effective to the treatment chronic atrophic gastritis, for hepatitis B virus, human nipple virus etc. remarkable inhibition is arranged all, and clinical value is high, is worth further research and development.
But the Lyopgized Nocardia rubra-cell Wall Skeleton oral absorption requires high, and the absorption that namely will aspire for stability avoids part and short-term concentration too high, requires again mouthfeel good, good stability, and existing oral formulations is difficult to reach requirement.The present invention is through research, find with suitable adjunct ingredient it to be prepared into the slow-releasing microcapsule preparation, can solve the problems of the prior art, but use the control release N-CWS of microcapsule system and have a lot of uncertainties, rate of release such as slow-releasing microcapsule, the flowability of slow-releasing microcapsule, the size of slow-releasing microcapsule and preparation technology etc.Because slow-releasing microcapsule is the fine particle that adopts filmogen that the pharmaceutically active substance enclose is become.The particle diameter of slow-releasing microcapsule behind the medicament microcapsule, generally forms flowable powder generally at micrometer range, and the difficult point of this respect mainly contains: (1) improves microcapsule preparation method, improves yield; (2) solve N-CWS stability problem in the microcapsule preparation process; (3) improve the medicine carrying capacity; (4) reduce initial burst release rate, obtain the medicine continuous release.The present invention finds a kind of solution for preparing Lyopgized Nocardia rubra-cell Wall Skeleton slow-releasing microcapsule preparation through research, make this product have appearance looks elegant, good absorbing, curative effect are high, side effect is little, good stability, discharge uniform characteristics, solve simultaneously the problems referred to above, the invention provides a kind of slow-releasing microcapsule preparation and manufacture method thereof that contains Lyopgized Nocardia rubra-cell Wall Skeleton for this reason.
Summary of the invention
The object of the invention is to N-CWS when oral, because its main component is Nocardia acid, arabinogalactan and mucopeptide, easily destroyed by the peptic digestion enzyme, provide a kind of digested enzyme of N-CWS that can prevent to destroy, make it the oral N-CWS microcapsule that steady release, bioavailability are high, can keep its effect fully.With N-CWS microcapsule and appropriate amount of auxiliary materials mixing, sieve again.Incapsulate, namely get capsule; Tabletting namely gets tablet; Make soft material, the granulate that sieves namely gets granule, and three kinds of novel forms can both thoroughly be removed the patient from the misery of injection injection.
The invention provides a kind of slow-releasing microcapsule preparation that contains Lyopgized Nocardia rubra-cell Wall Skeleton for this reason, described slow-releasing microcapsule, its prescription and preparation method are as follows:
Its preparation method is as follows:
1) first the former powder of N-CWS is prepared into N-CWS suspendible emulsion, filter removes black precipitate and emulsifying N-CWS granule completely not, obtain uniform N-CWS suspendible emulsion, lyophilized powder is made in vacuum lyophilization.
2) take N-CWS lyophilizing powder as template particles; adopting the biocompatibility macromolecule of two kinds of oppositely chargeds is the wall material; the principle that attracts each other according to the xenogenesis electric charge; these two kinds of macromolecular material one decks are combined with being close to one deck; surface at the lyophilizing powder of N-CWS forms as thin as a wafer protectiveness adventitia, obtains the N-CWS slow-releasing microcapsule.
Preferably, its preparation method is as follows:
(1) with oil medium with the N-CWS moistening, add emulsion, preparation N-CWS suspendible emulsion filters and removes black precipitate and emulsifying N-CWS granule completely not, with the uniform N-CWS suspendible of gained emulsion, makes lyophilized powder through vacuum lyophilization.
(2) place the saline solution that contains polyanion to adsorb N-CWS lyophilized powder medicine, remove the polyanion that is not adsorbed, with the saline solution washing, place the saline solution that contains polycation to adsorb the microcapsule that makes, remove the polycation that is not adsorbed, wash with saline solution; The above-mentioned adsorption step of repeating step namely obtains having assembled the high molecular N-CWS medicament microcapsule of the different numbers of plies.
Wherein, used wetting agent is selected from: purified water
Wherein emulsion is selected from: Arlacel-80, tween 80, mannitol, and their aqueous solution.If their aqueous solution, its compound method is as follows: corresponding emulsifying agent is added in an amount of purified water, and emulsifying agent accounts for 12% ~ 25% of emulsion.
Polycation is selected from, such as one or more the mixture in chitosan, protamine, poly arginine, PAH, collagen, poly-D-lysine, cation dextran, diphenylamines-4-diazo resin, substituted diphenylamine diazo resin or other the positively charged macromolecular materials.
Polyanion is selected from, such as one or more the mixture in seaweeds sodium, dextran sulfate, heparin, heparin sulfate, polyglutamic acid, sodium carboxymethyl cellulose, polyanion cellulose, kayexalate, chondroitin sulfate, hyaluronic acid or other the electronegative macromolecular materials.
Wherein, described saline solution be selected from sodium chloride, ammonium chloride, ammonium sulfate, potassium sulfate, sodium sulfate, potassium chloride,
The solution of sodium phosphate or other strong electrolytes, preferred their hydrochloric acid solution, its compound method is as follows: corresponding salt is added in an amount of purified water, and concentration of salt solution is 0.01 ~ 10M.
Preferred microcapsule, its prescription is as follows:
Particularly preferred microcapsule, its prescription is as follows:
Preferred microcapsule, its prescription is as follows:
Most preferred microcapsule, its prescription is as follows:
Or
Above-mentioned slow-releasing microcapsule of the present invention is very stable in acid medium, but can gradually discharge the N-CWS medicine in neutral medium, thereby can complete maintenance efficacy of drugs when oral.Above-mentioned slow-releasing microcapsule of the present invention has following advantage:
1) absorption of intestinal location and intestinal location absorb;
2) the high envelop rate of N-CWS and high carrying drug ratio;
3) drug releasing rate can be by the THICKNESS CONTROL of cyst wall;
4) technique is simple, and is easy to operate, and favorable reproducibility has a good application prospect.
The present invention also comprises micron order or submicron order N-CWS medicament slow release microcapsule is mixed with adjuvant, is prepared into the slow-releasing microcapsule preparation, such as capsule, tablet, granule etc.
Three kinds of novel forms of preparation N-CWS are below described respectively: slow releasing capsule, tablet and granule, comprising as the N-CWS medicament microcapsule of effective ingredient and slow releasing capsule figuration adjuvant, tablet figuration adjuvant, the granule figuration adjuvant pharmaceutically approved.
The described figuration adjuvant of tablet comprises: microcrystalline Cellulose, pregelatinized Starch, polyvidone (polyvinylpyrrolidone), cross-linking sodium carboxymethyl cellulose, magnesium stearate.Wherein every of the content of N-CWS is 400 μ g～1000 μ g, and every in tablet all is heavy 90～110 mg.
Method for preparing tablet thereof is characterized in that the method comprises the steps:
The polyvidone of N-CWS medicament microcapsule, pregelatinized Starch and Nei Jia is pulverized altogether, then be dry mixed with the waterless adhesive microcrystalline Cellulose, the mixture that previous step is made is configured to aqueous solution soft material processed with the polyvidone that adds, 20 mesh sieves are granulated, with the particulate low-temperature freeze drying that makes, 18 mesh sieve granulate; In granule, add magnesium stearate lubricant, mix homogeneously, the qualified rear tabletting of intermediate, and get final product.
Wherein adjuvant is grouped into by the one-tenth of following percentage by weight:
Therefore, adopted above-mentioned technical scheme after so that tablet has enough hardness and outstanding releasing properties, in addition, employed adjuvant is cheap, safe and reliable, is convenient to industrialization and clinical use.
The described figuration adjuvant of slow releasing capsule comprises: lactose, starch, dextrin, PEG-2000, menthol.Wherein every of the content of N-CWS is 400 μ g～1000 μ g.Its preparation method comprises
N-CWS medicament microcapsule, adjuvant are dry mixed the aqueous solution that adds soft material processed together, and 20 mesh sieves are granulated, with the particulate low-temperature freeze drying that makes, and 18 mesh sieve granulate; In granule, add magnesium stearate lubricant, mix homogeneously, intermediate is qualified rear encapsulated, and get final product.
The described figuration adjuvant of granule comprises: sodium carbonate, sucrose, cocoanut flavour, PVP K30.Wherein every bag of the content of N-CWS is 400 μ g～1000 μ g.
Process for producing granula is characterized in that, in per 1000 bags of granule agent, contains N-CWS190-790 mg, sodium carbonate 40-169g; Sucrose 730-2900g; 5% PVP K30 65-270mL; Cocoanut flavour 0.18-0.75g.
Slow-releasing microcapsule prescription of the present invention and preparation method obtain through screening, and screening process is as follows:
From following 5 prescriptions, select
Screening index:
| ? | The burst release rate | Stability | Mobile | The size of microcapsule |
| Prescription 1 | 44.5% | Well | Well | 0.5?μm |
| Prescription 2 | 56.2% | Generally | Generally | 1.0?μm |
| Prescription 3 | 49.1% | Generally | Well | 2.0?μm |
| Prescription 4 | 58.8% | Generally | Generally | 5.0?μm |
| Prescription 5 | 13.6% | Well | Well | 10.0?μm |
The result shows Lyopgized Nocardia rubra-cell Wall Skeleton slow-releasing microcapsule prescription 5, and its burst release rate is lower, have good stability, being of moderate size of good fluidity and microcapsule.
Illustrate that for better product of the present invention is in the advantage aspect stability and the storage, get according to embodiment 3, embodiment 4, embodiment 5 methods and prepare respectively Lyopgized Nocardia rubra-cell Wall Skeleton slow releasing capsule, tablet, granule, by simulation listing fractional pack, place the stable case of 25 ℃ ± 2 ℃ of temperature, RH60% ± 10%, respectively at sampling in 3,6,9,12 months, measure indices, the results are shown in Table 1, table 2, table 3.
Table 1: embodiment 1 N-CWS(400 μ g) slow releasing capsule stability test result
| The investigation project | 0 month | March | June | JIUYUE | December |
| Moisture (%) | 1.7 | 1.8 | 2.0 | 2.2 | 2.3 |
| Sugar content (μ g) | 69 | 68.8 | 68.7 | 68.6 | 68.6 |
| Tumour inhibiting rate (%) | 70.8 | 70.8 | 70.5 | 70.4 | 70.4 |
Table 2: embodiment 2 N-CWS(400 μ g) tablet stability result of the test
| The investigation project | 0 month | March | June | JIUYUE | December |
| Moisture (%) | 1.6 | 1.8 | 1.9 | 2.0 | 2.2 |
| Sugar content (μ g) | 72 | 71.8 | 71.6 | 71.6 | 71.5 |
| Tumour inhibiting rate (%) | 78.0 | 77.6 | 77.5 | 77.8 | 77.4 |
Table 3: embodiment 1 N-CWS(400 μ g) granule stability test result
| The investigation project | 0 month | March | June | JIUYUE | December |
| Moisture (%) | 1.8 | 1.9 | 2.1 | 2.3 | 2.4 |
| Sugar content (μ g) | 70.8 | 70.6 | 70.6 | 70.6 | 70.5 |
| Tumour inhibiting rate (%) | 73.8 | 73.0 | 73.5 | 73.4 | 73.2 |
The result shows that Lyopgized Nocardia rubra-cell Wall Skeleton slow releasing capsule, tablet, granule placed 12 months under 25 ℃ ± 2 ℃, RH60% ± 10% condition, its sugared content and pharmaceutically active do not change substantially, have good stability.
The specific embodiment
Further specify the present invention below by several specific embodiments, do not consist of the restriction of the claimed scope of the present invention for the concrete data that relate among the embodiment and operation etc.
The preparation of embodiment 1 N-CWS slow-releasing microcapsule agent is achieved in that
The microcapsule prescription:
(1) because of the former powder of the N-CWS both water insoluble solvents such as DMSO that also are insoluble to, and the principal agent powder is superfine, in prescription, add suitable oil medium, after the abundant moistening of N-CWS, add successively tween 80, Osmitrol, adopt supercritical ultrasonics technology to prepare N-CWS suspendible emulsion, filter with low-speed centrifugal or sand core filter and remove black precipitate and emulsifying N-CWS granule completely not, with the uniform N-CWS suspendible of gained emulsion, make lyophilized powder through vacuum lyophilization.
(2) N-CWS lyophilized powder medicine is placed the saline solution (pH is between 1 ~ 6) of 0.01 ~ 10M of the polyanion that contains 0.01 ~ 100 mg adsorb 0.1 ~ 100 min;
(3) centrifugal or remove by filter the polyanion that is not adsorbed, with saline solution (pH is between 1 ~ 6) repeated washing of 0.01 ~ 10M for several times, wash 0.1 ~ 100 min at every turn;
(4) again the microcapsule that makes is placed the saline solution (pH is between 1 ~ 6) of 0.01 ~ 10M of the polycation that contains 0.01 ~ 100 mg/mL to adsorb 0.1 ~ 100 min;
(5) centrifugal or remove by filter the polycation that is not adsorbed, with saline solution (pH is between 1 ~ 6) repeated washing of 0.01 ~ 10M for several times, wash 0.1 ~ 100 min at every turn;
(6) repeating step (2) namely obtains having assembled the high molecular N-CWS medicament microcapsule of the different numbers of plies to (5) successively.
In the present embodiment, the polymer number of plies can be 1 ~ 50 layer.
The preparation of embodiment 2 N-CWS slow-releasing microcapsules is achieved in that
The microcapsule prescription:
(1) with after the abundant moistening of the former powder of N-CWS, add successively tween 80, Osmitrol, adopt supercritical ultrasonics technology to prepare N-CWS suspendible emulsion, filter with low-speed centrifugal or sand core filter and to remove black precipitate and emulsifying N-CWS granule completely not, with the uniform N-CWS suspendible of gained emulsion, make lyophilized powder through vacuum lyophilization.
(2) N-CWS lyophilized powder medicine is placed kayexalate solution (0.001 ~ 100mM hydrochloric acid solution contains the inorganic salt of 0.01 ~ 10M) absorption 0.1 ~ 100 min that contains 0.01 ~ 100 mg/mL;
(3) the centrifugal kayexalate that is not adsorbed of removing, the 0.001 ~ 100mM saline solution repeated washing several with the inorganic salt that contains 0.01 ~ 10M washs 0.1 ~ 100 min at every turn;
(4) again the microcapsule that makes is placed PAH solution (0.001 ~ 100mM hydrochloric acid solution contains the inorganic salt of 0.01 ~ 10M) absorption 0.1 ~ 100 min that contains 0.01 ~ 100 mg/mL;
(5) the centrifugal PAH that is not adsorbed of removing, the 0.001 ~ 100mM hydrochloric acid solution repeated washing several with the inorganic salt that contains 0.01 ~ 10M washs 0.1 ~ 100 min at every turn;
(6) repeating step (2) namely obtains having assembled the high molecular N-CWS medicament microcapsule of the different numbers of plies to (5) successively.
Present embodiment step 2) in, the concentration of kayexalate solution is preferably 1 mg/mL.
In the present embodiment step 3), cleaning mixture is preferably the hydrochloric acid solution of sodium chloride-containing.
In the present embodiment step 4), the concentration of PAH solution is preferably 1 mg/mL.
In the present embodiment step 5), cleaning mixture is preferably the hydrochloric acid solution of sodium chloride-containing.
The preparation of embodiment 3 N-CWS slow releasing capsule is achieved in that
Prescription (1000):
Preparation technology: the supplementary material of above-mentioned recipe quantity is granulated, granulate, drying, encapsulatedly got final product to such an extent that contain the capsule of N-CWS microcapsule.
The preparation of embodiment 4 N-CWS tablets is achieved in that
Prescription (1000):
Preparation technology: the supplementary material of above-mentioned recipe quantity is dry mixed; With the aqueous solution soft material processed that the polyvidone that adds is configured to, 20 mesh sieves are granulated, dry, granulate; The magnesium stearate that adds again recipe quantity, mix homogeneously, intermediate detect qualified rear tabletting, namely get the tablet of N-CWS microcapsule.
The preparation of embodiment 5 N-CWS granules is achieved in that
Prescription (1000 bags):
Preparation technology: first sucrose is pulverized, taken by weighing respectively through 80 mesh sieves sucrose, sodium carbonate later by recipe quantity and make mixed accessories.After measuring the N-CWS slow-releasing microcapsule and this mixed accessories mixes by prescription, place in the lump pulverizer, be dry mixed evenly.Add the 5% PVP K30 solution (with the preparation of 50% ethanol solvent) of recipe quantity, make soft material.Soft material is granulated with 12 mesh sieves, and again in 25 ℃ of vacuum dryings, 12 order granulate, the granule that granulate is good add cocoanut flavour (having crossed 80 mesh sieves) mix homogeneously.
Embodiment 6
The preparation of N-CWS slow-releasing microcapsule is achieved in that
Preparation method is with embodiment 1.
Embodiment 7
The preparation of N-CWS slow-releasing microcapsule is achieved in that
Preparation method is with embodiment 1.
Claims (10)
1. a slow-releasing microcapsule preparation that contains Lyopgized Nocardia rubra-cell Wall Skeleton is characterized in that, its prescription of described slow-releasing microcapsule is as follows:
Its preparation method is as follows:
1) first the former powder of N-CWS is prepared into N-CWS suspendible emulsion, filter removes black precipitate and emulsifying N-CWS granule completely not, obtain uniform N-CWS suspendible emulsion, lyophilized powder is made in vacuum lyophilization,
2) take N-CWS lyophilizing powder as template particles; adopting the biocompatibility macromolecule of two kinds of oppositely chargeds is the wall material; the principle that attracts each other according to the xenogenesis electric charge; these two kinds of macromolecular material one decks are combined with being close to one deck; surface at the lyophilizing powder of N-CWS forms as thin as a wafer protectiveness adventitia; obtain the N-CWS slow-releasing microcapsule
Wherein, used wetting agent is selected from: purified water
Wherein emulsion is selected from: Arlacel-80, tween 80, mannitol, and their aqueous solution, if their aqueous solution, its compound method is as follows: corresponding emulsifying agent is added in an amount of purified water, and emulsifying agent accounts for 12% ~ 25% of emulsion,
Polycation is selected from, such as one or more the mixture in chitosan, protamine, poly arginine, PAH, collagen, poly-D-lysine, cation dextran, diphenylamines-4-diazo resin, substituted diphenylamine diazo resin or other the positively charged macromolecular materials
Polyanion is selected from, such as one or more the mixture in seaweeds sodium, dextran sulfate, heparin, heparin sulfate, polyglutamic acid, sodium carboxymethyl cellulose, polyanion cellulose, kayexalate, chondroitin sulfate, hyaluronic acid or other the electronegative macromolecular materials
Wherein, described saline solution be selected from sodium chloride, ammonium chloride, ammonium sulfate, potassium sulfate, sodium sulfate, potassium chloride,
The solution of sodium phosphate or other strong electrolytes, preferred their hydrochloric acid solution, its compound method is as follows: corresponding salt is added in an amount of purified water, and concentration of salt solution is 0.01 ~ 10M.
2. slow-releasing microcapsule preparation according to claim 1 is characterized in that, described slow-releasing microcapsule its preparation method is as follows:
(1) with oil medium with the N-CWS moistening, add emulsion, preparation N-CWS suspendible emulsion filters and removes black precipitate and emulsifying N-CWS granule completely not, with the uniform N-CWS suspendible of gained emulsion, makes lyophilized powder through vacuum lyophilization,
(2) place the saline solution that contains polyanion to adsorb N-CWS lyophilized powder medicine, remove the polyanion that is not adsorbed, with the saline solution washing, place the saline solution that contains polycation to adsorb the microcapsule that makes, remove the polycation that is not adsorbed, wash with saline solution; The above-mentioned adsorption step of repeating step namely obtains having assembled the high molecular N-CWS medicament microcapsule of the different numbers of plies.
3. slow-releasing microcapsule preparation according to claim 1 is characterized in that, its prescription of described slow-releasing microcapsule is as follows:
4. slow-releasing microcapsule preparation according to claim 1 is characterized in that, its prescription of described slow-releasing microcapsule is as follows:
5. slow-releasing microcapsule preparation according to claim 1 is characterized in that, its prescription of described slow-releasing microcapsule is as follows:
Or
6. slow-releasing microcapsule preparation according to claim 1 is characterized in that, described preparation is selected from capsule, tablet, granule.
7. slow-releasing microcapsule preparation according to claim 1, described tablet, it is as follows to fill a prescription: the N-CWS medicament microcapsule, microcrystalline Cellulose, pregelatinized Starch, polyvidone, cross-linking sodium carboxymethyl cellulose, magnesium stearate, wherein every of the content of N-CWS is 400 μ g～1000 μ g, every in tablet all is heavy 90～110 mg, its preparation method is as follows: with the N-CWS medicament microcapsule, the polyvidone of pregelatinized Starch and Nei Jia is pulverized altogether, then be dry mixed with the waterless adhesive microcrystalline Cellulose, the mixture that previous step is made is configured to aqueous solution soft material processed with the polyvidone that adds, 20 mesh sieves are granulated, with the particulate low-temperature freeze drying that makes, 18 mesh sieve granulate; In granule, add magnesium stearate lubricant, mix homogeneously, the qualified rear tabletting of intermediate, and get final product.
8. slow-releasing microcapsule preparation according to claim 1, described tablet, wherein adjuvant is grouped into by the one-tenth of following percentage by weight:
9. slow-releasing microcapsule preparation according to claim 1, described capsule, it is as follows to fill a prescription: N-CWS medicament microcapsule, lactose, starch, dextrin, PEG-2000, menthol, wherein every of the content of N-CWS is 400 μ g～1000 μ g, its preparation method is as follows: N-CWS medicament microcapsule, adjuvant are dry mixed the aqueous solution that adds soft material processed together, 20 mesh sieves are granulated, with the particulate low-temperature freeze drying that makes, and 18 mesh sieve granulate; In granule, add magnesium stearate lubricant, mix homogeneously, intermediate is qualified rear encapsulated, and get final product.
10. slow-releasing microcapsule preparation according to claim 1, described granule, it is as follows to fill a prescription: N-CWS190-790 mg, sodium carbonate 40-169g; Sucrose 730-2900g; 5% PVP K30 65-270mL; Cocoanut flavour 0.18-0.75g.
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| CN105709214A (en) * | 2016-02-03 | 2016-06-29 | 华侨大学 | Slow-release pharmaceutical preparation of long-acting follicle-stimulating hormone |
| CN105727260A (en) * | 2016-02-03 | 2016-07-06 | 华侨大学 | Long-acting preparation of follicle-stimulating hormone |
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| CN105709214A (en) * | 2016-02-03 | 2016-06-29 | 华侨大学 | Slow-release pharmaceutical preparation of long-acting follicle-stimulating hormone |
| CN105727260A (en) * | 2016-02-03 | 2016-07-06 | 华侨大学 | Long-acting preparation of follicle-stimulating hormone |
| CN105709214B (en) * | 2016-02-03 | 2020-08-07 | 华侨大学 | Sustained-release pharmaceutical preparation of long-acting follicle-stimulating hormone |
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