| United States Patent |
5,578,307 |
| Wunderlich , et al. |
November 26, 1996 |
Shaped articles containing plant extract(s), in particular pellets, are
formed by dispersing the plant extract(s) in a matrix predominantly composed of
a skeleton builder, i.e. collagen, gelatin, fractionated gelatin, a collagen
hydrolysate, a gelatin derivative, plant protein or plant protein hydrolysate.
They are storage-stable, and their pharmacological and cosmetic characteristics
are essentially unaltered in comparison with the native extract. They are
prepared by a simple process in which liquid plant extract(s) is(are) mixed or
emulsified in a solution of the skeleton builder, or solid extracts are
dissolved or suspended in a solution of the skeleton builder, the dispersion of
skeleton builder and plant extract(s) is added dropwise to an intensely cold,
inert, liquefied gas, preferably liquid nitrogen, thus shaping the pellets, and
the shaped pellets are dried. The plant extract employed is preferably Aloe vera
juice.
| Inventors: |
Wunderlich; Jens-Christian
(Heidelberg, DE); Schick; Ursula (Schriesheim, DE); Werry;
Jurgen (Ludwigshafen, DE); Freidenreich; Jurgen (Schriesheim,
DE) |
| Assignee: |
Alfatec-Pharma GmbH (Heidelberg, DE) |
| Appl. No.: |
256651 |
| Filed: |
October 18, 1994 |
| U.S. Class: |
424/195.1; 424/451;
424/456; 424/464; 424/484; 424/485; 424/486; 424/487; 424/488; 424/492;
424/520 |
| Intern'l Class: |
A61K 035/78; A61K 009/127; A61K
009/64; A61K 009/14 |
| Field of Search: |
424/195.1,451,456,464,484,485,486,487,488,492,520 |
References Cited [Referenced
By]
U.S. Patent Documents
| Foreign Patent Documents |
| 770604 |
Dec., 1971 |
BE |
. |
| 1259081 |
Mar., 1961 |
FR. |
|
| 1397583 |
Mar., 1965 |
FR |
. |
| 454386 |
Jan., 1928 |
DE |
. |
| 242323 |
Dec., 1925 |
GB |
. |
Other References
|
Chem Abstrs. 1/3(13):1/4127d, 1990. |
Primary Examiner: Rollins; John W.
Attorney, Agent or Firm: Burns, Doane, Swecker & Mathis
Claims
1. A shaped article containing plant extract, which comprises a dispersion
of the plant extract in a matrix composed predominantly of a skeleton
builder of hydrophilic macromolecules selected from the group consisting of:
collagen, gelatin, fractionated gelatin, collagen hydrolysates, gelatin
derivatives, elastin hydrolysates, plant proteins, plant protein
hydrolysates and mixtures thereof, wherein the shaped article contains 0.1
to 98% by weight of said plant extract.
2. A shaped article as claimed in claim 1, wherein the hydrophilic
macromolecule comprises a thermoreversible sol/gel forming agent.
3. A shaped article as claimed in claim 2, wherein the sol/gel forming agent
is a gelatin whose molecular weight distribution has a maximum of above
10.sup.5 D.
4. A shaped article as claimed in claim 1, wherein the matrix contains an
additional skeleton builder from the group consisting of: albumins,
agar-agar, gum arabic, pectins, tragacanth, xanthan, natural and modified
starches, dextrans, dextrins, maltodextrin, chitosan, alginates, cellulose
derivatives, dextran, sugars, glycine, lactose, sorbitol, mannitol or
polyvinylpyrrolidone.
5. A shaped article as claimed in claim 4, wherein the matrix contains less
than 50% by weight of additional skeleton builder.
6. A shaped article as claimed in claim 1, which further comprises a
pharmaceutically acceptable auxiliary or carrier for the matrix.
7. A shaped article as claimed in claim 1, which contains 0.1-60% by weight
of plant extract.
8. A shaped article as claimed in claim 1, wherein the plant extract is
selected from the group consisting of:
solid plant extracts, liquid plant extracts, hydrophilic plant extracts,
lipophilic plant extracts, individual plant constituents and mixtures
thereof.
9. A shaped article as claimed in claim 1, wherein the plant extract is Aloe
vera juice.
10. A shaped article as claimed in claim 1, in the form of a lyophilisate.
11. A shaped article as claimed in claim 1, which is rapidly dissolving and
wherein the matrix is composed of essentially a plant protein, plant protein
hydrolysate, collagen hydrolysate, a gelatin derivative which is soluble in
cold water, or gelatin whose molecular weight distribution has a maximum of
below 10.sup.5 D.
12. A shaped article as claimed in claim 1, further comprising (1) a
plasticizer selected from glycerol and sorbitol and (2) masking flavors
wherein the plasticizer and masking flavors comprise 1-50% by weight of the
shaped article.
13. A shaped article as claimed in claim 12, in solid, semi-solid or
gel-like form.
14. A shaped article as claimed in claim 13, in the form of a pellet.
15. A shaped article containing Aloe vera juice, which comprises a
dispersion of the Aloe vera juice in a matrix predominantly composed of
skeleton builders of hydrophilic macromolecules selected from the group
consisting of: collagen, gelatin, fractionated gelatin, collagen
hydrolysates, gelatin derivatives, plant proteins, plant protein
hydrolysates, elastin hydrolysates and their mixtures, wherein said shaped
article contains 0.1 to 98% by weight of said Aloe vera juice.
16. A process for the preparation of shaped articles containing plant
extract, wherein
a) a skeleton builder of hydrophilic macromolecules selected from the group
consisting of: collagen, gelatin, fractionated gelatin, collagen
hydrolysates, gelatin derivatives, plant proteins, plant protein
hydrolysates, elastin hydrolysates and mixtures thereof, is mixed with plant
extracts selected from the group consisting of: hydrophilic liquid plant
extracts, aqueous extracts, alcoholic extracts, and mixtures thereof to
produce a mixture that comprises a dispersion of the plant extract in a
matrix of said skeleton builder; and
b) the resulting mixture of skeleton builder and plant extract is added
dropwise to an intensely cold inert liquefied gas, thus making it into
shaped articles, wherein the mixture is added at a temperature and pressure
effective to form drops of said mixture and wherein each of said shaped
articles contains 0.1 to 98% by weight of said plant extract.
17. A process as claimed in claim 16, wherein the skeleton builder comprises
a sol/gel forming agent.
18. A process as claimed in claim 16, wherein the shaped article prepared is
a pellet.
19. A process as claimed in claim 18, wherein the pellets are freeze-dried.
20. A process as claimed in claim 16, wherein the plant extract employed is
Aloe vera juice.
21. A process as claimed in claim 20 wherein the resulting mixture obtained
in step b) is added dropwise into a bath having a temperature of
-108.degree. C. to -210.degree. C.
22. A process as claimed in claim 16, wherein step b) produces pellets that
are thereafter incorporated into a cream or hydrogel base.
23. A process as claimed in claim 16, wherein step a) comprises preparing a
solution of the skeleton builder and mixing the hydrophilic liquid plant
extract into said solution.
24. A process as claimed in claim 16, wherein the plant extracts comprise
alcoholic extracts said process further comprising the step of removing
alcohols from the mixture formed in step a).
25. A process as claimed in claim 16, wherein step a) comprises
concentrating the mixture formed.
26. A process as claimed in claim 16, wherein a lipophilic extract is
emulsified in the matrix, or a solid plant extract is suspended or dissolved
in the matrix in step a).
27. A process as claimed in claim 16, wherein step b) comprises adding the
resulting mixture into liquid nitrogen.
28. A process as claimed in claim 16, wherein an additional skeleton builder
from the group consisting of: albumin, agar-agar, gum arabic, pectins,
tragacanth, xanthan, natural and modified starches, dextrans, dextrins,
maltodextrin, chitosan, alginates, cellulose derivatives, dextran, sugars,
glycine, lactose, mannitol or polyvinylpyrrolidone is added to the
dispersion of skeleton builder and plant extract.
29. A process as claimed in claim 18 wherein the resulting mixture obtained
in step b) is added dropwise into a bath having a temperature of
-108.degree. C. to -210.degree. C.
30. A process as claimed in claim 16, wherein the mixture produced in step
a) further comprises a plasticizer selected from glycerol, sorbitol and
mixtures thereof wherein the plasticizer comprises 1-50% by weight of said
mixture.
31. A process as claimed in claim 16, wherein gelatin whose molecular weight
distribution has a maximum of above 10.sup.5 D is mixed with the plant
extract at not more than 60.degree. C. to act as skeleton builder.
32. A process as claimed in claim 31, wherein step a) comprises mixing
liquid Aloe vera juice with gelatin at not more than 40.degree. C.
33. A process as claimed in claim 16 further comprising the step of drying
the shaped articles produced in step b) at not more than 50.degree. C.
34. A process as claimed in claim 16 wherein the resulting mixture obtained
in step b) is added dropwise into a bath having a temperature of
-108.degree. C. to -210.degree. C.
35. A pharmaceutical dosage form containing a shaped article containing
plant extract, which comprises a dispersion of the plant extract in a matrix
composed predominantly of a skeleton builder of hydrophilic macromolecules
selected from the group consisting of: collagen, gelatin, fractionated
gelatin, collagen hydrolysates, gelatin derivatives, elastin hydrolysates,
plant proteins, plant protein hydrolysates and mixtures thereof, wherein the
shaped article contains 0.1 to 98% by weight of said plant extract.
36. A food preparation containing a shaped article containing plant extract,
which comprises a dispersion of the plant extract in a matrix composed
predominantly of a skeleton builder of hydrophilic macromolecules selected
from the group consisting of: collagen, gelatin, fractionated gelatin,
collagen hydrolysates, gelatin derivatives, elastin hydrolysates, plant
proteins, plant protein hydrolysates and mixtures thereof, wherein the
shaped article contains 0.1 to 98% by weight of said plant extract.
37. A cosmetic product containing a shaped article containing plant extract,
which comprises a dispersion of the plant extract in a matrix composed
predominantly of a skeleton builder of hydrophilic macromolecules selected
from the group consisting of: collagen, gelatin, fractionated gelatin,
collagen hydrolysates, gelatin derivatives, elastin hydrolysates, plant
proteins, plant protein hydrolysates and mixtures thereof, wherein the
shaped article contains 0.1 to 98% by weight of said plant extract.
Description
The present invention relates to pellets or true spheres containing plant
extract(s) and which comprise a dispersion of the plant extract in a matrix
predominantly composed of a skeleton builder of a hydrophilic macromolecule.
The invention furthermore relates to a mild process for the preparation of
such pellets or true spheres and to their pharmaceutical, peroral or
cosmetic application.
The plant extract which is preferably employed is Aloe vera juice.
The plant extracts in the sense of the present invention are juices from
fresh plants obtained directly from the plant, pressed-out juices from fresh
plants, either in the original concentration or in concentrated form,
filtered and unfiltered, hydrophilic extracts (aqueous or alcoholic
extracts, for example ethanol extracts or 1,2-propylene glycol extracts)
such as, for example, original tinctures in homeopathy,
fluid extracts, macerates, lipophilic extracts (such as, for example, garlic
oil), essential oils, complete extracts or specifically standardized
extracts (for example standardized to a specific flavone glycoside content),
essential oil extracts, individually isolated plant constituents (such as,
for example, rutin), synthetic analogs (such as, for example, perfume oils,
camphor, thymol, vanillin) and derivatized plant constituents (such as, for
example, aglycones).
In individual cases, it is also possible to use dry extracts or the
redissolved extract from a dry extract in a suitable solvent, or decoctions
prepared therefrom. Pulverized drug constituents (for example leaves, roots,
herbaceous parts) can also be processed.
Being natural substances, plant extracts are frequently sensitive to
external factors such as light, oxidation by atmospheric oxygen, heat, pH
effects in solutions, or microbial contamination. In many plant-derived
active substances, it is known that only the fresh juice obtained originally
from the plant or parts thereof (for example Echinacea pressed-out juice or
Aloe vera juice) have optimum activity. Each means of preservation, such as
drying by heat, chemical preservation, heat treatment for preservation
purposes and the like adversely affect the delicate plant constituents with
regard to their chemical structure and thus their activity. In most cases,
preservation against microbial contamination is unavoidable when using fresh
plant juices so as to achieve at least limited shelf life.
In addition, the dry matter content of such fresh plant juices is very low,
and a large amount of water is being transported or stored.
Lipophilic plant extracts which are sensitive to oxidation, such as vitamin
E or garlic oil, are difficult to store in unaltered form and usually have
to be processed at once.
Essential oils are volatile and difficult to handle in the form of liquids.
Aloe vera (Aloe barbadensis Miller; synonyms: Aloe vera Tournefort et Linne,
Aloe vulgaris Lamarck) has been used for a long time in traditional medicine
of those regions in which this plant, which belongs to the family of the
Liliaceae grows wild.
If used externally, the gel-like plant juice has, for example, a beneficial
effect on wound healing, acts as an antibiotic or has a softening effect on
the skin.
Aloe vera juice can be administered internally in the treatment of gastric
diseases and disorders of the gastrointestinal tract. Anti-inflammatory
properties have also been reported.
These original findings have led to large plantations of Aloe vera having
been established in Central America, South America and parts of North
America. The juice in the leaves is obtained at the site itself in a
laborious process and subsequently concentrated under the mildest possible
conditions. The concentration of plant constituents in the freshly obtained
juice is between 0.3 and approximately 1%. Fresh Aloe vera fillets, aqueous
concentrates or spray- or freeze-dried goods are all commercially available.
The differences in quality of commercially available products are
considerable with regard to stability and composition and depend largely on
the preparation technology employed.
Aqueous concentrates or the juice from the leaves are currently being used
successfully in dermatoses (for example burns by the action of heat, UV rays
or X-rays), chemical burns, wounds, gastric diseases or parodontosis. It
appears that the pharmacological effect is only to be attributed to the
total of all constituents. A demonstration of the effect of individual
components is currently being investigated extensively.
However, since no undesired side-effects of Aloe vera juice are known, this
natural product has been offered for sale for many years in creams,
moisturizing emulsions, sun care products or for internal use.
The shelf life, or stability of storage, of the aqueous plant gel causes
substantial difficulties. Despite preservation, the liquid product is
unstable to the action of heat and pH, sensitive to oxygen and, moreover,
highly susceptible to microbial contamination.
The transport of fresh Aloe vera juice is difficult and costly due to the
high liquid volume--90-99% of water are transported--and the abovementioned
instability phenomena. Moreover, the juice must be cooled until it is used
in production. The preparation methods which involve the process steps
initial washing of the leaves, obtaining the fillets, homogenization,
purification and filtration, concentration and drying, can result in changes
in the constituents and bacterial contamination of the end product in
question if the technology used is unsuitable.
Aloe vera powders obtained by spray- or freeze-drying are only sparingly
redissolvable in cold water since they lack wettability and because there is
a danger of lump formation. Moreover, freeze-dried products are hygroscopic
and easily form lumps when stored inadequately. Commercially available
products which are readily dissolvable in water are frequently treated with
surfactants, which are undesired in cosmetics.
It is therefore an object of the invention to provide unpreserved,
storage-stable, concentrated, solid or semi-solid forms of plant extracts,
in particular of Aloe vera juice, which can be redissolved without problem
and whose pharmacological and cosmetic properties remain unaltered compared
with the native plant juice.
This object is achieved according to the invention by pellets containing
plant extract, which comprise a dispersion of the plant extract in a matrix
containing predominantly a skeleton builder of a hydrophilic macromolecule.
The following are employed as hydrophilic macromolecules: collagen, gelatin,
fractionated gelatin, collagen hydrolysates, gelatin derivatives, plant
proteins, plant protein hydrolysates, elastin hydrolysates; and mixtures of
the abovementioned substances.
This object is furthermore achieved by a process for the preparation of
pellets containing plant extract(s), which comprises mixing or emulsifying
the skeleton builder in solid or dissolved form with liquid plant extract,
or dissolving or suspending solid extracts in a solution of the skeleton
builder and making the product into shaped articles. If required, the shaped
articles can be dried. The only aspect that requires attention is that
matrix systems and active substance must not be incompatible.
In particular, the present invention provides shaped articles containing a
plant extract, which comprise a dispersion of the plant extract in a matrix
composed predominantly of a skeleton builder of hydrophilic macromolecules
selected from the group consisting of: collagen, gelatin, fractionated
gelatin, collagen hydrolysates, gelatin derivatives, elastin hydrolysates,
plant proteins, plant protein hydrolysates; and their mixtures.
The present invention furthermore provides a process for the preparation of
shaped articles containing plant extract, wherein
a) a skeleton builder of hydrophilic macromolecules selected from the group
consisting of: collagen, gelatin, fractionated gelatin, collagen
hydrolysates, gelatin derivatives, plant proteins, plant protein
hydrolysates, elastin hydrolysates; and their mixtures,
is mixed with plant extracts selected from the group consisting of:
hydrophilic liquid plant extracts, aqueous extracts, alcoholic extracts; and
their mixtures; and
b) the resulting mixture of skeleton builder and plant extract is added
dropwise to an intensely cold inert liquid, thus making it into shaped
articles.
Preferred embodiments of the invention are described and claimed in the
subclaims.
The following are examples of plant extracts or of extracts or individual
substances obtained therefrom: Flavonoids and their aglycones: rutin,
quercetin, diosmin, hyperoside, (neo)hesperidin, hesperitin, Ginkgo biloba
(for example ginkgo flavone glycosides), Crataegus extract (for example
oligomeric procyanidines), buckwheat (for example rutin), Sophora japonica
(for example rutin), birch leaves (for example quercetin glycosides,
hyperoside and rutin), elderflower (for example rutin), lime flower (for
example essential oil containing quercetin and farnesol), St John's wort oil
(for example olive oil extract), calendula, arnica (for example oily
extracts of the flowers with essential oil, polar extracts with flavonoids),
balm (for example flavones, essential oil),
Essential oils: sage (for example essential oil containing thymol), aniseed
(for example essential oil containing transanethol), oil of cloves (for
example essential oil containing eugenol), camomile (for example chamazulene,
alpha-bisabolol), myrtol: (limonene, alpha-pinene, cineol), oil of
peppermint (for example oil containing menthol), caraway (for example oil
containing carvone), dwarf pine oil (for example oil containing alpha-pinene),
juniper, rosemary, eucalyptus oil, lavender, fir leaf oil, bergamot oil,
citrus oil, balm, marjoram, thyme, basil (stomachic tonics or condiments),
fennel
Fatty oils: for example wheatgerm oil and vitamin E isolated therefrom, oil
of evening primrose (for example gammalinolenic acid), plant lecithins (for
example soybean lecithin), sphingolipids/ceramides isolated from plants
Immunostimulants: Echinacea purpurea (for example alcoholic extracts, fresh
plant juice, pressed-out juice), Eleutherococcus senticosus
Alkaloids: rauwolfia (for example prajmalin), periwinkle (for example
vincamin)
Other phytopharmaceuticals: aloe, horse chestnut (for example aescin),
garlic (for example garlic oil), pineapple (for example bromelains), ginseng
(for example ginsenosides), Our Lady's thistle fruit (for example extract
standardized with regard to silymarin), box holly root (for example
ruscogenin), valerian (for example valepotriates, Tct. Valerianae), kava
kava (for example kavalactones), hop flowers (for example hop bitters), Extr.
Passiflorae, gentian (for example ethanolic extract), anthraquinone-containing
drug extracts, for example aloin-containing Aloe vera juice, pollen extract,
extracts from algae, licorice extracts, palm extract, galphimia (for example
original tincture), mistletoe (for example aqueous ethanolic extract),
phytosterols (for example beta-sitosterin), verbascum (for example
aqueous-alcoholic extract), drosera (for example vinum liquorosum extract),
sea buckthorn fruit (for example juice obtained therefrom or sea buckthorn
oil), marshmallow root, primula root extract, fresh plant extracts of
mallow, comfrey, ivy, horsetail, yarrow, ribwort (for example pressed-out
juice), stinging nettle, greater celandine, parsley.
Plant extracts of Norolaena lobata, Tagetes lucida, Tecoma siems, Momordica
charantia.
As a rule, the plant extract is generally selected from the group consisting
of: solid plant extracts, liquid plant extracts, hydrophilic plant extracts,
lipophilic plant extracts, individual plant constituents; and mixtures of
these.
In general, the literature mentions Aloe vera juice, Aloe vera gel and Aloe
vera extracts. The term "Aloe vera juice" used in the sense of the
invention is to be understood as meaning, in general, the native juice
obtained directly from the leaf, the filtered or purified juice, the juice
which has been concentrated under mild conditions and also the redissolved
juice made of a dry extract. For internal use, it is also possible to use
the whole leaf, leaf constituents and flowers in homogenized form.
Alternatively, individual constituents may be suitable for specific uses.
The pellets according to the invention are spherical, uniform shaped
articles whose diameters have a customary range of 0.8-2 mm. Moreover, sizes
of 0.2-0.8 and 2-12 mm can be prepared according to the invention. Pellets
with a diameter of over 2 mm are termed true spheres in the present
invention, and they are suitable as single unit dosage form.
Surprisingly, the pellets display a great mechanical strength combined with
a low degree of abrasion (friability). They are storage-stable, can be
metered readily and are obtained as a free-flowing material due to the
specific preparation process. They can contain plant extract(s) at
concentrations of 0.1-98% (percent by weight), preferably 0.1-60%,
calculated as solids.
Surprisingly, neither the nature nor the composition of the constituents of
the native plant constituents are altered by the pellets according to the
invention. As a cold process, the process according to the invention is a
very mild form of processing. The pellets containing plant extract(s) can
exist in the form of a lyophilisate or in the form of solid or gel-like
pellets, depending on the preparation.
Preservatives or a heat treatment for preservation purposes can be dispensed
with by conversion into pellet form, using the matrix systems according to
the invention.
A pelleted fresh plant juice is storage-stable. If, for example, solvent
extraction is required for stability reasons, this can be dispensed with.
Furthermore, liquids can be converted into the solid form (essential oils or
fatty oils). This improves storage stability, transportability and the
handling quality of such substances.
The pellets, which have been dried conventionally according to the
invention, with or without addition of plasticizers, can be recognized
easily by their characteristic, typical appearance: they are transparent or
opalescent.
The product according to the invention can be employed directly for
pharmaceutical purposes, for internal use or for cosmetic purposes.
For pharmaceutical purposes, the pellets, as multiple unit dosage forms, can
be filled into sachets or hard gelatin capsules in the form of granules,
furthermore in the form of beverage granules for the preparation of drink
solutions (for example instant teas), and they can be packaged as single
unit dosage forms, i.e. single unit dose pellets for example filled into
suitable containers, blister packs or dosing dispensers for withdrawing them
singly. A further single unit form is represented by rapidly dissolving
tablets made by compressing freeze-dried pellets.
For cosmetic uses, it is particularly advantageous according to the
invention to use plant proteins or hydrolysates thereof, soluble collagen,
gelatin, collagen hydrolysates, elastin or elastin hydrolysates as carrier
materials of the shaped articles.
Gelatin is a scleroprotein obtained from collagen-containing material, and
its properties vary depending on the preparation process. It is composed
essentially of four molecular weight fractions which have an effect on
physicochemical properties as a function of the molecular weight and the
percentage by weight. For example, the more microgel (107 to 108 D) present,
the higher the viscosity of the aqueous solution. Commercially available
types contain up to 15 percent by weight. The fractions of alpha-gelatin and
the oligomers thereof (9.5.times.10.sup.4 /10.sup.5 to 10.sup.6 D) are
decisive for the solidity of the gel and they are conventionally between 10
and 40 percent by weight. Molecular weights below those of alpha-gelatin are
designated as peptides and can amount to up to 80 percent by weight in
conventional gelatin qualities (low Bloom value).
The sol/gel conversion behavior of gelatin, which depends on the molecular
composition, is a function of temperature and concentration. The Bloom value
is a conventional method for indicating the gelling capacity. Low commercial
qualities start at 50 Bloom, types with a high Bloom value have around 300
Bloom.
Fractionated gelatin is a specific type of gelatin and is obtained from
conventional gelatin by specific preparation processes, such as, for
example, ultrafiltration. The composition can be varied, for example, by
removing peptides (MW<9.5.times.10.sup.4 D) or by mixing individual
fractions, such as, for example, alphachains, dimeric and trimeric chains or
microgel.
Collagen in its native form is water-insoluble. Nowadays, specific
preparation processes allow soluble collagen types to be obtained.
Gelatin derivatives are chemically altered gelatins such as, for example,
succinylated gelatin, and these are also known as plasma expanders.
Collagen hydrolysate is to be understood as a collagen or gelatin product
which has no gelling capacity and which has been obtained by pressure
hydrolysis or enzymatically. The molecular weight composition can range
between a few hundred D up to below 9.5.times.10.sup.4 D, depending on the
preparation. Collagen hydrolysates are soluble in cold water.
For external use, these substances of biogenic origin are not only
distinguished by being well tolerated by the skin, they can also be
incorporated particularly easily into ointments, creams and emulsions. Here,
they display their specific property of acting somewhat as emulsifiers and
emulsion stabilizers. Thus, for example, the use of substantial amounts of
surfactants, which are skin irritants, can be reduced further, which
contributes to their tolerance by the skin, a demand which must be met by
pharmaceutical preparations, for example for the treatment of wounds, or by
modern cosmetics. Gelatin and collagen hydrolysates are pharmaceutically
recognized auxiliaries which are also preferably employed in the cosmetics
industry.
The plant proteins and the hydrolysates thereof are novel products whose
characteristics correspond largely to those of the collagen hydrolysates.
They are preferably obtained from wheat and soybeans and have molecular
weights of, for example, 200,000-300,000 D or 1000-10,000 D.
If plant proteins, plant protein hydrolysates or collagen hydrolysates
(gelatins which are soluble in cold water) or gelatins whose molecular
weight distribution has a maximum of some hundred D up to below 10.sup.5 D
are used, the lyophilized carrier material of the shaped articles according
to the invention, surprisingly, forms a highly-porous network structure
which is mechanically stable.
Elastin hydrolysates are obtained enzymatically from elastin and are
composed of a single polypeptide chain with a high proportion of non-polar
amino acids. They can be used in lipophilic systems due to their hydrophobic
properties. Elastin hydrolysates have a molecular weight of approximately
2000-3000 D and are strongly film-forming on the skin.
Rapid dissolution of the pellet formulae described is advantageous for
instant uses such as, for example, instant teas, instant drinks (for example
cough mixture), or instant creams without preservatives.
The recognized healing effect of fresh plant juices, for example Aloe vera
juice, on internal use (health care) can be improved advantageously by the
pellets according to the invention in the form of an instant preparation
without preservatives. If, for example, a fresh plant juice is cryopelleted
together with a rapidly dissolving matrix, storage-stable pellets are
obtained, and these (which are, for example, in sachets) can be dissolved
completely within a few seconds in water or fruit juices, milk or other
beverages. In addition, complete instant beverages can be advantageously
prepared according to the invention which are composed of fresh plant juice,
a matrix composition of proteins of biogenic origin (for example collagen
hydrolysates, wheat proteins) and natural skeleton builders, fruit juice
extract, honey and other natural components. Components of the matrix such
as, for example, gelatin, can mask unpleasant flavor, and glycerol and
sorbitol can act as sweeteners which are gentle on the teeth.
If the pellets according to the invention are not in lyophilized form, but
in solid or semi-solid form, they can be constructed advantageously of
sol/gel-forming hydrophilic macromolecules, such as, for example, gelatin or
fractionated gelatin, where the maximum of the molecular weight distribution
is above 10.sup.5 D and the consistency is a direct function of the nature
and concentration of the addition of plasticizer.
Such pellets which contain plasticizers are outstandingly suitable for
converting essential oils into a solid, and therefore readily processable,
form.
Semi-solid pellets, in particular, can be incorporated into the matrix in
such a manner that they melt or dissolve after application. Advantageous for
external use in the field of both pharmaceutics and cosmetics is the
gentleness on the skin of the matrix, which is composed of natural
substances.
The following text describes the process for the preparation of the pellets
according to the invention in greater detail.
More details in this context can be found in the parallel international
(PCT) applications listed hereinbelow. The contents of these parallel PCT
applications, which were filed at the German Patent Office on the same day
by the same inventors and applicants:
Internal file reference: P/81AL2741, title:
"Active-substance-containing solid articles having a skeleton of
hydrophilic macromolecules, and their preparation",
PCT/DE93/-00038=W093/13757, priorities claimed: German Patent Application P
42 01 179.5 dated Jan. 1, 1992, German Patent Application P 42 01 173.6
dated Jan. 1, 1992, U.S. Ser. No. 07/876,864 dated Apr. 30, 1992 and U.S.
Ser. No. 07/876,877 dated Apr. 30, 1992.
Internal file reference: P/81AL2742, title: "The preparation of
soft-gelatin capsules by a dripping process",
PCT/DE93/-00035=W093/13761, priorities claimed: German Patent Application P
42 01 178.7 dated Jan. 1, 1992 and U.S. Ser. No. 07/876,863 dated Apr. 30,
1992.
Internal file reference: P81AL2743, title: "Pellets containing
pharmaceutically active peptides, their preparation and their use"
PCT/DE93/00036=W093/13753, priorities claimed: German Patent Application P
42 01 179.5 dated Jan. 17, 1992 and U.S. Ser. No. 07/876,865.
In their entirety are herewith made a disclosure of the present application,
as are the earlier PCT applications: PCT/DE92/01010, PCT/DE92/01012,
PCT/DE92/01014, PCT/DE92/01016, PCT/DE92/01007, PCT/DE92/0 1008,
PCT/DE92/01015, PCT/DE92/01013, PCT/DE92/01009, PCT/DE92/01011 dated Dec. 4,
1992.
If the extract is aqueous, alcoholic or aqueous/alcoholic, the process
according to the invention for the preparation of pellets containing plant
extract(s) can be described by the following two process steps:
a) A skeleton builder of hydrophilic macromolecules from the group
consisting of: collagen, gelatin, fractionated gelatin, collagen
hydrolysates, gelatin derivatives, plant proteins, plant protein
hydrolysates and elastin hydrolysates, in solid or dissolved form, is mixed
with liquid, hydrophilic (aqueous, alcoholic or aqueous/alcoholic) plant
extract.
b) The resulting mixture of skeleton builder and liquid hydrophilic plant
extract is introduced dropwise into an intensely cold inert liquefied gas,
thus making shaped articles.
A shaped article in the sense of the invention is to be understood as one
selected from the group consisting of: powders, granules, pellets and
essentially symmetric aggregates.
In the description of the invention, characteristics, preparation and use
will be illustrated by way of preference with round pellets.
However, a person skilled in the art will also be able to employ other
shaped articles from the group consisting of: powders, granules and
essentially symmetric aggregates advantageously for the preparation of, in
particular, pharmaceutical formulations.
If, for example, collagen hydrolysates or plant protein hydrolysates which
are soluble in cold water are employed as skeleton builders, the process can
be carried out in the absence of heat, i.e. in the mildest manner possible.
In an embodiment of the process described under a), a composition which is
capable of forming drops, preferably composed of hydrophilic macromolecules
as skeleton builders, in particular plant proteins, plant protein
hydrolysates, collagen, gelatin, fractionated gelatin, collagen hydrolysates,
elastin hydrolysates or gelatin derivatives and aqueous, alcoholic or
aqueous/alcoholic plant extract is prepared.
First, the desired skeleton builder, in particular plant proteins, plant
protein hydrolysates, collagen, gelatin, fractionated gelatin, gelatin
derivatives or collagen hydrolysates, are dissolved either in the freshly
obtained or in the already concentrated, liquid aqueous, alcoholic or
aqueous/alcoholic plant extract, or the skeleton builder is already in
dissolved form and as such mixed with the plant extract, type and quantity
of the skeleton builder employed and, if appropriate, an addition of other
auxiliaries depending on the intended use of the pellets at a later point in
time. The concentration of the carrier material can range, for example, from
0.5 to 60% (w/w), preferably 0.5 to 30% (based on the composition to be
processed). If gelatin is employed, for example, then heat in a temperature
range of 30.degree. C. to 45.degree. C. may have to be used in order to
convert the gelatin into the sol form.
Furthermore, additives of the group consisting of: albumin, agar-agar, gum
arabic, pectins, tragacanth, xanthan, natural and modified starches,
dextrans, dextrins, maltodextrin, chitosan, alginates, cellulose
derivatives, polyvinylpyrrolidone, dextran, sugars, glycine, lactose,
mannitol, polyacrylic acid, methacrylic acid polymers, methacrylate
polymers, and their mixtures may be added at a concentration of 1-50%.
Further auxiliaries and carriers which are suitable for cosmetic, internal
or pharmaceutical application, such as, for example, additional skeleton
builders, which are described in greater detail further below, plasticizers
such as, for example, glycerol or sorbitol, fillers such as, for example,
lactose, dispersants such as, for example, disodium phosphate, pH regulators
such as, for example, disodium citrate, emulsifiers such as, for example,
lecithin, stabilizers such as, for example, ascorbic acid, cosolvents such
as, for example, polyethylene glycol, natural colorants such as, for
example, carotenoids, flavorings or masking flavors such as, for example,
fruit juice concentrates, may be added to this basic matrix.
In a further process variant, 1-50% (based on the composition to be
processed) of plasticizers selected from the group consisting of: glycerol,
propylene glycol, polyethylene glycols, triacetin, sorbitol, sorbitan
mixtures, sorbitol solutions, glucose syrup and other polyols or sugar
alcohols, and their mixtures may be added to the matrix.
Furthermore, it may be advantageous from the technological point of view to
add other skeleton-building substances to the formula in addition to the
skeleton builder of hydrophilic macromolecules.
Additional skeleton builders which can be employed are: albumins, agar-agar,
gum arabic, pectins, tragacanth, xanthan, natural and modified starches,
dextrans, dextrins, maltodextrin, chitosan, alginates, cellulose
derivatives, sugars, such as, for example, sucrose, glycine, lactose, PVP (polyvinylpyrrolidone),
mannitol and combinations of the abovementioned substances, but in
particular mannitol.
In the case of plant extracts which are exceedingly thermolabile, a further
embodiment of the invention surprisingly allows shaped articles to be
provided which have the characteristics according to the invention and which
have been prepared exclusively under cold conditions. In this procedure, a
matrix of a hydrophilic macromolecule is used which is selected from the
group consisting of: plant proteins, plant protein hydrolysates, elastin
hydrolysates, collagen hydrolysates, gelatin which is soluble in cold water,
gelatin derivatives; and mixtures of the abovementioned substances, whose
molecular weight distribution has a maximum of below 10.sup.5 D.
In an embodiment of the invention, additive substances may be selected from
this group so as to adapt the physical or chemical properties of the matrix
such as, for example, the viscosity, the mechanical strength or the
dissolution characteristics of the polymeric skeleton to suit the intended
use. Additions of dextrans, modified starches, sugars and, in particular,
mannitol, allow, for example, pellets to be prepared according to the
invention which dissolve in cold water spontaneously and completely.
Particularly suitable as additions of plasticizers are substances such as,
for example, sorbitol, which are solid at room temperature after drying.
Surprisingly, the matrix of such pellets forms a solid to semi-solid
structure after lyophilization which, when brought into contact with aqueous
medium or under physiological conditions, gives a bioadhesive and highly
viscous characteristic in the sense of the invention.
If solids, for example dry extracts, are processed, then they can be either
dissolved in the liquid matrix or suspended therein.
If liquid, lipophilic extracts (fatty or essential oils) are processed, then
they are emulsified in the liquid matrix. The surfactant properties of the
matrix constituents, such as, for example, gelatin or collagen hydrolysate,
can be utilized in an advantageous manner, so that, in many cases, the
process can be carried out without an addition of an emulsifier. This is a
considerable advantage when the product is administered perorally, but also
when it is used on sensitive or injured skin or in cosmetics. Microemulsions
mixed with the matrix may also be pelleted.
Fatty or essential oils which have been encapsulated by simple or complex
coacervation and essential oils which have been encapsulated by spray-drying
processes can be processed in the matrix according to the invention. It is
also possible to produce microcapsules or coacervates in the dissolved
matrix itself, and these microcapsules or coacervates together with the
matrix are then made into pellets which contain microcapsules incorporated
in the matrix. The same applies to nano-capsules.
For cosmetic purposes, it may furthermore be desired to add lipophilic
components, such as, for example, phospholipids, to the matrices described
so as to form liposomes.
In exceptional cases, the plant constituents themselves, in particular after
concentration, may act as skeleton builders for the preparation of pellets
according to the invention.
Of course, the mixtures according to the invention are suitable for
immediate decanting in liquid form by the process step as described under a)
to form containers, such as, for example, moldings, soft-gelatin capsules
and other suitable shells.
In an embodiment of the process step described under b), the matrix
described is immersed into a bath in the range of -108.degree. C. to
-210.degree. C. for rounding off (shaping) and shock frosting. The intensely
cold and inert liquid used is preferably liquid nitrogen, which does not
alter the constituents of the pellets. Round shaped articles (pellets) are
formed in the intensely cold liquid, and these form a mechanically stable
matrix after drying. Shaping is effected by a suitable dosing system. Each
discrete drop assumes the shape of a sphere, on the one hand as early as
during the free descent, on the other hand in the immersion bath due to the
gas layer which forms around it or the surface tension between system and
gas, whereupon freezing is completed. It is precisely this rapid, but yet
controllable freezing which fixes the given state of the system immediately,
i.e. no plant extract constituents can diffuse into the surrounding medium,
dissolved components can no longer crystallize, suspensions can no longer
sediment, emulsions cannot break, plant juice components which are sensitive
to high temperatures or moisture are cryopreserved, the carrier skeleton
cannot shrink and the like. The preparation process in which an inert liquid
gas is used therefore results in no adverse effects or alteration of the
product. Preservation of the desired characteristics is therefore
particularly advantageous. Moreover, the process is carried out in the
absence of solvents, does not pollute the environment and can be carried out
under sterile conditions.
Suitable dosing systems are all devices which are capable of producing
discrete, uniform drops whose size can be predetermined, for example
pipette-like dripping devices, or suitable spray or atomizing nozzles
equipped with dosing pumps.
Other devices which can be used for the process according to the invention
are dosing devices equipped with single-substance nozzles which expel the
material to be made into drops in a pulsed or intermittent fashion.
Another preferred embodiment of the process according to the invention
employs the "Cryopel" process (based on DE-OS 37 11 169) developed
by Messer Griesheim GmbH. With regard to the equipment used, scaling-up of
the process according to the invention to an industrial scale is
particularly simple in connection with an immersion frosting plant, the
CryopelR plant. This plant, which can be operated with liquid nitrogen, is
particularly distinguished by its economy. This plant is also suitable for
working under sterile conditions. A continuous operation which requires
little maintenance and cleaning allows an economical scaling-up of the
process according to the invention to an industrial scale.
FIG. 1 shows a diagram of the CryopelR process developed by Messer Griesheim
GmbH. From the heatable feeding device 1, the plant extract/matrix
composition according to the invention is added dropwise through metered
nozzles into the liquid nitrogen bath 3 at -196.degree. C. where it is made
into round pellets while simultaneously being subjected to shock frosting.
The frozen product is discharged via device 5 by means of the continuously
operating conveyor belt 2. The liquid nitrogen is metered via inlet pipe 7,
and the nitrogen gas formed escapes via pipe 6. The entire system is
enclosed by the insulation 4.
FIG. 2 shows a diagram of a process in which the plant extract/matrix
composition, which is either cold or heated at not more than 50.degree. C.,
is added dropwise continuously via a controllable dosing pump 8 through the
inlet pipe 9 and the heatable dropping nozzle 10 into the insulation trough
11, which contains liquid nitrogen 12. The shock-frosted pellets are
withdrawn batchwise. This device allows highly viscous compositions to be
processed.
If the system to be processed is not sufficiently flowable or not
sufficiently capable of forming drops, another 1-10% by weight of water can
be added, for example, or the processing temperature can be raised, or else
pressure may be used for the dosing operation. Analogously, a subatmospheric
pressure is to be applied in the opposite case (if the viscosity of the
system is too low). In this manner, a uniform formation as well as tearing
off of the individual droplets are guaranteed.
The processing temperature can vary within wide limits, but should be below
50.degree. C. in the case of specific plant extracts, such as, for example,
Aloe vera, to avoid thermal stress of the constituents.
Thus, a Cryopel dosing device allows compositions whose viscosity varies
within a wide range, for example 1.times.10.sup.-3 to 12.5 Pa.times.s
(Pascal seconds) to be dosed in a problem-free manner.
Other intensely cold liquids which are suitable for the process according to
the invention may be, for example, liquid rare gases, such as argon.
Depending on the dosing system selected, a particle size uniformity of over
70%, which can additionally be improved by grading, may be achieved.
Fractions removed by grading can be converted back into the liquid state and
repelleted, allowing the process to be carried out in a loss-free manner.
In an embodiment of the process step described, the pellets are dried, which
results in two process variants.
Variant A:
The pellets, which have been frozen at -196.degree. C., are introduced into
a freeze-drying plant. The temperatures selected are from 15.degree. C.
below the sublimation point of water at a pressure of 0.1 Pa to 103 Pa
(0.001 to 1.03 mbar). The drying process, which proceeds in a conventional
freeze-drying plant (condenser temperature -40.degree. C.) at -25.degree. C.
and 33 Pa (0.33 mbar) in primary drying with sublimation of the matrix
water, which has been frozen in amorphous form by means of shock-frosting,
results in an end product having a highly porous network structure after
secondary drying (desorption). In comparison with conventionally
freeze-dried goods, such pellets are particularly readily soluble and
preferably suitable for the development of instant preparations.
Variant B:
The frozen pellets are defrosted and conventionally dried. This process can
be carried out advantageously in vacuo (3000-5000 Pa (30-50 mbar)) to
accelerate the drying process and to maintain low temperatures. Drying
temperatures of up to 50.degree. C. may be selected, the temperature during
the drying process in the pellet matrix not rising to above 30.degree. C.
due to the evaporation enthalpy of the liquid.
In the case of conventionally dried pellets (variant B), sol/gel-forming
substances required for the matrix are those which are capable of forming
drops in sol form and which, after cryopelleting or defrosting, form a gel
which is stable after drying. An addition of plasticizers has a beneficial
effect on the formation of uniformly round shaped articles. Pellets which
have been prepared in this manner are distinguished by economical
preparation and can be employed both in the cosmetic and the pharmaceutical
sector.
Compared with the prior art, the process according to the invention itself
can be carried out, on the whole, with a low degree of maintenance and in an
economical fashion.
The pellets according to the invention can be suitable for pharmaceutical
purposes, but also peroral or cosmetic purposes.
The following are examples of pharmaceutical uses:
Peroral unit dosage form (2-12 mm pellets)
Pellets can also be filled directly into hard-gelatin capsules or sachets.
As a basis for the preparation of tablets, coated tablets and the like.
The pellets are outstandingly suitable for direct tabletting. The high
granulometric accuracy which can be achieved means that there are no dosing
problems.
Instant teas
In sachets, pellets can be offered for the preparation of health-care drink
solutions (instant preparation). If plant proteins, plant protein
hydrolysates, collagen hydrolysates or gelatin are used whose molecular
weight distribution has a maximum of some hundred D up to below 10.sup.5 D,
the pellets according to the invention dissolve in water at room temperature
in the course of a few seconds. Mixtures of a variety of plant extracts or
with other active substances are also possible in this form.
The combination of Aloe vera with pharmaceutically active substances, or
active substances in dietetics (health care), can furthermore contribute to
an improved tolerance of these substances, in particular when administered
internally. For example, irritation of the gastric mucosa by acetylsalicylic
acid can be reduced effectively by the constituents of the Aloe vera juice,
which have a protective action on the mucous membrane.
Balneotherapeutic products, inhalants for dissolution in hot water
Preparation of ointments, creams, gels and the like for the treatment of
wounds, for example in the case of burns and chemical burns and the like
Preparation of adhesive plasters and powders for use on wounds and the like
Pellets of active substance prepared under sterile conditions to be inserted
into wounds
The following are examples of cosmetic uses:
Preparation of creams, instant creams, moisturizing emulsions, sun care
products, products for use against solar dermatitis, shampoos, toothpastes,
soaps, bath products, facial toners
Direct use of pellets for the preparation of facial masks, powders and the
like
Use in cosmetics in the dissolved or semi-solid form
Use in cosmetics in combination with other active substances
Due to the high variability of the formulae and the preparation processes
described, the characteristics of the pellets according to the invention can
be adjusted in a very simple manner to suit the intended aim.
A specific matrix formation allows direct use of pellets in solid and
semi-solid form, dissolution being effected during application.
By varying the Bloom value of the gelatin employed according to the
invention it is not only possible to control characteristics such as, for
example, the dissolution rate of the pellets according to the invention, but
also to adjust a desired viscosity of an aqueous solution of these pellets,
again to suit the intended aim.
Such pellets have a series of advantages: the plant constituents remain
unaltered in unpreserved form compared with liquid extracts or dry extracts
prepared in the customary manner.
If plasticizers are added, they have an inimitable appearance and are,
moreover, very acceptable when ingested. Unpleasant flavor is already masked
by the matrix components themselves.
They allow an alcohol-free drug preparation for plant extracts to be
prepared or they can be employed as homoeopathic globuli. Compared with soft
gelatin capsules, the active substance cannot leak. Volatile essential oils
are formulated to give a solid preparation. In contrast to commercially
available solutions and tinctures, their weight is low, and they can be
swallowed easily as unit dosage forms.
The examples which follow are intended to illustrate the invention in
greater detail:
EXAMPLE 1
Pellets as a bath preparation for a medicinal bath against rheumatic
complaints (pharmaceutical application)
2.5 kg of gelatin, 150 Bloom
1.0 kg of glycerol
6.5 kg of water
375 g of juniper berry oil (essential oil)
The gelatin is allowed to pre-swell in the glycerol/water mixture at room
temperature for 30 minutes and is then dissolved at 60.degree. C. After the
essential oil of juniper berries has been added, the mixture is homogenized
in an Ultra-Turrax, and the emulsion formed is added dropwise to liquid
nitrogen at a temperature of -196.degree. C. via the dosing device shown in
FIG. 2. The pellets are dried in the air for 24 hours at 20.degree. C. and
filled into containers. 20 g of these pellets when added to a bath dissolve
completely in the warm water, releasing the essential oil. This gives a
medicinal bath against rheumatic complaints.
Also advantageous against muscular pain is a mixture of 10 g of these
pellets and 10 g of oil of rosemary pellets prepared in the same manner.
Melissa oil can be used to prepare a sedative bath.
To prepare pellets for inhalation, Oleum Pini Pumilionis is employed, and
the pellets are dissolved in hot water before inhalation.
EXAMPLE 2
Vitamin E emulsion pellets, freeze-dried for use in a protective cream
(cosmetic use)
0.15 kg of vitamin E obtained from wheatgerm oil
1.0 kg of collagen hydrolysate, molecular weight 13,000-18,000 g/mol
9 kg of water
The collagen hydrolysate is dissolved in water at room temperature, and the
liquid vitamin E is added while homogenizing in an Ultra-Turrax. The
resulting emulsion is added dropwise to liquid nitrogen at -196.degree. C.
via the dosing device as shown in FIG. 2 and shock-frosted in this manner.
The water is then removed from the pellets by freeze-drying.
The dried pellets are incorporated into the following protective cream as
"solid" vitamin E:
______________________________________
Lipid phase:
Tegomuls .RTM. 90S 2.5 kg
Soybean oil 5.0 kg
Cocoa butter 1.5 kg
Cetyl alcohol 1.5 kg
Aqueous phase:
Distilled water 3.0 kg
Active substance:
Vitamin E 30 g
______________________________________
which correspond to 230 g of vitamin E emulsion pellets The pellets are
emulsified with 1.8 l of water.
The components of the lipid phase are melted at 65.degree. C., and mixed
with 12 kg of the water, which has been heated to the same temperature, with
stirring, until a homogeneous mixture has formed. After the cream has cooled
to 30.degree. C., the vitamin E/collagen hydrolysate emulsion is stirred in.
EXAMPLE 3
Echinacea pellets, unit doage form
______________________________________
Original echinacea tincture
2.16 kg
______________________________________
Collagen hydrolysate, mean molecular weight 3000 g/mol 0.50 kg
______________________________________
Distilled water 0.50 kg
______________________________________
The collagen hydrolysate is dissolved in water at room temperature and the
solution is mixed with the original tincture. The ethanol is removed from
the ethanol/water mixture at 40.degree. C. under a vacuum of 5000 Pa (50
mbar) in a one-step vacuum evaporator.
The echinacea-containing solution is added dropwise to liquid nitrogen at
-196.degree. C. via a dosing device as shown in FIG. 2, giving the pellets.
These pellets are subsequently subjected to freeze-drying with a primary
drying step at -50.degree. C. and 5 Pa (0.05 mbar) and a secondary drying
step at 22.degree. C.
After drying, the echinacea pellets have a diameter of 5 mm. 3.times.1
pellets taken everyday corresponds to the dosage as a prophylactic against
common colds.
EXAMPLE 4
Echinacea soft gelatin pellets:
______________________________________
Gelatin (140 Bloom)
250 g
Glycerol 100 g
______________________________________
The gelatin is allowed to swell for 30 minutes in the mixture of fresh plant
juice and glycerol, this mixture is heated to 40.degree. C., and such an
amount of water that the composition is still flowable is removed under a
vacuum at 5000 Pa (50 mbar) in a one-step evaporator at 40.degree. C. The
composition is cryopelleted as in Example 1 via a dosing device as shown in
FIG. 2 and the pellets are dried under the conditions indicated. The
pellets, which have a diameter of 3.5 mm, are filled into a dosing
dispenser. A unit dose of 5 pellets is withdrawn for use as a prophylactic.
EXAMPLE 5
Rutin suspension
______________________________________
Gelatin 140 Bloom 200 g
Glycerol 150 g
Distilled water 650 g
Rutin 87.5 g
______________________________________
A solution is prepared from gelatin, glycerol and water as described in
Example 1, and the rutin is suspended in powder form. Pelleting and drying
is effected as shown in Example 1. 5 pellets of diameter 3.5 mm contain a
dose of 50 mg of rutin.
EXAMPLE 6
Aloe vera juice
150 g of collagen hydrolysate, mean molecular weight: 3000 g/mol
3000 g of Aloe vera juice, solids concentration 0.6% (w/w)
Freshly obtained fillets of Aloe vera leaves are homogenized, and the
product is purified and filtered. The collagen hydrolysate is dissolved,
with stirring, in the resulting, cooled Aloe vera juice. This solution is
then used for forming pellets at -196.degree. C. in an immersion bath
containing liquid nitrogen, using the Cryopel.sup.R feeding device.
The shock-frosted, round shaped articles are dried in a freeze-drying plant
where the primary drying step is carried out at -50.degree. C. and 5 Pa
(0.05 mbar) and the secondary drying step at 22.degree. C.
This gives pellets of diameter 4 mm and an Aloe vera content of 10.7% (w/w,
dry matter). Grading shows a granulometric accuracy of 78%.
The pellets dissolve completely in water at room temperature in the course
of 20 seconds.
EXAMPLE 7
100 g of collagen hydrolysate, mean molecular weight: 3000 g/mol
50 g of mannitol
50 g of wheat protein hydrolysate, molecular weight<5000 g/mol
2000 g of Aloe vera juice, solids concentration 0.6%
The collagen hydrolysate, the wheat protein hydrolysate and the mannitol are
dissolved in the cold Aloe vera juice, which has been processed as shown in
Example 6, and pellets are prepared as shown in Example 6. This gives
pellets of diameter 3 mm and an Aloe vera solids content of 5.7% (w/w).
Dissolved in orange juice or passion fruit juice, these pellets can be used
as a drink solution.
EXAMPLE 8
200 g of collagen hydrolysate, mean molecular weight: 3000 g/mol
4000 g of Aloe vera juice, 10.times.concentrate
The Aloe vera juice obtained in Example 6 is brought to a concentration of
10.times.at 40.degree. C. under a vacuum of 5000 Pa (50 mbar) by means of a
one-step vacuum evaporator. The collagen hydrolysate is dissolved in the
juice, and lyophilized pellets are prepared after short-term pasteurization.
Round shaped articles of diameter 4.5 mm and an Aloe vera solids content of
54.5% (w/w) are obtained.
The pellets dissolve in water at room temperature in the course of 40
seconds.
5 g of these pellets dissolved in 100 ml of sterile water give an effective
instant formula against solar dermatitis.
EXAMPLE 9
Incorporation of the pellets according to the invention into a night cream
a) Preparation of the pellets
300 g of collagen hydrolysate, mean molecular weight: 13,000-18,000 g/mol
4000 g of Aloe vera juice, solids concentration 0.6%
Lyophilized pellets with an Aloe vera solids content of 7.4% (w/w) are
prepared as described in Example 6.
b) Night cream formula
Lipid phase:
200 g of Tegomuls 90S
750 g of avocado oil
Aqueous phase:
200 g of native collagen (3% solution, molecular weight 300,000 g/mol)
30 g of elastin
32 g of Aloe vera pellets as described under a)
3000 g of freshly distilled water
The lipid phase is melted at 70.degree. C. The water is also heated to
70.degree. C. and the elastin is dissolved therein. The resulting aqueous
solution is homogenized in the lipid phase. The cream base is cooled to
35.degree. C. The Aloe vera pellets are dissolved in the cold collagen
solution and dispersed homogeneously in the cream base.
EXAMPLE 10
400 g of commercially available gelatin (170 Bloom)
300 g of glycerol (85%)
1300 g of Aloe vera juice, solids concentration 0.5% (w/w)
The gelatin powder is added to the freshly obtained and homogenized Aloe
vera juice and allowed to pre-swell for approximately 45 minutes. The
mixture is subsequently dissolved completely at 40.degree. C. and the
glycerol is admixed to give a homogeneous mixture.
The solution, which has a temperature of 40.degree. C., is subsequently
dosed into the immersion bath containing liquid nitrogen via the pump in the
plant shown in FIG. 2, and pellets are made. The deep-frozen, round shaped
articles are defrosted and dried at a rising temperature at between
25.degree. C. and 40.degree. C. The pellets have a residual moisture content
of 10% and are storage-stable.
The pellets which have been prepared in this manner can be incorporated into
a commercially available hydrogel (for example polyacrylate gel). The
pellets swell in the hydrogel after 10 to 15 minutes up to twice their
original size and form gel-like, readily meltable shaped articles which
dissolve after application to the skin.
Alternatively, the pellets can also be added directly to the hydrogel
without drying and without intermediate storage.
* * * * *
