CN103845293A - Lutein pellet and preparation method thereof - Google Patents

Abstract

The invention provides a lutein pellet, which is prepared from lutein and a pharmaceutic adjuvant. The lutein pellet is characterized in that the pharmaceutic adjuvant is an excipient and an adhesive, wherein the pellet preparation contains 5-20% of lutein, 70-85% of excipient and 1-5% of adhesive. The lutein pellet disclosed by the invention is high in dissolution rate, and high in bioavailability, and the preparation method is simple, convenient and easy to operate.

Description

A kind of lutein micropills and preparation method thereof

Technical field

The present invention relates to medicine food technical field, be specifically related to micropill that a kind of phylloxanthin makes and preparation method thereof.

Background technology

Phylloxanthin and zeaxanthin are the key components that forms the plant pigment such as vegetable, fruit, flowers, are also the main pigments that forms human eye retina's macular region.The phylloxanthin that the mankind's eyes contain a large amount, this element is that human body cannot be manufactured, and must supplement by taking in phylloxanthin, if lack this element, eyes will be blind.Foreign study shows: phylloxanthin can prevent eyes photic damage, prevent because phylloxanthin lacks the visual deterioration and the blind disease that cause, and because of body aging cause cardiovascula sclerosis, coronary heart disease and tumor disease.It is the chief component material that eye retina, macula lutea can not lack; Prevent physiological structure and the function variation of eyes; Be a kind of potent antioxidant, absorb ultraviolet, blue light, dissolve eyes light poisoning at all; There is vasodilation function, improve optical fundus blood microcirculation, promote nutrient substance supply.

At present, be deeply subject to consumers in general's approval about the product of phylloxanthin, these products are common Tablet and Capsula agent substantially, but above-mentioned dosage form exists disintegration time long; A certain position point disintegrate in vivo, has certain zest to gastric mucosa; The shortcomings such as bioavailability is low.Based on the problems referred to above, we will develop micropill technology transfer rapidly to field of food at field of medicaments, this product made and discharged in vivo micro-pill type product controlled and that bioavailability is high, to meet better consumers in general's demand.

In the preparation process of pellet preparations, generally to add the pharmaceutic adjuvants such as excipient, binding agent, porogen, disintegrating agent, plasticizer [" design and development of sustained-release and controlled release preparation " Yan Yaodong etc., Chinese Medicine science and technology publishing house, 2006,257-258], in the research process of micropill, need to carry out deep research to preparation preparation, just can prepare qualified micropill product.

Summary of the invention

For these reasons, we carry out deep analysis by the physics and chemistry character to phylloxanthin, take dissolution as index, by the test of science, determine that pharmaceutic adjuvant is excipient and binding agent, and excipient and binding agent are carried out to determining of weight percentage: " pharmaceutic adjuvant is excipient and binding agent, and its pellet preparations Lutein weight percentage is 5～20%; the weight percentage of excipient is 70～85%, and the weight percentage of binding agent is 1～5% "; By this complete technical scheme, those skilled in the art, according to the preparation method of the micropill of prior art, just can prepare satisfactory pellet preparations; Above-mentioned pellet preparations can be prepared into satisfactory slow releasing preparation or enteric coated preparation, be conducive to user's compliance.Phylloxanthin and excipient have been carried out sufficient pulverizing by we, be that micronization is pulverized, phylloxanthin has been distributed in excipient well, make particle diameter reach micro powder grade, make micropill with such material, in the process discharging in vivo, main constituent can discharge rapidly along with the dissolving of excipient, and this product is made up of the little micropill unit of hundreds of grain, disperse in vivo area large, the specific surface area that contacts of organ is also large with absorbing, therefore it is rapid to make this product take rear onset, bioavailability is high.

The object of the invention is, in order to overcome the problems of the prior art, provides a kind of novel formulation of phylloxanthin---pellet preparations.

Another object of the present invention is to provide a kind of preparation method of lutein micropills preparation, the method is simple, convenient, easy operating.

Phylloxanthin of the present invention can be extract, can be also effective ingredient, prepares according to existing literature method or patented method.

The object of the invention is to be achieved through the following technical solutions:

A kind of lutein micropills preparation, be prepared from by phylloxanthin, pharmaceutic adjuvant, it is characterized in that pharmaceutic adjuvant is excipient and binding agent, its pellet preparations Lutein weight percentage is 5～20%, the weight percentage of excipient is 70～85%, and the weight percentage of binding agent is 1～5%.

Slow release formulation prepared by above-mentioned lutein micropills preparation.

Or the enteric dosage form prepared of above-mentioned lutein micropills preparation.

Wherein said excipient is one or more the mixture being selected from sucrose, dextrin, starch, microcrystalline Cellulose, lactose, methylcellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone, ethyl cellulose, acrylic resin, hydroxypropyl emthylcellulose and gelatin.

Wherein said binding agent is one or more the mixture in polyvinylpyrrolidone, cellulose family, resinae, saccharide, animal acid.

Pellet preparations of the present invention can, according to technique scheme, be prepared with the preparation method of prior art pellet preparations, also can be prepared by the following method:

(1) get phylloxanthin, add excipient, be crushed to micronized rank, mix;

(2) by the solution in water-soluble binding agent, dehydrated alcohol or aquiferous ethanol;

(3) adopt micropill forming technique to make micropill.

Wherein said micropill forming technique comprises agitation procedure, method of extruding and kneading to pellets or the centrifugal fluidized granulation method of being selected from.

In conventional art, the degree of grinding of medical material or extract is coarse powder (inside take, particle diameter 850um ± 70um, cross 24 mesh sieves), middle powder (inside take, particle diameter 250um ± 9.9um, cross 65 mesh sieves), fine powder (wound use, particle diameter 150um ± 6.6um, cross 100 mesh sieves), fine powder (eye dripping use, particle diameter 125um ± 5.8um, 120 mesh sieves) and impalpable powder (particle diameter 75um ± 4.1um, 200 mesh sieves), the present invention adopts micronization technology that phylloxanthin is ground into micropowder, its mean diameter is generally less than 10um, is mainly distributed in 1～20um.Method of micronization can adopt method of the prior art: physical pulverization method, such as mechanical impact crusher, jet mill, ball mill, vibromill, stirring mill, Raymond mill, high-pressure pulverizer etc.; Physical chemistry synthetic method, comprising that spraying is dry, original position micronization and supercritical fluid technology etc.Compared with traditional crushing technology, this technique main advantage is: increase effective ingredient absorbance, improve bioavailability.The dissolution rate of effective ingredient is directly proportional to its specific grain surface is long-pending, and specific surface area and particle diameter are inversely proportional to.Therefore, the particle diameter of effective ingredient is thinner, and its specific surface area is larger, more contributes to the stripping of effective ingredient.According to the study, the intestines and stomach is 15um left and right to the optimal absorption granularity of material grains, and the granule of micron composition has just reached this optimal absorption fineness level; Because micron order effective ingredient obviously increases at gastrointestinal dissolubility, thereby increase its bioavailability, accelerated its onset time.

Micropill forming technique in the present invention can adopt any micropill forming technique of the prior art, and these technology include but not limited to: agitation procedure, method of extruding and kneading to pellets or centrifugal fluidized granulation method etc.

Beneficial effect of the present invention is:

First, phylloxanthin and excipient have been carried out sufficient pulverizing by we, phylloxanthin has been distributed in excipient well, and particle diameter reached micro powder grade, make micropill with such material, in the process discharging in vivo, main constituent can discharge rapidly along with the dissolving of excipient, and the every capsules of this product is made up of the little micropill unit of hundreds of grain, disperse in vivo area large, the specific surface area contacting with gastric juice is also large, admittedly it is rapid to make this product take rear onset, bioavailability is high.

The micropill that micropill of the present invention can be made quick release or be discharged at a slow speed by different prescriptions as required, belongs to multiple agent type, can be made up of the micropill of different drug release rates.Also can pass through packaging technique, micropill is made to the positioned releasing micropills such as stomach dissolution type, enteric solubility.This micropill can encapsulatedly be made capsule, or tabletting makes tablet, or makes other various packaged forms.Micropill of the present invention is compared with single dose dosage form (as tablet), and supplementary product consumption is few, and steady quality has good curative effect repeatability, and adverse reaction rate is low; This product micropill increases at the area of gastrointestinal tract surface distributed, bioavailability is improved and local excitation is less or eliminate, and selects for consumers in general provide more consumption.

This product and commercially available tablet and conventional capsule agent have been carried out release in vitro contrast test (experimental technique is according to Pharmacopoeia of People's Republic of China version dissolution determination method in 2005) by we, and result is as follows:

Conventional capsule agent (Xi'an manufacturer production, lot number: 100203) 30 minutes dissolution rates are 62% in gastric juice;

Tablet (Guangzhou manufacturer production, lot number: 110205) 30 minutes dissolution rates are 60% in gastric juice;

And this product 25 minutes dissolution rates in gastric juice reach 92%.

Meanwhile, we can also, by micropill being carried out to the technology of coating, by different coating materials, make product become the product of the different sizes such as slow release, controlled release, enteric.

We make this product after slow-release micro-pill, have the slow-release function of 12 hours, therefore can effectively control the burst size of phylloxanthin, and safety, effectiveness are better; Slow-release micro-pill can make blood drug level reach rapidly curative effect concentration, and maintains steady, long valid density, and blood concentration fluctuation is little; This product has reduced the accumulated dose of taking than common dosage form simultaneously, has reduced the number of times of taking of consumer.We find this product by release in vitro simulation test, its release profiles is obvious, and in the time of 2h, release is more than 25%; When 5h, release is more than 50%; When 8h, release is more than 75%; When 12h, release is more than 95%.

The consumer that has gastric lesions for some, the impact for fear of product on stomach makes this product be absorbed by the body better simultaneously, and we can also make enteric coated preparation by this product, by micropill is carried out to enteric coated technology, make product reach the object of enteric.This enteric coated micropill is carried out the discovery of release in vitro simulation test by we, micropill in simulated gastric fluid 2 hours without any stripping, outward appearance is also without any variation, and in the time that we are put into its taking-up in simulated intestinal fluid dissolution test, its 30 minutes releases have just reached more than 90%.

 

The specific embodiment

 

embodiment 1

Get the raw material for standby of following formula

Phylloxanthin	15g(is in sterling)
		Celluloasun Microcrystallisatum	81
Hydroxypropyl emthylcellulose	4g

Prepare in accordance with the following methods pellet preparations:

(1) phylloxanthin of getting above-mentioned formula ratio adds Celluloasun Microcrystallisatum, is crushed to micronization rank with ball mill, mixes;

(2) hydroxypropyl emthylcellulose is dissolved in to 75% alcoholic solution;

(3) adopt method of extruding and kneading to pellets to make micropill.

embodiment 2

Get the raw material for standby of following formula

Phylloxanthin	10g(is in sterling)
		Starch	85g
Polyvinylpyrrolidone	5g

Prepare in accordance with the following methods pellet preparations:

(1) phylloxanthin of getting above-mentioned formula ratio adds starch, is crushed to micronization rank with ball mill, mixes;

(2) polyvinyl pyrrolidone is soluble in water;

(3) adopt agitation procedure to make micropill.

embodiment 3

Get the raw material for standby of following formula

Phylloxanthin	8g(is in sterling)
		Sucrose	54
Starch	34g
		Polyvinylpyrrolidone	4g

Prepare in accordance with the following methods pellet preparations:

(1) phylloxanthin of getting above-mentioned formula ratio adds sugarcane sugar and starch, is crushed to micronization rank with ball mill, mixes;

(2) polyvinylpyrrolidone is dissolved in suitable quantity of water;

(3) adopt centrifugal fluidized granulation method to make micropill.

Claims (7)

1. a lutein micropills preparation, be prepared from by phylloxanthin, pharmaceutic adjuvant, it is characterized in that pharmaceutic adjuvant is excipient and binding agent, its pellet preparations Lutein weight percentage is 5～20%, the weight percentage of excipient is 70～85%, and the weight percentage of binding agent is 1～5%.

2. the slow release formulation that prepared by a kind of lutein micropills preparation according to claim 1.

3. the enteric dosage form that prepared by a kind of lutein micropills preparation according to claim 1.

4. a kind of lutein micropills preparation according to claim 1, wherein said excipient is one or more the mixture being selected from sucrose, dextrin, starch, microcrystalline Cellulose, lactose, methylcellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone, ethyl cellulose, acrylic resin, hydroxypropyl emthylcellulose and gelatin.

5. a kind of lutein micropills preparation according to claim 1, wherein said binding agent is one or more the mixture in polyvinylpyrrolidone, cellulose family, resinae, saccharide, animal acid.

6. according to the preparation method of a kind of lutein micropills preparation described in claim 1～5 any one, the steps include:

(1) get phylloxanthin, add excipient, be crushed to micronized rank, mix;

(2) by the solution of water-soluble binding agent, dehydrated alcohol or aquiferous ethanol;

(3) adopt micropill forming technique to make micropill.

7. preparation method according to claim 6, wherein said micropill forming technique comprises agitation procedure, method of extruding and kneading to pellets or the centrifugal fluidized granulation method of being selected from.